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Acteoside is a bioactive phenylethanoid glycoside widely distributed throughout the plant kingdom. Because of its two catechol moieties, acteoside displays a variety of beneficial activities. The biosynthetic pathway of acteoside has been largely elucidated, but the assembly logic of two catechol moieties in acteoside remains unclear. Here, we identified a novel polyphenol oxidase OfPPO2 from Osmanthus fragrans, which could hydroxylate various monophenolic substrates, including tyrosine, tyrosol, tyramine, 4-hydroxyphenylacetaldehyde, salidroside, and osmanthuside A, leading to the formation of corresponding catechol-containing intermediates for acteoside biosynthesis. OfPPO2 could also convert osmanthuside B into acteoside, creating catechol moieties directly via post-modification of the acteoside skeleton. The reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis and subcellular localization assay further support the involvement of OfPPO2 in acteoside biosynthesis in planta. These findings suggest that the biosynthesis of acteoside in O. fragrans may follow "parallel routes" rather than the conventionally considered linear route. In support of this hypothesis, the glycosyltransferase OfUGT and the acyltransferase OfAT could direct the flux of diphenolic intermediates generated by OfPPO2 into acteoside. Significantly, OfPPO2 and its orthologs constitute a functionally conserved enzyme family that evolved independently from other known biosynthetic enzymes of acteoside, implying that the substrate promiscuity of this PPO family may offer acteoside-producing plants alternative ways to synthesize acteoside. Overall, this work expands our understanding of parallel pathways plants may employ to efficiently synthesize acteoside, a strategy that may contribute to plants' adaptation to environmental challenges.
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Catecol Oxidase , Glucosídeos , Fenóis , Proteínas de Plantas , Catecol Oxidase/metabolismo , Catecol Oxidase/genética , Glucosídeos/metabolismo , Glucosídeos/biossíntese , Fenóis/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Vias Biossintéticas , Oleaceae/enzimologia , Oleaceae/genética , Oleaceae/metabolismo , Catecóis/metabolismo , Regulação da Expressão Gênica de Plantas , PolifenóisRESUMO
Buprofezin, a chitin synthesis inhibitor, is widely used to control several economically important insect crop pests. However, the overuse of buprofezin has led to the evolution of resistance and exposed off-target organisms present in agri-environments to this compound. As many as six different strains of bacteria isolated from these environments have been shown to degrade buprofezin. However, whether insects can acquire these buprofezin-degrading bacteria from soil and enhance their own resistance to buprofezin remains unknown. Here we show that field strains of the brown planthopper, Nilaparvata lugens, have acquired a symbiotic bacteria, occurring naturally in soil and water, that provides them with resistance to buprofezin. We isolated a symbiotic bacterium, Serratia marcescens (Bup_Serratia), from buprofezin-resistant N. lugens and showed it has the capacity to degrade buprofezin. Buprofezin-susceptible N. lugens inoculated with Bup_Serratia became resistant to buprofezin, while antibiotic-treated N. lugens became susceptible to this insecticide, confirming the important role of Bup_Serratia in resistance. Sequencing of the Bup_Serratia genome identified a suite of candidate genes involved in the degradation of buprofezin, that were upregulated upon exposure to buprofezin. Our findings demonstrate that S. marcescens, an opportunistic pathogen of humans, can metabolize the insecticide buprofezin and form a mutualistic relationship with N. lugens to enhance host resistance to buprofezin. These results provide new insight into the mechanisms underlying insecticide resistance and the interactions between bacteria, insects and insecticides in the environment. From an applied perspective they also have implications for the control of highly damaging crop pests.
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Hemípteros , Inseticidas , Animais , Humanos , Inseticidas/farmacologia , Inseticidas/metabolismo , Resistência a Inseticidas/genética , Hemípteros/metabolismo , Bactérias , SoloRESUMO
Lung adenocarcinoma is a major public health problem with the low 5-year survival rate (15%) among cancers. Aberrant alterations of meiotic genes, which have gained increased attention recently, might contribute to elevated tumor risks. However, systematic and comprehensive studies based on the relationship between meiotic genes and LUAD recurrence and treatment response are still lacking. In this manuscript, we first confirmed that the meiosis related prognostic model (MRPM) was strongly related to LUAD progression via LASSO-Cox regression analyses. Furthermore, we identified the role of PPP2R1A in LUAD, which showed more contributions to LUAD process compared with other meiotic genes in our prognostic model. Additionally, repression of PPP2R1A enhances cellular susceptibility to nelfinavir-induced apoptosis and pyroptosis. Collectively, our findings indicated that meiosis-related genes might be therapeutic targets in LUAD and provided crucial guidelines for LUAD clinical intervention.
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The study investigated the effectiveness of EDN1 and EDN3 cytokines in the differentiation of melanocytes from hESCs. The findings showed that 100 nM EDN1 was more effective in promoting hESC to CD117+/TYR+ melanoblasts compared to 100 nM EDN3. Additionally, maintaining melanoblasts is beneficial for preserving the ability to proliferate. The study found that 10 nM EDN1 helped maintain the proliferation of melanoblasts without over maturing them into melanocytes in the late stage of differentiation. Thus, using 100 nM EDN1 in the initial stage and 10 nM EDN1 in the late stage proved to be an efficient and cost-effective method for obtaining hESC-derived melanocytes. The preliminary results suggest that EDN1 promotes melanoblast formation during the initial differentiation stage through its binding to both the EDNRB receptor and EDNRA receptor. This study provides a valuable tool for studying the development of human melanocytes and modelling the biology of disease.
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Endotelina-1 , Células-Tronco Embrionárias Humanas , Humanos , Endotelina-1/metabolismo , Melanócitos/metabolismo , Diferenciação CelularRESUMO
BACKGROUND: Whether Transanal drainage tubes (TDTs) placement reduces the occurrence of anastomotic leakage (AL) after rectal cancer (RC) surgery remains controversial. Most existing meta-analyses rely on retrospective studies, while the prospective studies present an inadequate level of evidence. METHODS: A systematic review and meta-analysis of prospective studies on TDTs placement in RC patients after surgery was conducted. The main analysis index was the incidence of AL, Grade B AL, and Grade C AL, while secondary analysis index was the incidence of anastomotic bleeding, incision infection, and anastomotic stenosis. A comprehensive literature search was performed utilizing the databases Cochrane Library, Embase, PubMed, and Web of Science. We recorded Risk ratios (RRs) and 95% confidence intervals (CI) for each included study, and a fixed-effect model or random-effect model was used to investigate the correlation between TDTs placement and four outcomes after RC surgery. RESULTS: Seven studies (1774 participants, TDT 890 vs non-TDT 884) were considered eligible for quantitative synthesis and meta-analysis. The meta-analysis revealed that the incidence of AL was 9.3% (83/890) in the TDT group and 10.2% (90/884) in the non-TDT group. These disparities were found to lack statistical significance (P = 0.58). A comprehensive meta-analysis, comprising four studies involving a cumulative sample size of 1259 participants, revealed no discernible disparity in the occurrence of Grade B AL or Grade C AL between the TDT group and the non-TDT group (Grade B AL: TDT 34/631 vs non-TDT 26/628, P = 0.30; Grade C AL: TDT 11/631 vs non-TDT 27/628, P = 0.30). Similarly, the incidences of anastomotic bleeding (4 studies, 876 participants), incision infection (3studies, 713 participants), and anastomotic stenosis (2studies, 561 participants) were 5.5% (24/440), 8.1% (29/360), and 2.9% (8/280), respectively, in the TDT group, and 3.0% (13/436), 6.5% (23/353), and 3.9% (11/281), respectively, in the non-TDT group. These differences were also determined to lack statistical significance (P = 0.08, P = 0.43, P = 0.48, respectively). CONCLUSION: The placement of TDTs does not significantly affect the occurrence of AL, Grade B AL, and Grade C AL following surgery for rectal cancer. Additionally, TDTs placement does not be associated with increased complications such as anastomotic bleeding, incision infection, or anastomotic stenosis. TRIAL REGISTRATION: PROSPERO: CRD42023427914.
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Fístula Anastomótica , Drenagem , Neoplasias Retais , Humanos , Fístula Anastomótica/etiologia , Fístula Anastomótica/epidemiologia , Neoplasias Retais/cirurgia , Incidência , Drenagem/métodos , Canal Anal/cirurgiaRESUMO
INTRODUCTION: The association of serum sex hormone-binding globulin (SHBG) concentrations with dementia risk remains uncertain in middle-aged to older women. We examined associations of serum SHBG levels with incidence of all-cause dementia and its subtypes in middle-aged to older women from the large population-based UK Biobank cohort study. METHODS: Serum total SHBG levels were measured by immunoassay. The incidence of all-cause dementia and its subtypes was recorded. Cox proportional hazards models were used to calculate hazard ratios (HR) for main outcomes. RESULTS: Among 171,482 community-dwelling women (mean [SD] age was 59.9 [5.4] years, median follow-up of 11.8 years), 2,368 developed dementia, including 1,088 from Alzheimer's disease (AD), 451 from vascular dementia (VAD), and 1,609 from other dementia. After multivariable adjustments, higher serum SHBG levels were significantly associated with higher risks of all-cause dementia, AD, and other dementia (all p < 0.05). Compared to those in the lowest quartile of SHBG levels, participants in the highest quartile of SHBG levels had a higher risk of all-cause dementia (HR: 1.34; 95% confidence interval [CI]: 1.16-1.53), AD (HR: 1.32; 95% CI: 1.07-1.62), and other dementia (HR: 1.44; 95% CI: 1.21-1.70). However, this relationship was not significant for VAD (HR: 1.16; 95% CI: 0.86-1.56). CONCLUSION: These findings indicated that higher serum SHBG concentrations were independently associated with higher risks of incident all-cause dementia, as well as AD and other dementia among middle-aged to older women. No association was found for VAD.
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Doença de Alzheimer , Globulina de Ligação a Hormônio Sexual , Idoso , Pré-Escolar , Feminino , Humanos , Pessoa de Meia-Idade , Bancos de Espécimes Biológicos , Estudos de Coortes , Estudos Prospectivos , Fatores de Risco , Biobanco do Reino UnidoRESUMO
BACKGROUND: The cytoplasmic male sterility (CMS) of rice is caused by chimeric mitochondrial DNA (mtDNA) that is maternally inherited in the majority of multicellular organisms. Wild rice (Oryza rufipogon Griff.) has been regarded as the ancestral progenitor of Asian cultivated rice (Oryza sativa L.). To investigate the distribution of original CMS source, and explore the origin of gametophytic CMS gene, a total of 427 individuals with seventeen representative populations of O. rufipogon were collected in from Dongxiang of Jiangxi Province to Sanya of Hainan Province, China, for the PCR amplification of atp6, orfH79 and B-atp6-orfH79, respectively. RESULTS: The B-atp6-orfH79 and its variants (B-atp6-GSV) were detected in five among seventeen populations (i.e. HK, GZ, PS, TL and YJ) through PCR amplification, which could be divided into three haplotypes, i.e., BH1, BH2, and BH3. The BH2 haplotype was identical to B-atp6-orfH79, while the BH1 and BH3 were the novel haplotypes of B-atp6-GSV. Combined with the high-homology sequences in GenBank, a total of eighteen haplotypes have been revealed, only with ten haplotypes in orfH79 and its variants (GSV) that belong to three species (i.e. O. rufipogon, Oryza nivara and Oryza sativa). Enough haplotypes clearly demonstrated the uniform structural characteristics of the B-atp6-orfH79 as follows: except for the conserved sequence (671 bp) composed of B-atp6 (619 bp) and the downstream followed the B-atp6 (52 bp, DS), and GSV sequence, a rich variable sequence (VS, 176 bp) lies between the DS and GSV with five insertion or deletion and more than 30 single nucleotide polymorphism. Maximum likelihood analysis showed that eighteen haplotypes formed three clades with high support rate. The hierarchical analysis of molecular variance (AMOVA) indicated the occurrence of variation among all populations (FST = 1; P < 0.001), which implied that the chimeric structure occurred independently. Three haplotypes (i.e., H1, H2 and H3) were detected by the primer of orfH79, which were identical to the GVS in B-atp6-GVS structure, respectively. All seventeen haplotypes of the orfH79, belonged to six species based on our results and the existing references. Seven existed single nucleotide polymorphism in GSV section can be translated into eleven various amino acid sequences. CONCLUSIONS: Generally, this study, indicating that orfH79 was always accompanied by the B-atp6, not only provide two original CMS sources for rice breeding, but also confirm the uniform structure of B-atp-orfH79, which contribute to revealing the origin of rice gametophytic CMS genes, and the reason about frequent recombination of mitochondrial DNA.
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Oryza , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Mitocôndrias/metabolismo , Oryza/genética , Melhoramento VegetalRESUMO
PURPOSE: A meta-analysis study was performed to systematically assess the association between tea consumption and CRC risk. METHODS: Cochrane Library, Embase, PubMed, and Web of Science were retrieved to collect articles in English since 24 July 2023. Databases were searched and evaluated by two reviewers independently.We screened the literature based on inclusion and exclusion criteria. After determining the random effect model or fixed utility model based on a heterogeneity test, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS: We included fourteen articles in this meta-analysis. We analyzed the data using a random effect model to explore the association between tea consumption and CRC because of apparent heterogeneity (P < 0.001, I2 = 99.5%). The combined results of all tests showed that there is no statistically significant association between tea consumption and CRC risk (OR = 0.756, 95%CI = 0.470-1.215, P = 0.247). Subsequently, subgroup analysis and sensitivity analysis were performed. Excluding any single study, the overall results ranged from 0.73 (95%CI = 0.44-1.20) to 0.86 (95%CI = 0.53-1.40). It was determined that there was no significant publication bias between tea consumption and CRC risk (P = 0.064) by Egger's tests. CONCLUSIONS: The results indicated that tea consumption may not be significantly associated with the development of CRC. IMPLICATIONS OF KEY FINDINGS: Tea reduces colon cancer risk by 24%, but the estimate is uncertain. The actual effect on risk can range from a reduction of 51% to an increase of 18%, but regional and population differences may cause differences.
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Neoplasias do Colo , Pesquisa , Humanos , Bases de Dados Factuais , Chá/efeitos adversosRESUMO
Appreciation of the importance of Akkermansia muciniphila is growing, and it is becoming increasingly relevant to identify preventive and/or therapeutic solutions targeting gut-liver-brain axes for multiple diseases via Akkermansia muciniphila. In recent years, Akkermansia muciniphila and its components such as outer membrane proteins and extracellular vesicles have been known to ameliorate host metabolic health and intestinal homeostasis. However, the impacts of Akkermansia muciniphila on host health and disease are complex, as both potentially beneficial and adverse effects are mediated by Akkermansia muciniphila and its derivatives, and in some cases, these effects are dependent upon the host physiology microenvironment and the forms, genotypes, and strain sources of Akkermansia muciniphila. Therefore, this review aims to summarize the current knowledge of how Akkermansia muciniphila interacts with the host and influences host metabolic homeostasis and disease progression. Details of Akkermansia muciniphila will be discussed including its biological and genetic characteristics; biological functions including anti-obesity, anti-diabetes, anti-metabolic-syndrome, anti-inflammation, anti-aging, anti-neurodegenerative disease, and anti-cancer therapy functions; and strategies to elevate its abundance. Key events will be referred to in some specific disease states, and this knowledge should facilitate the identification of Akkermansia muciniphila-based probiotic therapy targeting multiple diseases via gut-liver-brain axes.
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Probióticos , Verrucomicrobia , Humanos , Verrucomicrobia/metabolismo , Homeostase , Progressão da Doença , Fígado , EncéfaloRESUMO
Bufonis Venenum, an animal medicinal material, is widely used for treating cardiovascular diseases and pain induced by rheumatics or malignant tumors. In view of the high activity and high toxicity, it is of great significance to pay attention to the quality control of Bufonis Venenum to ensure the safety and effectiveness of its preparations. China's drug standards involve 102 preparations(474 batch numbers) containing Bufonis Venenum approved for sale, including 14 preparations in the Chinese Pharmacopoeia(2020 edition) and 68 preparations in the standards issued by the Ministry of Health Drug Standard of the People's Republic of China. Bufonis Venenum is mostly used in pill and powder preparations in the form of raw powder, with the main functions of clearing heat, removing toxin, relieving swelling and pain, replenishing qi, activating blood, opening orifice, and awakening brain. Except the high level of quality control for Bufonis Venenum in the preparations in the Chinese Pharmacopoeia(2020 edition), the quality control standards of Bufonis Venenum in other preparations are low or even absent. Therefore, it is urgent to conduct research on the improvement of quality standards for the preparations containing Bufonis Venenum. This study retrieved the reports focusing on the quality evaluation and quality control of the preparations containing Bufonis Venenum from CNKI, PubMed, and Web of Science. Qualitative and quantitative analysis methods for 64 preparations containing Bufonis Venenum have been reported, mainly including thin-layer chromatography, HPLC fingerprint, and multi-component content determination. The index components mainly involved bufadienolides, such as gamabufalin, arenobufagin, bufotalin, bufalin, cinobufagin, and resibufogenin. According to the literature information, this paper suggests that attention should be paid to the correlations between the analysis methods and detection indexes of medicinal materials, decoction pieces and preparations, the monitoring of indole alkaloids, and the content uniformity inspection for further improving the quality standards for the preparations containing Bufonis Venenum.
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Bufanolídeos , Bufonidae , Animais , Humanos , Pós , Bufanolídeos/farmacologia , Controle de Qualidade , Cromatografia Líquida de Alta Pressão , Dor/tratamento farmacológicoRESUMO
Gtf2ird1 and Gtf2i are two transcription factors (TFs) among the 28 genes deleted in Williams syndrome, and prior mouse models of each TF show behavioral phenotypes. Here we identify their genomic binding sites in the developing brain and test for additive effects of their mutation on transcription and behavior. GTF2IRD1 binding targets were enriched for transcriptional and chromatin regulators and mediators of ubiquitination. GTF2I targets were enriched for signal transduction proteins, including regulators of phosphorylation and WNT. Both TFs are highly enriched at promoters, strongly overlap CTCF binding and topological associating domain boundaries and moderately overlap each other, suggesting epistatic effects. Shared TF targets are enriched for reactive oxygen species-responsive genes, synaptic proteins and transcription regulators such as chromatin modifiers, including a significant number of highly constrained genes and known ASD genes. We next used single and double mutants to test whether mutating both TFs will modify transcriptional and behavioral phenotypes of single Gtf2ird1 mutants, though with the caveat that our Gtf2ird1 mutants, like others previously reported, do produce low levels of a truncated protein product. Despite little difference in DNA binding and transcriptome-wide expression, homozygous Gtf2ird1 mutation caused balance, marble burying and conditioned fear phenotypes. However, mutating Gtf2i in addition to Gtf2ird1 did not further modify transcriptomic or most behavioral phenotypes, suggesting Gtf2ird1 mutation alone was sufficient for the observed phenotypes.
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Fator de Ligação a CCCTC/genética , Proteínas Musculares/genética , Transativadores/genética , Fatores de Transcrição TFII/genética , Síndrome de Williams/genética , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Sistemas CRISPR-Cas/genética , Proteínas de Ligação a DNA/genética , Modelos Animais de Doenças , Desenvolvimento Embrionário/genética , Edição de Genes , Regulação da Expressão Gênica no Desenvolvimento/genética , Humanos , Camundongos , Transcrição Gênica/genética , Síndrome de Williams/patologiaRESUMO
BACKGROUND: The aim of the present study is to increase the solubility of dihydroartemisinin (DHA) using the self-emulsifying drug delivery system (SEDDS). METHODS: We first conducted solubility test and ternary phase diagram, then, in order to optimize the formulation of the DHA self-emulsifying agent, the design mixture method was selected in the design expert software. Next, optimal prescription validation and preliminary formulation evaluation were conducted. By comparing the oil-water partition coefficient in vitro, the improvement of the in vivo osmotic absorption of DHA via self-emulsification was evaluated. RESULTS: The optimal prescription ratio of oleic acid polyethylene glycol glyceride, polyoxyethylene hydrogenated castor oil, and diethylene glycol monoethyl ether in the DHA self-emulsifying preparation = 0.511:0.2:0.289 (w/w/w), with a drug-loading capacity of 26.3634 mg/g, solubility of 2.5448 mg/ml, and self-emulsification time of 230 s. The solubility self-emulsification was approximately 20.52 × higher in DHA than in the crude drug. The self-emulsification could improve DHA permeability and promoting in vivo DHA absorption. CONCLUSION: The DHA SEDDS could significantly improve DHA solubility and in vivo absorption.
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Sistemas de Liberação de Medicamentos , Polietilenoglicóis , Artemisininas , Solubilidade , ÁguaRESUMO
SUMMARY: Whole genome sequencing of patient populations is identifying thousands of new variants in untranslated regions (UTRs). While the consequences of UTR mutations are not as easily predicted from primary sequence as coding mutations are, there are some known features of UTRs that modulate their function. utr.annotation is an R package that can be used to annotate potential deleterious variants in the UTR regions for both human and mouse species. Given a CSV or VCF format variant file, utr.annotation provides information of each variant on whether and how it alters known translational regulators including upstream open reading frames, upstream Kozak sequences, polyA signals, Kozak sequences at the annotated translation start site, start codons and stop codons, conservation scores in the variant position, and whether and how it changes ribosome loading based on a model derived from empirical data. AVAILABILITY AND IMPLEMENTATION: utr.annotation is freely available on Bitbucket (https://bitbucket.org/jdlabteam/utr.annotation/src/master/) and CRAN (https://cran.r-project.org/web/packages/utr.annotation/index.html). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Regulação da Expressão Gênica , Genômica , Camundongos , Humanos , Animais , Regiões não TraduzidasRESUMO
In this work, an adaptive liquid lens using a novel transparent electrically responsive fluid, dibutyl adipate (DBA), is demonstrated. The DBA liquid lens with a hemispherical plano-convex shape can change its curvature according to the application of various input voltages. More specifically, when an external direct current (DC) electric field is applied to the DBA liquid, the charges that are injected from the cathode move along with the DBA molecules toward the anode and accumulate on the surface of the anode. When the DC electric field is removed, the shape of the DBA liquid is recovered to its original state. This electrostatic force induces the deformation of the DBA liquid lens within a concentric annular anode electrode. In addition, the focal length of our system is increased from a value of approximately 7.5â mm to 13.1â mm when the voltage is changed from 0 to 100â V. Interestingly, the resolution of our DBA liquid lens can reach a value of â¼28.5 lp/mm. The proposed DBA liquid lens exhibits high optical transmittance (â¼95%), good thermal stability (20-100°C), simple structure, and an excellent imaging property, which implies that the DBA liquid is a promising candidate for fabricating novel adaptive liquid lenses.
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Germ cell tumor is the most common malignant tumor of the gonads, sometimes they are found in locations other than the gonads, called Extra-gonadal Germ cell tumours (EGCTs). Primary mediastinal germ cell tumors (PMGCTs) are a kind of rare neoplasm in the anterior mediastinum, including seminoma and non-seminomatous, or appear as a mixture. Primary mediastinal seminoma mixed with sarcoma is an extremely rare clinicopathologic entity. Previous studies have revealed that primary pure mediastinal seminomas are commonly sensitive to chemoradiotherapy and possibly to palliative excision. The treatment options for mixed germ cell tumor composed of seminoma and sarcoma remain unknown. Only one case of primary mediastinal seminoma with rhabdosarcoma has been reported in the literature up to date and the patient benefited from chemotherapy as the neoadjuvant therapy. However, cases of primary mediastinal seminoma with leiomyosarcoma have not been documented. Herein, we report a case of an 18-year-old patient, who presented with dyspnea, orthopnea, and chest pain, the CECT scan of the chest showed a large mass in the anterior mediastinum, which turned out to be seminoma mixed with leiomyosarcoma after partial excision. We investigate the treatment strategy and potential molecular mechanism of this disease. Finally, our study demonstrated that the patient benefited from the treatment of chemotherapy alone, or combined with target therapy after the operation. Meanwhile, the BRAF p.G466V, TP53 mutations, MTOR p.T1977I and exons 2-5 deletion of FLCN may be potential molecular mechanisms and oncogenic drivers of this disease.
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Leiomiossarcoma , Neoplasias do Mediastino , Neoplasias Embrionárias de Células Germinativas , Seminoma , Neoplasias Testiculares , Adolescente , Humanos , Leiomiossarcoma/diagnóstico , Leiomiossarcoma/genética , Masculino , Neoplasias do Mediastino/tratamento farmacológico , Neoplasias do Mediastino/terapia , Mediastino/patologia , Seminoma/patologia , Seminoma/cirurgia , Neoplasias Testiculares/patologiaRESUMO
Ferroptosis is primarily caused by intracellular iron catalytic activity and lipid peroxidation. The potential interplay between ferroptosis and apoptosis remains poorly understood. Here, we show that the expression of a nuclear long non-coding RNA (lncRNA), LINC00618, is reduced in human leukemia and strongly increased by vincristine (VCR) treatment. Furthermore, LINC00618 promotes apoptosis by increasing the levels of BCL2-Associated X (BAX) and cleavage of caspase-3. LINC00618 also accelerates ferroptosis by increasing the levels of lipid reactive oxygen species (ROS) and iron, two surrogate markers of ferroptosis, and decreasing the expression of solute carrier family 7 member 11 (SLC7A11). Interestingly, VCR-induced ferroptosis and apoptosis are promoted by LINC00618, and LINC00618 accelerates ferroptosis in a manner dependent upon apoptosis. LINC00618 attenuates the expression of lymphoid-specific helicase (LSH), and LSH enhances the transcription of SLC7A11 after the recruitment to the promoter regions of SLC7A11, further inhibiting ferroptosis. Knowledge of these mechanisms demonstrates that lncRNAs related to ferroptosis and apoptosis are critical to leukemogenesis and chemotherapy.
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Apoptose/genética , Ferroptose/genética , RNA Longo não Codificante/genética , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Biomarcadores Tumorais , Linhagem Celular Tumoral , Núcleo Celular , Ferroptose/efeitos dos fármacos , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Ligação Proteica , Espécies Reativas de Oxigênio/metabolismoRESUMO
A transparent fluid dibutyl adipate (DBA) is suitable for fabricating the adaptive lens due to its unique deformation under a direct current (DC) electric field. In this report, a DBA liquid microlens array (LMA) with a tunable focal length is demonstrated. A hydrophobic layer deposited in the ring array patterns on the electrode induced the formation of the DBA liquid microdroplets array self-assembly. The electronegative DBA liquid tends to move to the anode at a DC voltage. The proposed DBA LMA with a diameter of 100 µm can change its focal length from 0.92 to 1.42 mm when the voltage changes from 0 to 200 V. The response time is relatively fast (â¼790m s). Due to the high optical transmittance (â¼91%) and good thermal stability in the temperature range of -24.8-161.5∘C, our DBA LMA shows good focusing properties and has potential applications in the field of image processing, portable electronic devices, beam steering, ophthalmology, and 3D displays.
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Nickel-based superalloys are widely used in key hot-end components such as aero engines and industrial gas turbines due to their excellent comprehensive properties. Real-time monitoring of engine blades and other structures in high-temperature environments can promptly discover possible internal damage to the structure. Optical fiber sensing technology has unique advantages that traditional electrical sensors do not have, such as anti-electromagnetic interference, small size, light weight, and corrosion resistance. The technology is gradually replacing traditional methods and becoming an important means of structural health monitoring. We propose an optical fiber sensor and assembly method that can be used to measure the strain of a nickel-based directionally solidified superalloy in a high-temperature environment more accurately. The proposed technology is simple to manufacture and also has low cost and a high survival rate, which is of great significance for high-temperature strain measurements in aerospace and other fields.
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Bioactive polysaccharides from natural resources target various biological processes and are increasingly used as potential target molecules for drug development. However, the accessibility of branched and long complex polysaccharide active domains with well-defined structures remains a major challenge. Herein we describe an efficient first total synthesis of a highly branched heptadecasaccharide moiety of the native bioactive galectin-3-targeting polysaccharide from Carthamus tinctorius L. as well as shorter fragments of the heptadecasaccharide. The key feature of the approach is that a photo-assisted convergent [6+4+7] one-pot coupling strategy enables rapid assembly of the heptadecasaccharide, whereby a photoremovable o-nitrobenzyl protecting group is used to generate the corresponding acceptor for glycosylation in situ upon ultraviolet radiation. Biological activity tests suggest that the heptadecasaccharide can target galectin-3 and inhibit pancreatic cancer cell growth.
Assuntos
Carthamus tinctorius , Neoplasias , Carthamus tinctorius/química , Galectina 3 , Glicosilação , Polissacarídeos/farmacologia , Raios UltravioletaRESUMO
BACKGROUND: There is accumulating evidence to suggest that microRNAs (miRNAs) are associated with the progressive optic neuropathy including glaucoma. Apoptosis of retinal ganglion cells (RGCs) is a hallmark of glaucoma. The present study focused on the effects of miR-145-5p on RGC apoptosis in glaucoma. METHODS: We established a glaucoma rat model by intraocular injection of N-methyl-d-aspartic acid (NMDA). RGCs were isolated from newborn rats and treated with NMDA. Hematoxylin and eosin staining was performed to detect morphological changes in the retinas of rats. The expression of miR-145-5p and tripartite motif-containing 2 (TRIM2) in RGCs was measured by RT-qPCR. The viability of RGCs was measured by MTT assay. Flow cytometry analysis and TUNEL assays were conducted to assess the apoptosis of RGCs. The interaction between miR-145-5p and TRIM2 was investigated using a luciferase reporter assay. RESULTS: Rats injected with NMDA showed a thinner ganglion cell layer (GCL) and inner plexiform layer (IPL) as well as increased expression of miR-145-5p. Silencing of miR-145-5p significantly increased the GCL and IPL in the glaucoma rat model. Moreover, miR-145-5p expression was upregulated in RGCs ex vivo in response to NMDA. Silencing of miR-145-5p promoted cell viability and suppressed apoptosis in NMDA-treated RGCs. Mechanistically, miR-145-5p targeted the TRIM2 3' untranslated region to suppress its expression. TRIM2 was upregulated in NMDA-treated RGCs and protected RGCs against NMDA-induced apoptosis. Furthermore, miR-145-5p suppressed the PI3K/AKT pathway by downregulating TRIM2 in NMDA-treated RGCs. CONCLUSIONS: Suppression of miR-145-5p inhibited the apoptosis of RGCs via TRIM2-mediated activation of the PI3K/AKT signaling pathway in NMDA-induced glaucoma.