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Compressing the optical field to the atomic scale opens up possibilities for directly observing individual molecules, offering innovative imaging and research tools for both physical and life sciences. However, the diffraction limit imposes a fundamental constraint on how much the optical field can be compressed, based on the achievable photon momentum1,2. In contrast to dielectric structures, plasmonics offer superior field confinement by coupling the light field with the oscillations of free electrons in metals3-6. Nevertheless, plasmonics suffer from inherent ohmic loss, leading to heat generation, increased power consumption and limitations on the coherence time of plasmonic devices7,8. Here we propose and demonstrate singular dielectric nanolasers showing a mode volume that breaks the optical diffraction limit. Derived from Maxwell's equations, we discover that the electric-field singularity sustained in a dielectric bowtie nanoantenna originates from divergence of momentum. The singular dielectric nanolaser is constructed by integrating a dielectric bowtie nanoantenna into the centre of a twisted lattice nanocavity. The synergistic integration surpasses the diffraction limit, enabling the singular dielectric nanolaser to achieve an ultrasmall mode volume of about 0.0005 λ3 (λ, free-space wavelength), along with an exceptionally small feature size at the 1-nanometre scale. To fabricate the required dielectric bowtie nanoantenna with a single-nanometre gap, we develop a two-step process involving etching and atomic deposition. Our research showcases the ability to achieve atomic-scale field localization in laser devices, paving the way for ultra-precise measurements, super-resolution imaging, ultra-efficient computing and communication, and the exploration of light-matter interactions within the realm of extreme optical field localization.
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Miniaturized lasers play a central role in the infrastructure of modern information society. The breakthrough in laser miniaturization beyond the wavelength scale has opened up new opportunities for a wide range of applications1-4, as well as for investigating light-matter interactions in extreme-optical-field localization and lasing-mode engineering5-19. An ultimate objective of microscale laser research is to develop reconfigurable coherent nanolaser arrays that can simultaneously enhance information capacity and functionality. However, the absence of a suitable physical mechanism for reconfiguring nanolaser cavities hinders the demonstration of nanolasers in either a single cavity or a fixed array. Here we propose and demonstrate moiré nanolaser arrays based on optical flatbands in twisted photonic graphene lattices, in which coherent nanolasing is realized from a single nanocavity to reconfigurable arrays of nanocavities. We observe synchronized nanolaser arrays exhibiting high spatial and spectral coherence, across a range of distinct patterns, including P, K and U shapes and the Chinese characters '' and '' ('China' in Chinese). Moreover, we obtain nanolaser arrays that emit with spatially varying relative phases, allowing us to manipulate emission directions. Our work lays the foundation for the development of reconfigurable active devices that have potential applications in communication, LiDAR (light detection and ranging), optical computing and imaging.
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Adoptive transfer of antigen-specific T cells represents a major advance in cancer immunotherapy, with robust clinical outcomes in some patients1. Both the number of transferred T cells and their differentiation state are critical determinants of effective responses2,3. T cells can be expanded with T cell receptor (TCR)-mediated stimulation and interleukin-2, but this can lead to differentiation into effector T cells4,5 and lower therapeutic efficacy6, whereas maintenance of a more stem-cell-like state before adoptive transfer is beneficial7. Here we show that H9T, an engineered interleukin-2 partial agonist, promotes the expansion of CD8+ T cells without driving terminal differentiation. H9T led to altered STAT5 signalling and mediated distinctive downstream transcriptional, epigenetic and metabolic programs. In addition, H9T treatment sustained the expression of T cell transcription factor 1 (TCF-1) and promoted mitochondrial fitness, thereby facilitating the maintenance of a stem-cell-like state. Moreover, TCR-transgenic and chimeric antigen receptor-modified CD8+ T cells that were expanded with H9T showed robust anti-tumour activity in vivo in mouse models of melanoma and acute lymphoblastic leukaemia. Thus, engineering cytokine variants with distinctive properties is a promising strategy for creating new molecules with translational potential.
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Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Agonismo Parcial de Drogas , Interleucina-2/análogos & derivados , Interleucina-2/agonistas , Proteínas Mutantes/farmacologia , Células-Tronco/efeitos dos fármacos , Animais , Linfócitos T CD8-Positivos/imunologia , Interleucina-2/química , Interleucina-2/genética , Melanoma/metabolismo , Camundongos , Mitocôndrias/efeitos dos fármacos , Proteínas Mutantes/química , Proteínas Mutantes/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/metabolismo , Fator de Transcrição STAT5/metabolismo , Células-Tronco/citologia , Fator 1 de Transcrição de Linfócitos T/metabolismo , Pesquisa Translacional BiomédicaRESUMO
Plasmonics enables the manipulation of light beyond the optical diffraction limit1-4 and may therefore confer advantages in applications such as photonic devices5-7, optical cloaking8,9, biochemical sensing10,11 and super-resolution imaging12,13. However, the essential field-confinement capability of plasmonic devices is always accompanied by a parasitic Ohmic loss, which severely reduces their performance. Therefore, plasmonic materials (those with collective oscillations of electrons) with a lower loss than noble metals have long been sought14-16. Here we present stable sodium-based plasmonic devices with state-of-the-art performance at near-infrared wavelengths. We fabricated high-quality sodium films with electron relaxation times as long as 0.42 picoseconds using a thermo-assisted spin-coating process. A direct-waveguide experiment shows that the propagation length of surface plasmon polaritons supported at the sodium-quartz interface can reach 200 micrometres at near-infrared wavelengths. We further demonstrate a room-temperature sodium-based plasmonic nanolaser with a lasing threshold of 140 kilowatts per square centimetre, lower than values previously reported for plasmonic nanolasers at near-infrared wavelengths. These sodium-based plasmonic devices show stable performance under ambient conditions over a period of several months after packaging with epoxy. These results indicate that the performance of plasmonic devices can be greatly improved beyond that of devices using noble metals, with implications for applications in plasmonics, nanophotonics and metamaterials.
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Bacterial wilt (BW) caused by Ralstonia solanacearum is a globally prevalent bacterial soil-borne disease. In this study, transcriptome sequencing were subjected to roots after infection with the R. solanacearum in the resistant and susceptible tobacco variety. DEGs that responded to R. solanacearum infection in both resistant and susceptible tobacco contributed to pectinase and peroxidase development and were enriched in plant hormone signal transduction, signal transduction and MAPK signalling pathway KEGG terms. Core DEGs in the resistant tobacco response to R. solanacearum infection were enriched in cell wall, membrane, abscisic acid and ethylene terms. qRT-PCR indicated that Nitab4.5_0004899g0110, Nitab4.5_0004234g0080 and Nitab4.5_0001439g0050 contributed to the response to R. solanacearum infection in different resistant and susceptible tobacco. Silencing the p450 gene Nitab4.5_0001439g0050 reduced tobacco resistance to bacterial wilt. These results improve our understanding of the molecular mechanism of BW resistance in tobacco and solanaceous plants.
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Ralstonia solanacearum , Ralstonia solanacearum/genética , Perfilação da Expressão Gênica , Reguladores de Crescimento de Plantas/farmacologia , Ácido Abscísico , Nicotiana/genética , Inativação Gênica , Resistência à Doença/genéticaRESUMO
The TIFY gene family plays an essential role in plant development and abiotic and biotic stress responses. In this study, genome-wide identification of TIFY members in tobacco and their expression pattern analysis in response to Ralstonia solanacearum infection were performed. A total of 33 TIFY genes were identified, including the TIFY, PPD, ZIM&ZML and JAZ subfamilies. Promoter analysis results indicated that a quantity of light-response, drought-response, SA-response and JA-response cis-elements exist in promoter regions. The TIFY gene family exhibited expansion and possessed gene redundancy resulting from tobacco ploidy change. In addition, most NtTIFYs equivalently expressed in roots, stems and leaves, while NtTIFY1, NtTIFY4, NtTIFY18 and NtTIFY30 preferentially expressed in roots. The JAZ III clade showed significant expression changes after inoculation with R. solanacearum, and the expression of NtTIFY7 in resistant varieties, compared with susceptible varieties, was more stably induced. Furthermore, NtTIFY7-silenced plants, compared with the control plants, were more susceptible to bacterial wilt. These results lay a foundation for exploring the evolutionary history of TIFY gene family and revealing gene function of NtTIFYs in tobacco bacterial wilt resistance.
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Família Multigênica , Nicotiana , Doenças das Plantas , Proteínas de Plantas , Ralstonia solanacearum , Ralstonia solanacearum/genética , Nicotiana/genética , Nicotiana/microbiologia , Nicotiana/metabolismo , Doenças das Plantas/microbiologia , Doenças das Plantas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Resistência à Doença/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Filogenia , Regiões Promotoras GenéticasRESUMO
BACKGROUND: Lenvatinib is approved as a first-line treatment for patients with unresectable and/or recurrent hepatocellular carcinoma (HCC). Lenvatinib achieved promising clinical benefits in REFLECT but was associated with clinically significant treatment-emergent hypertension (CSTE-HTN, a grouped term), a common class effect of tyrosine kinase inhibitors. This post hoc analysis assessed the impact of CSTE-HTN on the efficacy and safety of lenvatinib in HCC. METHODS: Patients from REFLECT who received lenvatinib (n = 476) were stratified according to CSTE-HTN. Tumors were assessed by mRECIST. Overall survival (OS) and progression-free survival (PFS) were evaluated using landmark analyses at 4 and 8 weeks. RESULTS: A total of 212 patients in the lenvatinib arm developed CSTE-HTN, and 264 did not. CSTE-HTN first occurred at 3.7 weeks (median); the worst grade CSTE-HTN occurred at 4.1 weeks (median). No patients had life-threatening CSTE-HTN and/or died due to CSTE-HTN. Median OS was numerically longer in patients with versus without CSTE-HTN (at 4 weeks: 16.3 vs. 11.6 months; hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.621-1.004; at 8 weeks: 13.5 vs. 11.6 months; HR, 0.87; 95% CI, 0.696-1.089). Median PFS was similar between patients with and without CSTE-HTN (at 4 weeks: 6.6 vs. 6.4 months; HR, 0.887; 95% CI, 0.680-1.157; at 8 weeks: 5.7 vs. 6.4 months; HR, 1.09; 95% CI, 0.84-1.41). Objective response rate was numerically higher in patients with (48.6%) versus without CSTE-HTN (34.5%). CONCLUSIONS: In this retrospective analysis, CSTE-HTN was associated with improved OS but not PFS. CSTE-HTN did not impair the outcomes of patients with HCC treated with lenvatinib when detected early and managed appropriately.
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Carcinoma Hepatocelular , Hipertensão , Neoplasias Hepáticas , Compostos de Fenilureia , Quinolinas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Estudos Retrospectivos , Neoplasias Hepáticas/tratamento farmacológico , Hipertensão/induzido quimicamente , Hipertensão/complicações , Hipertensão/tratamento farmacológicoRESUMO
BACKGROUND: Reperfusion is the most effective strategy for myocardial infarct, but induces additional injury. WD repeat and SOCS box containing protein 1 (WSB1) plays a protective role in ischemic cells. This study aims to investigate the effects of WSB1 on myocardial ischemia-reperfusion (IR) injury. METHODS: The myocardial IR was induced by left anterior descending (LAD) ligation for 45 min and subsequent reperfusion. The overexpression of WSB1 was mediated by tail vein injection of AAV9 loaded with WSB1 encoding sequence two weeks before IR surgery. H9c2 myocardial cells underwent oxygen-sugar deprivation/reperfusion (OGD/R) to mimic IR, and transfected with WSB1 overexpression or silencing plasmid to alter the expression of WSB1. RESULTS: WSB1 was found highly expressed in penumbra of myocardial IR rats, and the WSB1 overexpression relieved IR-induced cardio dysfunction, myocardial infarct and pathological damage, and cardiomyocyte death in penumbra. The ectopic expression of WSB1 in H9c2 myocardial cells mitigated OGD/R-caused apoptosis, and silencing of WSB1 exacerbated the apoptosis. In addition, WSB1 activated ß-catenin signaling, which was deactivated under the ischemic condition. The co-immunoprecipitation results revealed that WSB1 mediated ubiquitination and degradation of glycogen synthase kinase 3 beta (GSK3ß) as an E3 ligase in myocardial cells. The effects of WSB1 on myocardial cells under ischemic conditions were abolished by an inhibitor of ß-catenin signaling. CONCLUSION: WSB1 activated ß-catenin pathway by promoting the ubiquitination of GSK3ß, and restrained IR-induced myocardial injury. These findings might provide novel insights for clinical treatment of myocardial ischemic patients.
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Peptídeos e Proteínas de Sinalização Intracelular , Infarto do Miocárdio , Traumatismo por Reperfusão Miocárdica , Animais , Humanos , Ratos , Apoptose , beta Catenina/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Infarto do Miocárdio/metabolismo , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/metabolismo , Miócitos Cardíacos/metabolismo , Ubiquitina-Proteína Ligases , UbiquitinaçãoRESUMO
OBJECTIVES: A classification system of ovarian ectopic pregnancies (OEP) could aid in their management. This study aimed to investigate the ultrasound classification and preoperative ultrasound diagnosis of OEP. METHODS: This retrospective case series study analyzed the clinical and ultrasound imaging data of 68 pregnant women diagnosed and confirmed with OEP at the Obstetrics and Gynecology Hospital affiliated with Tongji University between January 2015 and March 2023. The study focused on examining the ultrasound characteristics of different types of ovarian pregnancies and the accuracy of preoperative ultrasound diagnoses. RESULTS: The study included 68 patients with a median age of 30 (22-47) years. There were 43 cases (63.2%) of ruptured OEP and 25 (36.8%) of unruptured OEP. The unruptured cases were subclassified as embryonic sac type (n = 16) and heterogeneous mass type (n = 9). Preoperative ultrasound accurately diagnosed 19 cases (27.9%) of OEP, including 10 (62.50%) of the embryonic sac type, 4 (44.44%) of the heterogeneous mass type, and 5 (11.63%) of the ruptured type. Preoperative ultrasonography showed that embryonic sac type OEP was characterized by an intra-ovarian cystic structure with a distinctive hyperechoic ring and, in some cases (8 out of 16), the presence of embryonic buds and/or yolk sacs. Ruptured OEP was characterized by mixed masses in the pelvic cavity with minimal or significant free pelvic fluid, an unclear boundary between the mass and the ovary, and limited or no vascularity. CONCLUSIONS: Ultrasound may be used to determine the type of OEP preoperatively, with a higher diagnostic yield for the embryonic sac subtype. Preoperative ultrasonographic classification may enhance the preoperative diagnosis of OEP.
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The anthocyanin is a protective substance in various plants, and plays important roles in resisting to low-temperature. Here, we explored transcriptome analysis of pink flower (as CK) and the natural mutant red flower (as research objects) under low-temperature conditions, and aimed to reveal the potential functions of anthocyanins and anthocyanin-related regulatory factors in resistance to low-temperature. Our results showed that most of the differentially expressed genes (DEGs) encoding key enzymes in the late stage of anthocyanin metabolism in the mutant were significantly up-regulated. Meanwhile, several genes significantly differentially expressed in CK or mutant were obtained by classification and analysis of transcription factors (TFs), phytohormones and osmoregulators. Additionally, WGCNA was carried out to mine hub genes resistanted to low-temperature stress in flavonoid pathway. Finally, one UFGT family gene, three MYB and one bHLH were obtained as the future hub genes of this study. Combined with the above information, we concluded that the ability of the red flower mutant to grow and develop normally at low-temperatures was the result of a combination of flavonoids and cold resistance genes.
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Antocianinas , Transcriptoma , Antocianinas/genética , Temperatura , Flores/genética , Flores/metabolismo , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Pigmentação/genéticaRESUMO
Background: The objective of this study was to investigate the correlation between the 7-joint ultrasound score (US7) and disease activity in patients with rheumatoid arthritis (RA). Methods: Forty-four patients with active RA were assessed, and the correlation between US7 and disease activity indicators such as the disease activity score (DAS28), rheumatoid factor (RF), the erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) was analyzed. In addition, the proportions of US7 points accounted for by different joint regions and joint surfaces were analyzed. Results: RF, CRP, and ESR were significantly increased in the RA group compared with the control group (P < 0.05). In the RA group, DAS28 (r = 0.0.561, P < 0.01), RF (r = 0.635, P < 0.01), ESR (r = 0.585, P < 0.01), and CRP (r = 0.492, P < 0.01) were positively correlated with US7. In terms of contributions to US7, the most susceptible joint surface is the dorsal surface, and the most susceptible joint area is the dorsal wrist. Conclusion: US7 is positively correlated with disease activity indicators of RA, which can objectively reflect disease activity in RA patients and provide a reference for clinical diagnosis and efficacy evaluation.
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BACKGROUND: It is widely acknowledged that hypoxia and m6A/m5C/m1A RNA modifications promote the occurrence and development of tumors by regulating the tumor microenvironment. This study aimed to establish a novel liver cancer risk signature based on hypoxia and m6A/m5C/m1A modifications. METHODS: We collected data from The Cancer Genome Atlas (TCGA-LIHC), the National Omics Data Encyclopedia (NODE-HCC), the International Cancer Genome Consortium (ICGC), and the Gene Expression Omnibus (GEO) databases for our study (GSE59729, GSE41666). Using Cox regression and least absolute shrinkage and selection operator (LASSO) method, we developed a risk signature for liver cancer based on differentially expressed genes related to hypoxia and genes regulated by m6A/m5C/m1A modifications. We stratified patients into high- and low-risk groups and assessed differences between these groups in terms of gene mutations, copy number variations, pathway enrichment, stemness scores, immune infiltration, and predictive capabilities of the model for immunotherapy and chemotherapy efficacy. RESULTS: Our analysis revealed a significantly correlated between hypoxia and methylation as well as m6A/m5C/m1A RNA methylation. The three-gene prognosis signature (CEP55, DPH2, SMS) combining hypoxia and m6A/m5C/m1A regulated genes exhibited strong predictive performance in TCGA-LIHC, NODE-HCC, and ICGC-LIHC-JP cohorts. The low-risk group demonstrated a significantly better overall survival compared to the high-risk group (p < 0.0001 in TCGA, p = 0.0043 in NODE, p = 0.0015 in ICGC). The area under the curve (AUC) values for survival at 1, 2, and 3 years are all greater than 0.65 in the three cohorts. Univariate and Multivariate Cox regression analyses of the three datasets indicated that the signature could serve as an independent prognostic predictor (p < 0.001 in the three cohorts). The high-risk group exhibited more genome changes and higher homologous recombination deficiency scores and stemness scores. Analysis of immune infiltration and immune activation confirmed that the signature was associated with various immune microenvironment characteristics. Finally, patients in the high-risk group experienced a more favorable response to immunotherapy, and various common chemotherapy drugs. CONCLUSION: Our prognostic signature which integrates hypoxia and m6A/m5C/m1A-regulated genes, provides valuable insights for clinical prediction and treatment guidance for liver cancer patients.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/genética , Variações do Número de Cópias de DNA , Prognóstico , Hipóxia , Microambiente Tumoral/genética , ProteínasRESUMO
BACKGROUND: Uridine disphosphate (UDP) glycosyltransferases (UGTs) act upon a huge variety of highly diverse and complex substrates, such as phytohormones and specialized metabolites, to regulate plant growth, development, disease resistance, and environmental interactions. However, a comprehensive investigation of UGT genes in tobacco has not been conducted. RESULTS: In this study, we carried out a genome-wide analysis of family-1 UDP glycosyltransferases in Nicotiana tabacum. We predicted 276 NtUGT genes, which were classified into 18 major phylogenetic subgroups. The NtUGT genes were invariably distributed among all the 24 chromosomes with structural diversity in exon/intron structure, conserved motifs, and cis-acting elements of promoters. Three groups of proteins which involved in flavonoid biosynthesis, plant growth and development, transportation and modification were identified that interact with NtUGT proteins using the PPI analysis. Expression analysis of NtUGT genes in cold stress, drought stress and different flower color using both online RNA-Seq data and the realtime PCR analysis, suggested the distinct role of NtUGT genes in resistance of cold, drought and in flavonoid biosynthesis. The enzymatic activities of seven NtUGT proteins that potentially involved in flavonoid glycosylation were analyzed, and found that all seven exhibited activity on myricetin; six (NtUGT108, NtUGT123, NtUGT141, NtUGT155, NtUGT179, and NtUGT195) showed activity on cyanidin; and three (NtUGT108, NtUGT195, and NtUGT217) were active on the flavonol aglycones kaempferol and quercetin, which catalyzing the substrates (myricetin, cyanidin or flavonol) to form new products. We further investigated the enzymatic products and enzymatic properties of NtUGT108, NtUGT195, and NtUGT217, suggested their diverse enzymatic activity toward flavonol, and NtUGT217 showed the highest catalyzed efficient toward quercetin. Overexpression of NtUGT217 significantly increase the content levels of the quercetin-3-O-glucoside, quercetin-3-O-rutinoside and kaempferol-3-O-rutinoside in transgenic tobacco leaves. CONCLUSION: We identified 276 UGT genes in Nicotiana tabacum. Our study uncovered valuable information about the phylogenetic structure, distribution, genomic characters, expression patterns and enzymatic activity of NtUGT genes in tobacco. We further identified three NtUGT genes involved in flavonoid biosynthesis, and overexpressed NtUGT217 to validate its function in catalyze quercetin. The results provide key candidate NtUGT genes for future breeding of cold and drought resistance and for potential metabolic engineering of flavonoid compounds.
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Glicosiltransferases , Nicotiana , Quercetina , Flavonoides/metabolismo , Flavonóis , Glicosiltransferases/genética , Glicosiltransferases/metabolismo , Filogenia , Melhoramento Vegetal , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Quercetina/metabolismo , Estresse Fisiológico/genética , Nicotiana/genética , Nicotiana/metabolismo , Uridina/metabolismo , Difosfato de Uridina/metabolismoRESUMO
Exosomes are a class of nanoscale vesicles secreted by cells, which contain abundant information closely related to parental cells. The ultrasensitive detection of cancer-derived exosomes is highly significant for early non-invasive diagnosis of cancer. Here, an ultrasensitive nanomechanical sensor is reported, which uses a magnetic-driven microcantilever array to selectively detect oncogenic exosomes. A magnetic force, which can produce a far greater deflection of microcantilever than that produced by the intermolecular interaction force even with very low concentrations of target substances, is introduced. This method reduced the detection limit to less than 10 exosomes mL-1 . Direct detection of exosomes in the serum of patients with breast cancer and in healthy people showed a significant difference. This work improved the sensitivity by five orders of magnitude as compared to that of traditional nanomechanical sensing based on surface stress mode. This method can be applied parallelly for highly sensitive detection of other microorganisms (such as bacteria and viruses) by using different probe molecules, which can provide a supersensitive detection approach for cancer diagnosis, food safety, and SARS-CoV-2 infection.
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Técnicas Biossensoriais , Neoplasias da Mama , COVID-19 , Exossomos , Humanos , Feminino , Detecção Precoce de Câncer , COVID-19/diagnóstico , SARS-CoV-2 , Técnicas Biossensoriais/métodos , Neoplasias da Mama/diagnóstico , Teste para COVID-19RESUMO
Coral reefs are among the richest marine ecosystems on Earth, but there remains much diversity hidden within cavities of complex reef structures awaiting discovery. While the abundance of corals and other macroinvertebrates are known to influence the diversity of other reef-associated organisms, much remains unknown on the drivers of cryptobenthic diversity. A combination of standardized sampling with 12 units of the Autonomous Reef Monitoring Structure (ARMS) and high-throughput sequencing was utilized to uncover reef cryptobiome diversity across the equatorial reefs in Singapore. DNA barcoding and metabarcoding of mitochondrial cytochrome c oxidase subunit I, nuclear 18S and bacterial 16S rRNA genes revealed the taxonomic composition of the reef cryptobiome, comprising 15,356 microbial ASVs from over 50 bacterial phyla, and 971 MOTUs across 15 metazoan and 19 non-metazoan eukaryote phyla. Environmental factors across different sites were tested for relationships with ARMS diversity. Differences among reefs in diversity patterns of metazoans and other eukaryotes, but not microbial communities, were associated with biotic (coral cover) and abiotic (distance, temperature and sediment) environmental variables. In particular, ARMS deployed at reefs with higher coral cover had greater metazoan diversity and encrusting plate cover, with larger-sized non-coral invertebrates influencing spatial patterns among sites. Our study showed that DNA barcoding and metabarcoding of ARMS constitute a valuable tool for quantifying cryptobenthic diversity patterns and can provide critical information for the effective management of coral reef ecosystems.
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Antozoários , Microbiota , Animais , Recifes de Corais , Ecossistema , RNA Ribossômico 16S/genética , Antozoários/genética , DNA , BiodiversidadeRESUMO
BACKGROUND: Previous studies on cancer of unknown primary (CUP) mainly focus on treatment and prognosis in western populations and lacked clinical evaluation of different IHC markers, so this study aimed to evaluate characteristics of CUP and recommend a diagnostic strategy from a single center in China. METHODS AND RESULTS: Data of 625 patients with CUP were retrospectively collected and reviewed. The patients ranged in age from 20 to 91 years, with a female-to-male ratio of 1.3:1. The predominant histological type was poor or undifferentiated adenocarcinomas (308; 49.3%). The results of Canhelp-Origin molecular testing for the identification of the tissue of origin in 262 of 369 patients (71.0%) were considered predictable (similarity score > 45), with the most common predicted primary tumor site being the breast (57, 21.8%). Unpredictable molecular results correlated with more aggressive clinical parameters and poor survival. Thee positivity rates of several targeted antibodies (GATA3, GCDFP15, TTF1, Napsin A, and PAX8), based on the clinically predicted site, were lower than those reported for the corresponding primary tumors. Nonetheless, TRPS1 and INSM1 were reliable markers of predicted breast carcinoma (75.0%) and neuroendocrine tumors (83.3%), respectively. P16 expression, as well as HPV and EBER testing contributed significantly to the diagnosis of squamous cell carcinomas. Survival analysis revealed that older ages (> 57), ≥ 3 metastatic sites, non-squamous cell carcinomas, bone/liver/lung metastases, unpredictable molecular results, and palliative treatment correlated with poor overall survival. CONCLUSIONS: We recommend a CUP diagnostic strategy involving the use of targeted antibody panels as per histological findings that is potentially applicable in clinical practice. The markers TRPS1, INSM1, and P16 expression, as well as HPV and EBER testing are particularly valuable in this aspect. Molecular testing is also predictive of survival rates.
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Adenocarcinoma , Neoplasias Primárias Desconhecidas , Infecções por Papillomavirus , Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Neoplasias Primárias Desconhecidas/patologia , Estudos Retrospectivos , Biomarcadores Tumorais/metabolismo , Proteínas RepressorasRESUMO
BACKGROUND: Metastasis in a nonsentinel lymph node (non-SLN) is an unfavorable independent prognostic factor in cutaneous melanoma (CM). Recent data did suggest potential value of completion lymph node dissection (CLND) in CM patients with non-SLN metastasis. Prediction of non-SLN metastasis assists clinicians in deciding on adjuvant therapy without CLND. We analyzed risk factors and developed a prediction model for non-SLN status in acral melanoma (AM). METHODS: This retrospective study enrolled 656 cases of melanoma who underwent sentinel lymph node biopsy at Fudan University Shanghai Cancer Center from 2009 to 2017. We identified 81 SLN + AM patients who underwent CLND. Clinicopathologic data, including SLN tumor burden and non-SLN status were examined with Cox and Logistics regression models. RESULTS: Ulceration, Clark level, number of deposits in the SLN (NumDep) and maximum size of deposits (MaxSize) are independent risk factors associated with non-SLN metastases. We developed a scoring system that combines ulceration, the cutoff values of Clark level V, MaxSize of 2 mm, and NumDep of 5 to predict non-SLN metastasis with an efficiency of 85.2% and 100% positive predictive value in the high-rank group (scores of 17-24). CONCLUSIONS: A scoring system that included ulceration, Clark level, MaxSize, and NumDep is reliable and effective for predicting non-SLN metastasis in SLN-positive AM.
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Melanoma , Linfonodo Sentinela , Neoplasias Cutâneas , Humanos , Melanoma/patologia , Neoplasias Cutâneas/cirurgia , Neoplasias Cutâneas/patologia , Metástase Linfática/patologia , Linfonodo Sentinela/cirurgia , Linfonodo Sentinela/patologia , Estudos Retrospectivos , China , Biópsia de Linfonodo Sentinela , Linfonodos/cirurgia , Linfonodos/patologia , Excisão de Linfonodo , Prognóstico , Melanoma Maligno CutâneoRESUMO
Coral-associated bacteria play critical roles in the regulation of coral health and function. Environmental perturbations that alter the bacterial community structure can render the coral holobiont more susceptible and less resilient to disease. Understanding the natural variation of the coral microbiome across space and host species provides a baseline that can be used to distinguish shifts in community structure. Using a 16S rRNA gene metabarcoding approach, this study examines bacterial community structure across three scleractinian coral hosts. Our results show that corals of three regions-eastern and western Peninsular Malaysia and Singapore-host distinct bacterial communities; despite these differences, we were able to identify a core microbiome shared across all three species. This core microbiome was also present in samples previously collected in Thailand, suggesting that these core microbes play an important role in promoting and maintaining host health. For example, several have been identified as dimethylsulfoniopropionate (DMSP) metabolizers that have roles in sulfur cycling and the suppression of bacterial pathogens. Pachyseris speciosa has the most variable microbiome, followed by Porites lutea, with the composition of the Diploastrea heliopora microbiome the least variable throughout all locations. Microbial taxa associated with each region or site are likely shaped by local environmental conditions. Taken together, host identity is a major driver of differences in microbial community structure, while environmental heterogeneity shapes communities at finer scales.
Assuntos
Antozoários , Microbiota , Animais , Antozoários/microbiologia , Malásia , RNA Ribossômico 16S/genética , Bactérias/genética , Recifes de CoraisRESUMO
The majority of inflammatory myofibroblastic tumors (IMTs) in the gynecologic tract occur in the uterine corpus and harbor anaplastic lymphoma kinase ( ALK ) rearrangement. Herein, we report 1 uterine IMT case with a novel fusion involving ALK and 1 uterine IMT case with ROS1 rearrangement. The ages of the patients were 56 and 57 yr, respectively. The tumor size was 10.0 and 8.0 cm, respectively. Both patients had stage IB disease. Histologically, the 2 IMT cases had classic morphologic features and predominantly comprised bland spindle cells with hypercellular (fascicular/storiform) and hypocellular (myxoid rich) areas admixed with variably prominent lymphoplasmacytic infiltration. Immunohistochemically, the ALK -rearranged case was positive for ALK , and the ROS1 -rearranged case was positive for ROS1 . Both cases were diffusely positive for desmin. The tumor cells were variably positive for estrogen receptor (1/2 cases, 50.0%) and progesterone receptor (1/2 cases, 50.0%). Targeted RNA sequencing revealed one case each with either a novel CASC15-ALK or TFG-ROS 1 fusion. We identified a novel ALK fusion partner CASC15 in IMT and described the first uterine IMT with a TFG-ROS1 fusion. This study improves our understanding of molecular events in IMT.
Assuntos
Granuloma de Células Plasmáticas , Proteínas Tirosina Quinases , Humanos , Feminino , Quinase do Linfoma Anaplásico/genética , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Útero , ProteínasRESUMO
A structurally diverse set of chiral pyrazolo[3,4-b]pyridin-6-ones was efficiently prepared in excellent yields with excellent enantioselectivities via N-heterocyclic carbene-catalyzed oxidative [3 + 3] annulation of enals with pyrazol-5-amines. The reaction features mild reaction conditions, a broad substrate scope, and easy scale-up.