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1.
BMC Med ; 22(1): 55, 2024 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-38317152

RESUMO

BACKGROUND: Implementation of high-risk human papillomavirus (hrHPV) screening has greatly reduced the incidence and mortality of cervical cancer. However, a triage strategy that is effective, noninvasive, and independent from the subjective interpretation of pathologists is urgently required to decrease unnecessary colposcopy referrals in hrHPV-positive women. METHODS: A total of 3251 hrHPV-positive women aged 30-82 years (median = 41 years) from International Peace Maternity and Child Health Hospital were included in the training set (n = 2116) and the validation set (n = 1135) to establish Cervical cancer Methylation (CerMe) detection. The performance of CerMe as a triage for hrHPV-positive women was evaluated. RESULTS: CerMe detection efficiently distinguished cervical intraepithelial neoplasia grade 2 or worse (CIN2 +) from cervical intraepithelial neoplasia grade 1 or normal (CIN1 -) women with excellent sensitivity of 82.4% (95% CI = 72.6 ~ 89.8%) and specificity of 91.1% (95% CI = 89.2 ~ 92.7%). Importantly, CerMe showed improved specificity (92.1% vs. 74.9%) in other 12 hrHPV type-positive women as well as superior sensitivity (80.8% vs. 61.5%) and specificity (88.9% vs. 75.3%) in HPV16/18 type-positive women compared with cytology testing. CerMe performed well in the triage of hrHPV-positive women with ASC-US (sensitivity = 74.4%, specificity = 87.5%) or LSIL cytology (sensitivity = 84.4%, specificity = 83.9%). CONCLUSIONS: PCDHGB7 hypermethylation-based CerMe detection can be used as a triage strategy for hrHPV-positive women to reduce unnecessary over-referrals. TRIAL REGISTRATION: ChiCTR2100048972. Registered on 19 July 2021.


Assuntos
Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Feminino , Humanos , Metilação de DNA , Detecção Precoce de Câncer , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Papillomaviridae , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Estudos Prospectivos , Sensibilidade e Especificidade , Triagem , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/epidemiologia , Displasia do Colo do Útero/genética , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/genética , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais
2.
Small ; 20(27): e2311421, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38282177

RESUMO

To improve ion transport kinetics and electronic conductivity between the different phases in sodium/lithium-ion battery (LIB/SIB) anodes, heterointerface engineering is considered as a promising strategy due to the strong built-in electric field. However, the lattice mismatch and defects in the interphase structure can lead to large grain boundary resistance, reducing the ion transport kinetics and electronic conductivity. Herein, monometallic selenide Fe3Se4-Fe7Se8 semi-coherent heterointerface embedded in 3D connected Nitrogen-doped carbon yolk-shell matrix (Fe3Se4-Fe7Se8@NC) is obtained via an in situ phase transition process. Such semi-coherent heterointerface between Fe3Se4 and Fe7Se8 shows the matched interfacial lattice and strong built-in electric field, resulting in the low interface impedance and fast reaction kinetics. Moreover, the yolk-shell structure is designed to confine all monometallic selenide Fe3Se4-Fe7Se8 semi-coherent heterointerface nanoparticles, improving the structural stability and inhibiting the volume expansion effect. In particular, the 3D carbon bridge between multi-yolks shell structure improves the electronic conductivity and shortens the ion transport path. Therefore, the efficient reversible pseudocapacitance and electrochemical conversion reaction are enabled by the Fe3Se4-Fe7Se8@NC, leading to the high specific capacity of 439 mAh g-1 for SIB and 1010 mAh g-1 for LIB. This work provides a new strategy for constructing heterointerface of the anode for secondary batteries.

3.
J Transl Med ; 22(1): 608, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956589

RESUMO

BACKGROUND: Urothelial carcinoma (UC) is the second most common urological malignancy. Despite numerous molecular markers have been evaluated during the past decades, no urothelial markers for diagnosis and recurrence monitoring have shown consistent clinical utility. METHODS: The methylation level of tissue samples from public database and clinical collected were analyzed. Patients with UC and benign diseases of the urinary system (BUD) were enrolled to establish TAGMe (TAG of Methylation) assessment in a training cohort (n = 567) using restriction enzyme-based bisulfite-free qPCR. The performance of TAGMe assessment was further verified in the validation cohort (n = 198). Urine samples from 57 UC patients undergoing postoperative surveillance were collected monthly for six months after surgery to assess the TAGMe methylation. RESULTS: We identified TAGMe as a potentially novel Universal-Cancer-Only Methylation (UCOM) marker was hypermethylated in multi-type cancers and investigated its application in UC. Restriction enzyme-based bisulfite-free qPCR was used for detection, and the results of which were consistent with gold standard pyrosequencing. Importantly, hypermethylated TAGMe showed excellent sensitivity of 88.9% (95% CI: 81.4-94.1%) and specificity of 90.0% (95% CI: 81.9-95.3%) in efficiently distinguishing UC from BUD patients in urine and also performed well in different clinical scenarios of UC. Moreover, the abnormality of TAGMe as an indicator of recurrence might precede clinical recurrence by three months to one year, which provided an invaluable time window for timely and effective intervention to prevent UC upstaging. CONCLUSION: TAGMe assessment based on a novel single target in urine is effective and easy to perform in UC diagnosis and recurrence monitoring, which may reduce the burden of cystoscopy. Trial registration ChiCTR2100052507. Registered on 30 October 2021.


Assuntos
Biomarcadores Tumorais , Metilação de DNA , Recidiva Local de Neoplasia , Humanos , Metilação de DNA/genética , Masculino , Feminino , Biomarcadores Tumorais/urina , Biomarcadores Tumorais/genética , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/diagnóstico , Idoso , Urotélio/patologia , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/urina , Estudos de Coortes , Neoplasias Urológicas/genética , Neoplasias Urológicas/diagnóstico , Neoplasias Urológicas/urina , Reprodutibilidade dos Testes , Proteínas de Membrana , Proteínas de Neoplasias
4.
Hum Mol Genet ; 30(22): 2110-2122, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34196368

RESUMO

The well-established functions of UHRF1 converge to DNA biological processes, as exemplified by DNA methylation maintenance and DNA damage repair during cell cycles. However, the potential effect of UHRF1 on RNA metabolism is largely unexplored. Here, we revealed that UHRF1 serves as a novel alternative RNA splicing regulator. The protein interactome of UHRF1 identified various splicing factors. Among them, SF3B3 could interact with UHRF1 directly and participate in UHRF1-regulated alternative splicing events. Furthermore, we interrogated the RNA interactome of UHRF1, and surprisingly, we identified U snRNAs, the canonical spliceosome components, in the purified UHRF1 complex. Unexpectedly, we found H3R2 methylation status determines the binding preference of U snRNAs, especially U2 snRNAs. The involvement of U snRNAs in UHRF1-containing complex and their binding preference to specific chromatin configuration imply a finely orchestrated mechanism at play. Our results provided the resources and pinpointed the molecular basis of UHRF1-mediated alternative RNA splicing, which will help us better our understanding of the physiological and pathological roles of UHRF1 in disease development.


Assuntos
Processamento Alternativo , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Histonas/metabolismo , Fatores de Processamento de RNA/metabolismo , RNA Nuclear Pequeno/genética , Ubiquitina-Proteína Ligases/metabolismo , Proteínas Estimuladoras de Ligação a CCAAT/genética , Humanos , Metilação , Complexos Multiproteicos , Conformação de Ácido Nucleico , Ligação Proteica , RNA Nuclear Pequeno/metabolismo , Ubiquitina-Proteína Ligases/genética
5.
Nucleic Acids Res ; 49(15): 8556-8572, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34329471

RESUMO

Dysfunction of Tumour Suppressor Genes (TSGs) is a common feature in carcinogenesis. Epigenetic abnormalities including DNA hypermethylation or aberrant histone modifications in promoter regions have been described for interpreting TSG inactivation. However, in many instances, how TSGs are silenced in tumours are largely unknown. Given that miRNA with low expression in tumours is another recognized signature, we hypothesize that low expression of miRNA may reduce the activity of TSG related enhancers and further lead to inactivation of TSG during cancer development. Here, we reported that low expression of miRNA in cancer as a recognized signature leads to loss of function of TSGs in breast cancer. In 157 paired breast cancer and adjacent normal samples, tumour suppressor gene GPER1 and miR-339 are both downregulated in Luminal A/B and Triple Negative Breast Cancer subtypes. Mechanistic investigations revealed that miR-339 upregulates GPER1 expression in breast cancer cells by switching on the GPER1 enhancer, which can be blocked by enhancer deletion through the CRISPR/Cas9 system. Collectively, our findings reveal novel mechanistic insights into TSG dysfunction in cancer development, and provide evidence that reactivation of TSG by enhancer switching may be a promising alternative strategy for clinical breast cancer treatment.


Assuntos
Neoplasias da Mama/genética , Metilação de DNA/genética , MicroRNAs/genética , Receptores de Estrogênio/genética , Receptores Acoplados a Proteínas G/genética , Proteínas Supressoras de Tumor/genética , Neoplasias da Mama/patologia , Carcinogênese/genética , Elementos Facilitadores Genéticos/genética , Epigenômica , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Inativação Gênica , Humanos , Regiões Promotoras Genéticas/genética , RNA Neoplásico/genética , Sequências Reguladoras de Ácido Nucleico/genética
6.
Genome Res ; 29(2): 270-280, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30670627

RESUMO

Aberrant DNA methylation is a distinguishing feature of cancer. Yet, how methylation affects immune surveillance and tumor metastasis remains ambiguous. We introduce a novel method, Guide Positioning Sequencing (GPS), for precisely detecting whole-genome DNA methylation with cytosine coverage as high as 96% and unbiased coverage of GC-rich and repetitive regions. Systematic comparisons of GPS with whole-genome bisulfite sequencing (WGBS) found that methylation difference between gene body and promoter is an effective predictor of gene expression with a correlation coefficient of 0.67 (GPS) versus 0.33 (WGBS). Moreover, Methylation Boundary Shift (MBS) in promoters or enhancers is capable of modulating expression of genes associated with immunity and tumor metabolism. Furthermore, aberrant DNA methylation results in tissue-specific enhancer switching, which is responsible for altering cell identity during liver cancer development. Altogether, we demonstrate that GPS is a powerful tool with improved accuracy and efficiency over WGBS in simultaneously detecting genome-wide DNA methylation and genomic variation. Using GPS, we show that aberrant DNA methylation is associated with altering cell identity and immune surveillance networks, which may contribute to tumorigenesis and metastasis.


Assuntos
Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Análise de Sequência de DNA/métodos , Carcinogênese/genética , Linhagem Celular Tumoral , Elementos Facilitadores Genéticos , Genoma Humano , Humanos , Vigilância Imunológica/genética , Fígado/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Metástase Neoplásica , Regiões Promotoras Genéticas , Proteínas Ribossômicas/genética
7.
Hum Mol Genet ; 26(21): 4231-4243, 2017 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-29088426

RESUMO

Genetic and epigenetic information are faithfully duplicated and accurately transmitted to daughter cells to preserve cell identity during the cell cycle. However, how the chromatin-based epigenetic information beyond DNA sequence is stably transmitted along with the disruption and re-establishment of chromatin structure within a cell cycle remains largely unexplored. Through comprehensive analysis DNA methylation and nucleosome positioning patterns of HepG2 cells in G0/G1, early S, late S and G2/M phases, we found that DNA methylation may act as the prime element for epigenetic inheritance after replication, as DNA methylation was extremely stable in each cell cycle phase, while nucleosome occupancy showed notable phase dependent fluctuation. Nucleosome-Secured Regions (NSRs) occupied by polycomb-repressed chromatin played a role in repressing the irrelevant cell type-specific genes and were essential for preventing irrelevant transcription factors binding, while the well-defined Nucleosome-Depleted Regions (NDRs) marked the genes crucial for cell identity maintenance. Chromatin structure at NSRs and NDRs was well maintained throughout the cell cycle, which played crucial roles in steadily preserving the transcriptional identity of the cell to fulfill cell identity maintenance. Collectively, our results demonstrated that while chromatin architecture underwent dynamic changes during cell cycle progression, DNA methylation together with NSRs and NDRs were stable epigenetic elements that were required for faithful transmission to the daughter cell to accurately maintain cell identity during the cell cycle.


Assuntos
Montagem e Desmontagem da Cromatina/fisiologia , Cromatina/fisiologia , Epigênese Genética/genética , Ciclo Celular/genética , Ciclo Celular/fisiologia , Divisão Celular , Cromatina/metabolismo , Montagem e Desmontagem da Cromatina/genética , Metilação de DNA/fisiologia , Epigenômica , Células Hep G2/metabolismo , Histonas/metabolismo , Humanos , Nucleossomos/metabolismo , Nucleossomos/efeitos da radiação , Proteínas do Grupo Polycomb/genética , Fatores de Transcrição/genética
8.
Small ; 15(30): e1900001, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31074926

RESUMO

The large-scale commercial application of lithium-oxygen batteries (LOBs) is overwhelmed by the sluggish kinetics of oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) associated with insoluble and insulated Li2 O2 . Herein, an elaborate design on a highly catalytic LOBs cathode constructed by N-doped carbon nanotubes (CNT) with in situ encapsulated Co2 P and Ru nanoparticles is reported. The homogeneously dispersed Co2 P and Ru catalysts can effectively modulate the formation and decomposition behavior of Li2 O2 during discharge/charge processes, ameliorating the electronically insulating property of Li2 O2 and constructing a homogenous low-impedance Li2 O2 /catalyst interface. Compared with Co/CNT and Ru/CNT electrodes, the Co2 P/Ru/CNT electrode delivers much higher oxygen reduction triggering onset potential and higher ORR and OER peak current and integral areas, showing greatly improved ORR/OER kinetics due to the synergistic effects of Co2 P and Ru. Li-O2 cells based on the Ru/Co2 P/CNT electrode demonstrate improved ORR/OER overpotential of 0.75 V, excellent rate capability of 12 800 mAh g-1 at 1 A g-1 , and superior cycle stability for more than 185 cycles under a restricted capacity of 1000 mAh g-1 at 100 mA g-1 . This work paves an exciting avenue for the design and construction of bifunctional catalytic cathodes by coupling metal phosphides with other active components in LOBs.

9.
J Cell Sci ; 129(5): 1059-71, 2016 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-26769901

RESUMO

Ten-eleven translocation (Tet) proteins are key players involved in the dynamic regulation of cytosine methylation and demethylation. Inactivating mutations of Tet2 are frequently found in human malignancies, highlighting the essential role of Tet2 in cellular transformation. However, the factors that control Tet enzymatic activity remain largely unknown. Here, we found that methyl-CpG-binding domain protein 3 (MBD3) and its homolog MBD3-like 2 (MBD3L2) can specifically modulate the enzymatic activity of Tet2 protein, but not Tet1 and Tet3 proteins, in converting 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). Moreover, MBD3L2 is more effective than MBD3 in promoting Tet2 enzymatic activity through strengthening the binding affinity between Tet2 and the methylated DNA target. Further analysis revealed pronounced decreases in 5mC levels at MBD3L2 and Tet2 co-occupied genomic regions, most of which are promoter elements associated with either cancer-related genes or genes involved in the regulation of cellular metabolic processes. Our data add new insights into the regulation of Tet2 activity by MBD3 and MBD3L2, and into how that affects Tet2-mediated modulation of its target genes in cancer development. Thus, they have important applications in understanding how dysregulation of Tet2 might contribute to human malignancy.


Assuntos
5-Metilcitosina/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Repressoras/fisiologia , Cromatina/metabolismo , Ilhas de CpG , Metilação de DNA , Dioxigenases , Células HEK293 , Humanos , Oxirredução , Ligação Proteica
10.
Cell Physiol Biochem ; 47(4): 1556-1564, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29940591

RESUMO

BACKGROUND/AIMS: Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at an advanced stage, resulting in extremely poor 5-year survival. Late diagnosis of PDAC is mainly due to lack of a reliable method of early detection. Carbohydrate antigen (CA) 19-9 is often used as a tumor biomarker in PDAC; however, the test lacks sensitivity and specificity. Therefore, new sensitive and minimally invasive diagnostic tools are required to detect pancreatic cancer. METHODS: Here, we investigated circulating tumor DNA (ctDNA) which contained KRAS-mutated as a potential diagnostic tool for PDAC patients who underwent irreversible electroporation (IRE). We used droplet digital polymerase chain reaction (ddPCR) to detect the expression of KRAS-mutated genes in plasma samples of 65 PDAC patients who underwent IRE. RESULTS: In these 65 cases, ctDNA was detected in 20 (29.2%) samples. The median overall survival (OS) was 11.4 months with ctDNA+ patients and 14.3 months for ctDNA- patients. ctDNA+ patients had a obviously poorer prognosis associated to overall survival (P < 0.001). CONCLUSION: Our results suggested that the existence of ctDNA was a predictor of survival for PDAC patients. Therefore, ctDNA may be a new sensitive biomarker for monitoring treatment outcome in PDAC.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Ductal Pancreático , DNA Tumoral Circulante/sangue , Eletroquimioterapia , Neoplasias Pancreáticas , Adulto , Idoso , Carcinoma Ductal Pancreático/sangue , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/mortalidade , Reação em Cadeia da Polimerase , Taxa de Sobrevida
11.
Small ; 14(16): e1704517, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29575525

RESUMO

Combining the advantage of metal, metal sulfide, and carbon, mesoporous hollow core-shell Sb/ZnS@C hybrid heterostructures composed of Sb/ZnS inner core and carbon outer shell are rationally designed based on a robust template of ZnS nanosphere, as anodes for high-performance sodium-ion batteries (SIBs). A partial cation exchange reaction based on the solubility difference between Sb2 S3 and ZnS can transform mesoporous ZnS to Sb2 S3 /ZnS heterostructure. To get a stable structure, a thin contiguous resorcinol-formaldehyde (RF) layer is introduced on the surface of Sb2 S3 /ZnS heterostructure. The effectively protective carbon layer from RF can be designed as the reducing agent to convert Sb2 S3 to metallic Sb to obtain core-shell Sb/ZnS@C hybrid heterostructures. Simultaneously, the carbon outer shell is beneficial to the charge transfer kinetics, and can maintain the structure stability during the repeated sodiation/desodiation process. Owing to its unique stable architecture and synergistic effects between the components, the core-shell porous Sb/ZnS@C hybrid heterostructure SIB anode shows a high reversible capacity, good rate capability, and excellent cycling stability by turning the optimized voltage range. This novel strategy to prepare carbon-layer-protected metal/metal sulfide core-shell heterostructure can be further extended to design other novel nanostructured systems for high-performance energy storage devices.

13.
RNA Biol ; 14(10): 1326-1334, 2017 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-26853707

RESUMO

MicroRNAs (miRNAs) are small non-coding RNAs that function as negative gene expression regulators. Emerging evidence shows that, except for function in the cytoplasm, miRNAs are also present in the nucleus. However, the functional significance of nuclear miRNAs remains largely undetermined. By screening miRNA database, we have identified a subset of miRNA that functions as enhancer regulators. Here, we found a set of miRNAs show gene-activation function. We focused on miR-24-1 and found that this miRNA unconventionally activates gene transcription by targeting enhancers. Consistently, the activation was completely abolished when the enhancer sequence was deleted by TALEN. Furthermore, we found that miR-24-1 activates enhancer RNA (eRNA) expression, alters histone modification, and increases the enrichment of p300 and RNA Pol II at the enhancer locus. Our results demonstrate a novel mechanism of miRNA as an enhancer trigger.


Assuntos
Cromatina/metabolismo , Elementos Facilitadores Genéticos , MicroRNAs/genética , Ativação Transcricional , Cromatina/química , Bases de Dados Genéticas , Proteína p300 Associada a E1A/metabolismo , Epigênese Genética , Perfilação da Expressão Gênica/métodos , Células HEK293 , Histonas/metabolismo , Humanos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , RNA Polimerase II/metabolismo
14.
ACS Appl Mater Interfaces ; 16(2): 2438-2448, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38180810

RESUMO

The large grain boundary resistance between different components of the anode electrode easily leads to the low ion transport efficiency and poor electrochemical performance of lithium-/sodium-ion batteries (LIBs/SIBs). To address the issue, a Janus heterointerface with a Mott-Schottky structure is proposed to optimize the interface atomic structure, weaken interatomic resistance, and improve ion transport kinetics. Herein, Janus Co/Co2P@carbon-nanotubes@core-shell (Janus Co/Co2P@CNT-CS) refined urchin-like architecture derived from metal-organic frameworks is reported via a coating-phosphating process, where the Janus Co/Co2P heterointerface nanoparticles are confined in carbon nanotubes and a core-shell polyhedron. Such a Janus Co/Co2P heterointerface shows the strong built-in electric field, facilitating the controllable ion transport channels and the high ion transport efficiency. The Janus Co/Co2P@CNT-CS refined urchin-like architecture composed of a core-shell structure and the grafting carbon nanotubes enhances the structure stability and electronic conductivity. Benefiting from the spaced-confined Janus heterointerface engineering and synergistic effects between the core-shell structure and the grafting carbon nanotubes, the Janus Co/Co2P@CNT-CS refined urchin-like architecture demonstrates the fast ion transport rate and excellent pseudocapacitance performance for LIBs/SIBs. In this case, the Janus Co/Co2P@CNT-CS refined urchin-like architecture shows high specific capacities of 709 mA h g-1 (200 cycles) and 203 mA h g-1 (300 cycles) at a current density of 500 mA g-1 for LIBs/SIBs, respectively.

15.
JCI Insight ; 9(7)2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38587071

RESUMO

BACKGROUNDDifferentiating malignant from nonmalignant body fluids remains a clinical challenge because of the unsatisfying performance of conventional cytology. We aimed to improve the sensitivity and ubiquity of cancer cell detection by assaying universal cancer-only methylation (UCOM) markers in supernatant cell-free DNA (cfDNA).METHODSAn observational prospective cohort including 1,321 nonmalignant and malignant body fluids of multiple cancers was used to develop and validate a cfDNA UCOM methylation diagnostic assay. All samples were divided into 2 portions for cytology and supernatant cfDNA methylation analysis.RESULTSThe significant hypermethylation of a potentially novel UCOM marker, TAGMe, together with the formerly reported PCDHGB7, was identified in the cfDNA of malignant body fluid samples. The combined model, cell-free cancer-universal methylation (CUE), was developed and validated in a prospective multicancer cohort with markedly elevated sensitivity and specificity, and was further verified in a set containing additional types of malignant body fluids and metastases. In addition, it remained hypersensitive in detecting cancer cells in cytologically negative malignant samples.CONCLUSIONcfDNA methylation markers are robust in detecting tumor cells and are applicable to diverse body fluids and tumor types, providing a feasible complement to current cytology-based diagnostic analyses.TRIAL REGISTRATIONThis study was registered at Chictr.org.cn (ChiCTR2200060532).FUNDINGNational Natural Science Foundation of China (32270645, 31872814, 32000505, 82170088), the National Key R&D Program of Ningxia Hui Autonomous region (2022BEG01003), Shanghai Municipal Key Clinical Specialty (shslczdzk02201), Science and Technology Commission of Shanghai Municipality (20DZ2261200, 20DZ2254400), and Major Special Projects of Basic Research of Shanghai Science and Technology Commission (18JC1411101).


Assuntos
Líquidos Corporais , Ácidos Nucleicos Livres , Neoplasias , Humanos , Ácidos Nucleicos Livres/genética , Estudos Prospectivos , China , Neoplasias/diagnóstico , Neoplasias/genética , Metilação de DNA
16.
Nat Commun ; 14(1): 3302, 2023 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-37280214

RESUMO

Growth constitutes a powerful method to post-modulate materials' structures and functions without compromising their mechanical performance for sustainable use, but the process is irreversible. To address this issue, we here report a growing-degrowing strategy that enables thermosetting materials to either absorb or release components for continuously changing their sizes, shapes, compositions, and a set of properties simultaneously. The strategy is based on the monomer-polymer equilibrium of networks in which supplying or removing small polymerizable components would drive the networks toward expansion or contraction. Using acid-catalyzed equilibration of siloxane as an example, we demonstrate that the size and mechanical properties of the resulting silicone materials can be significantly or finely tuned in both directions of growth and decomposition. The equilibration can be turned off to yield stable products or reactivated again. During the degrowing-growing circle, material structures are selectively varied either uniformly or heterogeneously, by the availability of fillers. Our strategy endows the materials with many appealing capabilities including environment adaptivity, self-healing, and switchability of surface morphologies, shapes, and optical properties. Since monomer-polymer equilibration exists in many polymers, we envision the expansion of the presented strategy to various systems for many applications.

17.
ACS Appl Mater Interfaces ; 14(3): 4571-4578, 2022 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-35020361

RESUMO

Polymer coatings with comprehensive properties including passive radiative cooling, anti-fouling, and self-healing constitute a promising energy-saving strategy but have not been well documented yet. Herein, we reported a class of novel multifunctional supramolecular polysiloxane composite coatings showing the combination of these features. The coatings have a hybrid structure with a slippery liquid-infused porous surface and a gradient polymer-Al2O3 composite matrix constructed by reversible hydrogen bonding. The gradient matrix consists of a polymer-rich top and a particle-rich bottom favoring coating attachment on rigid substrates. Such a complex structure can be obtained by simply casting the suspending solutions of the polydimethylsiloxane (PDMS)-urea copolymer and Al2O3 on substrates followed by swelling silicone oil. Obtained coatings display good passive daytime radiative cooling (a temperature drop of ∼2 °C), self-healing ability, and anti-fouling properties. Since the comprehensive performances and the facile fabrication, the coatings should have application potential for various thermal management purposes.

18.
Nat Commun ; 13(1): 7823, 2022 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-36535934

RESUMO

Many organisms produce stunning optical displays based on structural color instead of pigmentation. This structural or photonic color is achieved through the interaction of light with intricate micro-/nano-structures, which are "grown" from strong, sustainable biological materials such as chitin, keratin, and cellulose. In contrast, current synthetic structural colored materials are usually brittle, inert, and produced via energy-intensive processes, posing significant challenges to their practical uses. Inspired by the brilliantly colored peacock feathers which selectively grow keratin-based photonic structures with different photonic bandgaps, we develop a self-growing photonic composite system in which the photonic bandgaps and hence the coloration can be easily tuned. This is achieved via the selective growth of the polymer matrix with polymerizable compounds as feeding materials in a silica nanosphere-polymer composite system, thus effectively modulating the photonic bandgaps without compromising nanostructural order. Such strategy not only allows the material system to continuously vary its colors and patterns in an on-demand manner, but also endows it with many appealing properties, including flexibility, toughness, self-healing ability, and reshaping capability. As this innovative self-growing method is simple, inexpensive, versatile, and scalable, we foresee its significant potential in meeting many emerging requirements for various applications of structural color materials.


Assuntos
Nanoestruturas , Polímeros , Animais , Polímeros/química , Pigmentação , Fótons , Celulose
19.
Front Mol Biosci ; 8: 774215, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35059435

RESUMO

Endometrial cancer (EC) is one of the most common gynecologic cancers in developed countries. Presently, it is imperative to develop a reliable, noninvasive, or minimally invasive detection method for EC. We explored the possibility of using DNA methylation marker from endometrial brush samples (with a "Tao brush") and cervical scrapes (with a "Pap brush") for early detection of EC. We analyzed the methylation data of EC and normal endometrial tissues from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data sets. An optimized methylation-sensitive restriction enzyme combined with real-time fluorescent quantitative PCR (MSRE-qPCR) was used for methylation detection. Included in the training set were 143 endometrial tissues, 103 Tao, and 109 Pap brush samples. The validation set included 110 Tao and 112 Pap brush samples. PCDHGB7 was significantly hypermethylated in EC compared with normal endometrial tissues in the TCGA and GEO data sets (AUC >0.95), which was verified in clinical samples. In the Pap brush samples, the AUC was 0.86 with 80.65% sensitivity and 82.81% specificity, whereas the Tao brush samples exhibited higher specificity (95.31%). The combination of Tao and Pap brush samples significantly increased the sensitivity to 90.32%. In the validation set, the final model yielded a sensitivity of 98.61%, specificity of 60.53%, positive predictive value of 82.56%, and negative predictive value of 95.83%. These results demonstrate the potential application of the novel methylation marker, hypermethylated PCDHGB7, in cervical scrapings and endometrial brush, which provides a viable, noninvasive, or minimally invasive method for early endometrial cancer detection across different clinical features and histologies to supplement current hysteroscopy diagnosis.

20.
ACS Appl Mater Interfaces ; 12(35): 39657-39664, 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32805856

RESUMO

Droplet-embedded structures are useful in functionalizing polymer composites but difficult to prepare. Herein, we report a facile self-born method for creating droplets in supramolecular gels to mediate the material's functions. This method is based on the amplification of the defects of polymer matrices generated in curing by swelling-driving reconfiguration of supramolecular polymer networks. The system of poly(urea-co-polydimethylsiloxane) that can cross-link via hydrogen-bond interaction is used to demonstrate our concept. The elastomer matrices are prepared via a casting method and exhibit a heterogeneous structure with both strong- and weak-cross-linking domains. When these materials are swelled in solvents, solvent molecules concentrate in the weak-cross-linking domains to nucleate. With the reconfiguration of the matrices, the nuclei grow into pure droplets, leading to the formation of droplet-embedded structures. This method is applicable to different material systems. We also show that obtained coatings with such droplet-embedded structures exhibit various interesting properties including self-replenishment of the surface liquid, mechanoresponsiveness, and self-healing ability. Moreover, after the droplets are consumed, this method can be used to regenerate the droplet-embedded structure for refunctionalizing the materials. Therefore, we envision its applications in preparation of many useful polymer composites.

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