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1.
Nature ; 627(8004): 586-593, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38355797

RESUMO

Over half of hepatocellular carcinoma (HCC) cases diagnosed worldwide are in China1-3. However, whole-genome analysis of hepatitis B virus (HBV)-associated HCC in Chinese individuals is limited4-8, with current analyses of HCC mainly from non-HBV-enriched populations9,10. Here we initiated the Chinese Liver Cancer Atlas (CLCA) project and performed deep whole-genome sequencing (average depth, 120×) of 494 HCC tumours. We identified 6 coding and 28 non-coding previously undescribed driver candidates. Five previously undescribed mutational signatures were found, including aristolochic-acid-associated indel and doublet base signatures, and a single-base-substitution signature that we termed SBS_H8. Pentanucleotide context analysis and experimental validation confirmed that SBS_H8 was distinct to the aristolochic-acid-associated SBS22. Notably, HBV integrations could take the form of extrachromosomal circular DNA, resulting in elevated copy numbers and gene expression. Our high-depth data also enabled us to characterize subclonal clustered alterations, including chromothripsis, chromoplexy and kataegis, suggesting that these catastrophic events could also occur in late stages of hepatocarcinogenesis. Pathway analysis of all classes of alterations further linked non-coding mutations to dysregulation of liver metabolism. Finally, we performed in vitro and in vivo assays to show that fibrinogen alpha chain (FGA), determined as both a candidate coding and non-coding driver, regulates HCC progression and metastasis. Our CLCA study depicts a detailed genomic landscape and evolutionary history of HCC in Chinese individuals, providing important clinical implications.


Assuntos
Carcinoma Hepatocelular , Genoma Humano , Sequenciamento de Nucleotídeos em Larga Escala , Neoplasias Hepáticas , Mutação , Sequenciamento Completo do Genoma , Humanos , Ácidos Aristolóquicos/metabolismo , Carcinogênese , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/virologia , China , Cromotripsia , Progressão da Doença , DNA Circular/genética , População do Leste Asiático/genética , Evolução Molecular , Genoma Humano/genética , Vírus da Hepatite B/genética , Mutação INDEL/genética , Fígado/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virologia , Mutação/genética , Metástase Neoplásica/genética , Fases de Leitura Aberta/genética , Reprodutibilidade dos Testes
2.
J Biol Chem ; 299(5): 104677, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37028765

RESUMO

The N6-methyladenosine (m6A) modification possesses new and essential roles in tumor initiation and progression by regulating mRNA biology. However, the role of aberrant m6A regulation in nasopharyngeal carcinoma (NPC) remains unclear. Here, through comprehensive analyses of NPC cohorts from the GEO database and our internal cohort, we identified that VIRMA, an m6A writer, is significantly upregulated in NPC and plays an essential role in tumorigenesis and metastasis of NPC, both in vitro and in vivo. High VIRMA expression served as a prognostic biomarker and was associated with poor outcomes in patients with NPC. Mechanistically, VIRMA mediated the m6A methylation of E2F7 3'-UTR, then IGF2BP2 bound, and maintained the stability of E2F7 mRNA. An integrative high-throughput sequencing approach revealed that E2F7 drives a unique transcriptome distinct from the classical E2F family in NPC, which functioned as an oncogenic transcriptional activator. E2F7 cooperated with CBFB-recruited RUNX1 in a non-canonical manner to transactivate ITGA2, ITGA5, and NTRK1, strengthening Akt signaling-induced tumor-promoting effect.


Assuntos
Carcinogênese , Fator de Transcrição E2F7 , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Proteínas de Ligação a RNA , Humanos , Carcinogênese/genética , Transformação Celular Neoplásica , Fator de Transcrição E2F7/genética , Fator de Transcrição E2F7/metabolismo , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , RNA Mensageiro/genética , Proteínas de Ligação a RNA/metabolismo , Regulação para Cima
3.
J Biol Chem ; 299(7): 104873, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37257820

RESUMO

Dysregulation of long noncoding RNAs (lncRNAs) contributes to tumorigenesis by modulating specific cancer-related pathways, but the roles of N6-methyladenosine (m6A)-enriched lncRNAs and underlying mechanisms remain elusive in nasopharyngeal carcinoma (NPC). Here, we reanalyzed the previous genome-wide analysis of lncRNA profiles in 18 pairs of NPC and normal tissues as well as in ten paired samples from NPC with or without post-treatment metastases. We discerned that an oncogenic m6A-enriched lncRNA, LINC00839, which was substantially upregulated in NPC and correlated with poor clinical prognosis, promoted NPC growth and metastasis both in vitro and in vivo. Mechanistically, by using RNA pull-down assay combined with mass spectrometry, we found that LINC00839 interacted directly with the transcription factor, TATA-box binding protein associated factor (TAF15). Besides, chromatin immunoprecipitation and dual-luciferase report assays demonstrated that LINC00839 coordinated the recruitment of TAF15 to the promoter region of amine oxidase copper-containing 1 (AOC1), which encodes a secreted glycoprotein playing vital roles in various cancers, thereby activating AOC1 transcription in trans. In this study, potential effects of AOC1 in NPC progression were first proposed. Moreover, ectopic expression of AOC1 partially rescued the inhibitory effect of downregulation of LINC00839 in NPC. Furthermore, we showed that silencing vir-like m6A methyltransferase-associated (VIRMA) and insulin-like growth factor 2 mRNA-binding proteins 1 (IGF2BP1) attenuated the expression level and RNA stability of LINC00839 in an m6A-dependent manner. Taken together, our study unveils a novel oncogenic VIRMA/IGF2BP1-LINC00839-TAF15-AOC1 axis and highlights the significance and prognostic value of LINC00839 expression in NPC carcinogenesis.


Assuntos
Neoplasias Nasofaríngeas , RNA Longo não Codificante , Fatores Associados à Proteína de Ligação a TATA , Humanos , Aminas , Carcinogênese/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Oxirredutases/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fatores Associados à Proteína de Ligação a TATA/genética , Fatores Associados à Proteína de Ligação a TATA/metabolismo
4.
Gastroenterology ; 164(3): 407-423.e17, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36574521

RESUMO

BACKGROUND & AIMS: Lack of thorough knowledge about the complicated immune microenvironment (IM) within a variety of liver metastases (LMs) leads to inappropriate treatment and unsatisfactory prognosis. We aimed to characterize IM subtypes and investigate potential mechanisms in LMs. METHODS: Mass cytometry was applied to characterize immune landscape of a primary liver cancers and liver metastases cohort. Transcriptomic and whole-exome sequencing were used to explore potential mechanisms across distinct IM subtypes. Single-cell transcriptomic sequencing, multiplex fluorescent immunohistochemistry, cell culture, mouse model, Western blot, quantitative polymerase chain reaction, and immunohistochemistry were used for validation. RESULTS: Five IM subtypes were revealed in 100 LMs and 50 primary liver cancers. Patients featured terminally exhausted (IM1) or rare T-cell-inflamed (IM2 and IM3) immune characteristics showed worse outcome. Increased intratumor heterogeneity, enriched somatic TP53, KRAS, APC, and PIK3CA mutations and hyperactivated hypoxia signaling accounted for the formation of vicious subtypes. SLC2A1 promoted immune suppression and desert via increasing proportion of Spp1+ macrophages and their inhibitory interactions with T cells in liver metastatic lesions. Furthermore, SLC2A1 promoted immune escape and LM through inducing regulatory T cells, including regulatory T cells and LAG3+CD4+ T cells in primary colorectal cancer. CONCLUSIONS: The study provided integrated multi-omics landscape of LM, uncovering potential mechanisms for vicious IM subtypes and confirming the roles of SLC2A1 in regulating tumor microenvironment remodeling in both primary tumor and LM lesions.


Assuntos
Neoplasias Hepáticas , Multiômica , Animais , Camundongos , Mutação , Neoplasias Hepáticas/patologia , Sequenciamento do Exoma , Microambiente Tumoral
5.
Small ; : e2307610, 2024 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-38342695

RESUMO

Borophene, a 2D material exhibiting unique crystallographic phases like the anisotropic atomic lattices of ß12 and X3 phases, has attracted considerable attention due to its intriguing Dirac nature and metallic attributes. Despite surpassing graphene in electronic mobility, borophene's potential in energy storage and catalysis remains untapped due to its inherent electrochemical and catalytic limitations. Elemental doping emerges as a promising strategy to introduce charge carriers, enabling localized electrochemical and catalytic functionalities. However, effective doping of borophene has been a complex and underexplored challenge. Here, an innovative, one-pot microwave-assisted doping method, tailored for the ß12 phase of borophene is introduced. By subjecting dispersed ß12 borophene in dimethylformamide to controlled microwave exposure with sulfur powder and FeCl3 as doping precursors, S- and Fe doping in borophene can be controlled. Employing advanced techniques including high-resolution transmission electron microscopy, Raman spectroscopy, and X-ray photoelectron spectroscopy, confirm successful sulfur and iron dopant incorporation onto ß12 borophene is confirmed, achieving doping levels of up to 11 % and 13 %, respectively. Remarkably, S- and Fe-doped borophene exhibit exceptional supercapacitive behavior, with specific capacitances of 202 and 120 F g-1 , respectively, at a moderate current density of 0.25 A g-1 .

6.
Small ; : e2404337, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958089

RESUMO

Monoelemental atomic sheets (Xenes) and other 2D materials offer record electronic mobility, high thermal conductivity, excellent Young's moduli, optical transparency, and flexural capability, revolutionizing ultrasensitive devices and enhancing performance. The ideal synthesis of these quantum materials should be facile, fast, scalable, reproducible, and green. Microwave expansion followed by cryoquenching (MECQ) leverages thermal stress in graphite to produce high-purity graphene within minutes. MECQ synthesis of graphene is reported at 640 and 800 W for 10 min, followed by liquid nitrogen quenching for 5 and 90 min of sonication. Microscopic and spectroscopic analyses confirmed the chemical identity and phase purity of monolayers and few-layered graphene sheets (200-12 µm). Higher microwave power yields thinner layers with enhanced purity. Molecular dynamics simulations and DFT calculations support the exfoliation under these conditions. Electrostatic droplet switching is demonstrated using MECQ-synthesized graphene, observing electrorolling of a mercury droplet on a BN/graphene interface at voltages above 20 V. This technique can inspire the synthesis of other 2D materials with high purity and enable new applications.

7.
Sci Technol Adv Mater ; 25(1): 2357062, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38835629

RESUMO

Affordable and environmentally friendly electrochemically active raw energy storage materials are in high demand to switch to mass-scale renewable energy. One particularly promising avenue is the feasibility of utilizing food waste-derived nanoporous carbon. This material holds significance due to its widespread availability, affordability, ease of processing, and, notably, its cost-free nature. Over the years, various strategies have been developed to convert different food wastes into nanoporous carbon materials with enhanced electrochemical properties. The electrochemical performance of these materials is influenced by both intrinsic factors, such as the composition of elements derived from the original food sources and recipes, and extrinsic factors, including the conditions during pyrolysis and activation. While current efforts are dedicated to optimizing process parameters to achieve superior performance in electrochemical energy storage devices, it is timely to take stock of the current state of research in this emerging field. This review provides a comprehensive overview of recent developments in the fabrication and surface characterisation of porous carbons from different food wastes. A special focus is given on the applications of these food waste derived porous carbons for energy storage applications including batteries and supercapacitors.


This review compiles very recent literature on the synthesis of porous carbon from food waste biomass and their efficient utilisation as electrode material for energy storage applications in supercapacitor devices.

8.
Angew Chem Int Ed Engl ; : e202400494, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38598042

RESUMO

The photoredox electron donor-acceptor (EDA) complex-mediated radical coupling reaction has gained prominence in the field of organic synthesis, finding widespread application in two-component coupling reactions. However, EDA complex-promoted multi-component reactions are not well developed with only a limited number of examples have been reported. Herein, we report a photoinduced and EDA complex-promoted highly chemoselective three-component radical arylalkylation of [1.1.1]propellane, which allows the direct functionalization of C(sp3)-H with bicyclo[1.1.1]pentanes (BCP)-aryl groups under mild conditions. A variety of unnatural α-amino acids, featuring structurally diversified 1,3-disubstituted BCP moieties, were synthesized in a single-step process. Notably, leveraging the high tension release of [1.1.1]propellane, the highly unstable transient aryl radical undergoes rapid conversion into a relatively stable tertiary alkyl transient radical, and consequently, the competing side-reaction of two-component coupling was entirely suppressed. The strategic use of this transient radical conversion approach would be useful for the design of diverse EDA complex-mediated multi-component reactions. It is noteworthy that the highly chemoselective late-stage incorporation of the 1,3-disubstituted BCP pharmacophores into peptides was achieved both in liquid-phase and solid-phase reactions. This advancement is anticipated to have significant application potential in the future development of peptide drugs.

9.
Small ; 19(17): e2207181, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36693792

RESUMO

Carbon-based quantum dots (QDs) have emerged as a fascinating class of advanced materials with a unique combination of optoelectronic, biocompatible, and catalytic characteristics, apt for a plethora of applications ranging from electronic to photoelectrochemical devices. Recent research works have established carbon-based QDs for those frontline applications through improvements in materials design, processing, and device stability. This review broadly presents the recent progress in the synthesis of carbon-based QDs, including carbon QDs, graphene QDs, graphitic carbon nitride QDs and their heterostructures, as well as their salient applications. The synthesis methods of carbon-based QDs are first introduced, followed by an extensive discussion of the dependence of the device performance on the intrinsic properties and nanostructures of carbon-based QDs, aiming to present the general strategies for device designing with optimal performance. Furthermore, diverse applications of carbon-based QDs are presented, with an emphasis on the relationship between band alignment, charge transfer, and performance improvement. Among the applications discussed in this review, much focus is given to photo and electrocatalytic, energy storage and conversion, and bioapplications, which pose a grand challenge for rational materials and device designs. Finally, a summary is presented, and existing challenges and future directions are elaborated.

10.
Opt Lett ; 48(5): 1100-1103, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36857223

RESUMO

We demonstrate a chip-based octave-spanning soliton microcomb in a whispering gallery mode microresonator platform. By fabricating a silica microdisk resonator and optimizing its dispersion with dry etching, we achieve an octave-spanning single-soliton microcomb with a repetition rate of ∼670 GHz at an optical pump power of 162.6 mW. Also, two dispersive waves at the end of the spectrum are observed to extend the comb spectral range and improve the comb power.

11.
Pediatr Dermatol ; 40(5): 841-850, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37529963

RESUMO

BACKGROUND: Dupilumab is the first biologic approved for the treatment of moderate-to-severe atopic dermatitis (AD) in children and adolescents. Previous systematic reviews explored the effectiveness and safety of dupilumab in adults with AD. However, the underlying mechanisms of AD can vary among different age groups, emphasizing the need for separate investigation into the use of dupilumab in children and adolescents with AD. OBJECTIVE: To evaluate the efficacy and safety of dupilumab in children and adolescents with AD based on evidence from clinical trials and observational studies. METHODS: The process of meta-analysis was conducted according to preferred reporting items for systematic reviews and meta-analyses guidelines. RESULTS: Seven clinical trials and 11 observational studies involving 1275 children and adolescents with AD were eligible for quantitative analysis. Overall, the pooled percentages of eczema area and severity index (EASI) 50, EASI 75, EASI 90, EASI 100, and investigator's global assessment (IGA) 0/1 were 72.9% (95% CI: 61.6%-81.9%), 57.4% (48.1%-66.2%), 31.3% (24.0%-39.7%), 29.7% (23.3%-37.0%), and 35.2% (29.3%-41.5%). With prolonged treatment time, an increase was seen in the pooled rate of EASI response, indicating that dupilumab may provide sustained benefits for children and adolescents over the long term. The reported adverse events were primarily mild and manageable, with an overall incidence rate of 7.2% across clinical trials and 7.6% across observational studies. CONCLUSION: Dupilumab was an effective and safe treatment option for children and adolescents with AD, with positive results observed from long-term use and an acceptable safety profile. More long-term, high-quality, controlled studies in different regions are needed for further verification.


Assuntos
Dermatite Atópica , Adulto , Humanos , Adolescente , Criança , Dermatite Atópica/tratamento farmacológico , Injeções Subcutâneas , Resultado do Tratamento , Índice de Gravidade de Doença , Método Duplo-Cego
12.
Molecules ; 28(18)2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37764389

RESUMO

Four previously undescribed terpenoid glucosides, including one sesquiterpenoid di-glucoside (1), two new iridoid glucosides (2, 3), and a new triterpenoid tri-glucoside (4), were isolated from a 70% ethanol extract of the root of Gentiana macrophylla (Gentianaceae), along with eight known terpenoids. Their structures were determined by spectroscopic techniques, including 1D, 2D NMR, and HRMS (ESI), as well as chemical methods. The absolute configuration of compound 1 was determined by quantum chemical calculation of its theoretical electronic circular dichroism (ECD) spectrum. The sugar moieties of all the new compounds were confirmed to be D-glucose by GC analysis after acid hydrolysis and acetylation. Anti-pulmonary inflammation activity of the iridoids were evaluated on a TNF-α induced inflammation model in A549 cells. Compound 2 could significantly alleviate the release of proinflammatory cytokines IL-1ß and IL-8 and increase the expression of anti-inflammatory cytokine IL-10.


Assuntos
Gentiana , Pneumonia , Humanos , Terpenos/farmacologia , Fator de Necrose Tumoral alfa , Glucosídeos/farmacologia , Células A549 , Citocinas , Extratos Vegetais/farmacologia
13.
Hepatology ; 74(6): 3249-3268, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34343359

RESUMO

BACKGROUND AND AIMS: Metabolic reprogramming plays an important role in tumorigenesis. However, the metabolic types of different tumors are diverse and lack in-depth study. Here, through analysis of big databases and clinical samples, we identified a carbamoyl phosphate synthetase 1 (CPS1)-deficient hepatocellular carcinoma (HCC) subtype, explored tumorigenesis mechanism of this HCC subtype, and aimed to investigate metabolic reprogramming as a target for HCC prevention. APPROACH AND RESULTS: A pan-cancer study involving differentially expressed metabolic genes of 7,764 tumor samples in 16 cancer types provided by The Cancer Genome Atlas (TCGA) demonstrated that urea cycle (UC) was liver-specific and was down-regulated in HCC. A large-scale gene expression data analysis including 2,596 HCC cases in 7 HCC cohorts from Database of HCC Expression Atlas and 17,444 HCC cases from in-house hepatectomy cohort identified a specific CPS1-deficent HCC subtype with poor clinical prognosis. In vitro and in vivo validation confirmed the crucial role of CPS1 in HCC. Liquid chromatography-mass spectrometry assay and Seahorse analysis revealed that UC disorder (UCD) led to the deceleration of the tricarboxylic acid cycle, whereas excess ammonia caused by CPS1 deficiency activated fatty acid oxidation (FAO) through phosphorylated adenosine monophosphate-activated protein kinase. Mechanistically, FAO provided sufficient ATP for cell proliferation and enhanced chemoresistance of HCC cells by activating forkhead box protein M1. Subcutaneous xenograft tumor models and patient-derived organoids were employed to identify that blocking FAO by etomoxir may provide therapeutic benefit to HCC patients with CPS1 deficiency. CONCLUSIONS: In conclusion, our results prove a direct link between UCD and cancer stemness in HCC, define a CPS1-deficient HCC subtype through big-data mining, and provide insights for therapeutics for this type of HCC through targeting FAO.


Assuntos
Carbamoil-Fosfato Sintase (Amônia)/metabolismo , Carcinoma Hepatocelular/enzimologia , Neoplasias Hepáticas/enzimologia , Animais , Carbamoil-Fosfato Sintase (Amônia)/deficiência , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Linhagem Celular Tumoral , Metilação de DNA , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Nus , Transplante de Neoplasias , Células-Tronco Neoplásicas/metabolismo , Transcriptoma , Distúrbios Congênitos do Ciclo da Ureia/enzimologia , Distúrbios Congênitos do Ciclo da Ureia/genética , Distúrbios Congênitos do Ciclo da Ureia/metabolismo , Distúrbios Congênitos do Ciclo da Ureia/patologia
14.
Opt Lett ; 47(7): 1638-1641, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35363697

RESUMO

We realize a chip-based Brillouin microlaser with remarkable features of high power and low noise using a microtoroid resonator. Our Brillouin microlaser is able to output a power of up to 126 mW with a fundamental linewidth down to 245 mHz. Additionally, in the course of Brillouin lasing we observe an intriguing power saturation-like effect, which can be attributed to complex thermo-optic-effect-induced mode mismatch between the pump and Brillouin modes. To have a quantitative understanding of this phenomenon, we develop a model by simultaneously considering Brillouin lasing and the thermo-optic effect occurring in the microcavity. Of importance, our theoretical results match well with experimentally measured data.

15.
Liver Int ; 42(1): 135-148, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34459095

RESUMO

BACKGROUND & AIMS: Preoperative obstructive jaundice is usually associated with higher post-operative mortality. Although external biliary drainage (EBD) has been widely used to relieve obstructive jaundice, the role of bile reinfusion after EBD is still controversial. The aim of our study was to study the effects of biliary obstruction, biliary drainage and bile reinfusion on bile acid metabolism and gut microbiota. METHODS: Firstly, we created a mice bile drainage collection (BDC) model to simulate the process of biliary obstruction, drainage and bile reinfusion. Then, we analysed the faecal, serum, liver and bile samples to investigate the effects of the process on bile acid profiles and gut microbiota. Finally, we evaluated the clinical effects of bile reinfusion. RESULTS: We evaluated the bile acid profiles of faeces, serum, liver and bile of normal mice. During biliary obstruction, secondary bile acids can still be produced, and increased in the liver and serum of mice. Compared with no bile reinfusion, bile reinfusion was beneficial to the recovery of T-ωMCA in the liver and bile, and can restore the colon crypt length shortened by biliary obstruction. Only Ruminococcus_1 proliferated when the biliary obstruction lasted for 12 days. In the clinic, bile reinfusion cannot accelerate the patient's perioperative recovery or prolong long-term survival. CONCLUSION: We have successfully created a mice bile drainage collection model. Short-term bile reinfusion can partially benefit the recovery of the secondary bile acids in the liver and bile, but hardly benefit the patient's perioperative recovery or long-term survival. (247 words).


Assuntos
Colestase , Microbioma Gastrointestinal , Animais , Bile , Ácidos e Sais Biliares , Drenagem , Camundongos
16.
Acta Derm Venereol ; 102: adv00635, 2022 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-34935989

RESUMO

Since the results of basic and specific classification in male androgenetic alopecia are subjective, and trichoscopic data, such as hair density and diameter distribution, are potential quantitative indicators, the aim of this study was to develop a deep learning framework for automatic trichoscopic image analysis and a quantitative model for predicting basic and specific classification in male androgenetic alopecia. A total of 2,910 trichoscopic images were collected and a deep learning framework was created on convolutional neural networks. Based on the trichoscopic data provided by the framework, correlations with basic and specific classification were analysed and a quantitative model was developed for predicting basic and specific classification using multiple ordinal logistic regression. A deep learning framework that can accurately analyse hair density and diameter distribution on trichoscopic images and a quantitative model for predicting basic and specific classification in male androgenetic alopecia were established.


Assuntos
Aprendizado Profundo , Alopecia/diagnóstico por imagem , Cabelo , Humanos , Masculino
17.
BMC Cancer ; 21(1): 33, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413231

RESUMO

BACKGROUND: Anterior gradient-2 (AGR2) is a proto-oncogene involved in tumorigenesis and cancer progression. AGR2, predominantly localized in the endoplasmic reticulum (ER), is also a secreted protein detected in the extracellular compartment in multiple cancers. However, the biological functions of intracellular and extracellular AGR2 remain to be elucidated. METHODS: Based on the biochemical structure of AGR2 protein, PANC-1 pancreatic cancer cells stably expressing ER-resident or secreted AGR2 were generated by a lentivirus-mediated stable overexpression system. The capacities of cell proliferation, migration, invasion and survival were assessed in PANC-1 stable cells. Moreover, EGFR expression and activation were determined to explore the possible mechanism of AGR2 roles in pancreatic cancer tumorigenesis. RESULTS: It was discovered that secreted AGR2, but not ER-resident AGR2, promotes cell proliferation, migration and invasion of PANC-1 cells. Moreover, the data indicated that both the ER-resident and the secreted AGR2 enhance the survival capacity of PANC-1 cells after tunicamycin-induced ER stress and gemcitabine treatment. However, EGFR expression and activation were not found to be involved in AGR2-dependent oncogenic phenotypes in PANC-1 cells. CONCLUSIONS: Secreted AGR2 is predominantly involved in cell proliferation, migration and invasion in PANC-1 pancreatic cancer cells. Both secreted and ER-resident AGR2 contribute to the survival of PANC-1 cells under the challenging conditions. These findings provide insight into how different localizations of AGR2 have contributed to pancreatic cancer growth, metastasis, and drug sensitivity.


Assuntos
Movimento Celular , Proliferação de Células , Desoxicitidina/análogos & derivados , Retículo Endoplasmático/patologia , Regulação Neoplásica da Expressão Gênica , Mucoproteínas/metabolismo , Proteínas Oncogênicas/metabolismo , Neoplasias Pancreáticas/patologia , Antimetabólitos Antineoplásicos/farmacologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Desoxicitidina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Estresse do Retículo Endoplasmático , Humanos , Mucoproteínas/genética , Invasividade Neoplásica , Proteínas Oncogênicas/genética , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Proto-Oncogene Mas , Células Tumorais Cultivadas , Gencitabina
18.
J Environ Manage ; 299: 113607, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34467864

RESUMO

Traditional Chinese medicine (TCM) has wide application and important functions in curing many diseases, but a great number of herb residues are usually generated after its manufacture and usage. Without proper and timely treatment, these traditional Chinese medicinal herb (TCMH) residues will cause some environmental pollution. In addition to treatment, bioresources utilization of TCMH residues is also important for its great potential as a suitable feedstock for the production of energy, materials, and chemicals. In this situation, advanced and well-designed solid waste management is important to make the TCM industry environmentally friendly and economically attractive. In this review article, the recent progress focusing on various methods for TCMH residues treatment and bioresources utilization are introduced in detail. In particular, the technologies for thermochemical conversion and biochemical conversion of TCMH residues are mainly focused on in order to show how to fulfill effective and efficient bioresources utilization. Besides, some other technologies which are suitable for the treatment and bioresources utilization of TCMH residues are presented as well. Finally, some industrial prospects are given from the economic, operational, and environmental aspects for the further development of treatment and bioresources utilization of TCMH residues. Overall, this work can provide some systematical and comprehensive information for the development of technologies that help sustainably manage the herb residues generated in the TCM industry.


Assuntos
Plantas Medicinais , China , Medicina Tradicional Chinesa
19.
Cancer ; 126(10): 2163-2173, 2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-32125701

RESUMO

BACKGROUND: The current study was performed to investigate whether circulating cell-free Epstein-Barr virus DNA (cfEBV DNA) would be useful for posttreatment surveillance in patients with nasopharyngeal carcinoma (NPC). METHODS: The authors identified a total of 1984 nondisseminated NPC patients from an institutional big-data research platform. Blood samples were collected within 3 months of the completion of radiotherapy and every 3 to 12 months thereafter for cfEBV DNA analysis. Patients were followed until disease recurrence was detected or for a median of 60 months. Diagnostic performance was assessed by calculating the sensitivity, specificity, and accuracy based on the clinical detection of disease recurrence by conventional surveillance modalities (imaging scans and pathological examination). RESULTS: During follow-up, a total of 767 patients (38.7%) had detectable cfEBV DNA. The recurrence rate among these patients was 63.8% (489 of 767 patients), which was significantly higher than that in patients with undetectable cfEBV DNA (8.6%; 105 of 1217 patients). cfEBV DNA sensitivity, specificity, and accuracy were 68.8%, 80.0%, and 78.2%, respectively, for local recurrence; 80.2%, 80.0%, and 85.9%, respectively, for regional recurrence; and 91.1%, 80.0%, and 92.8%, respectively, for distant metastasis. cfEBV DNA was found to have higher sensitivity for the detection of extrapulmonary metastases (94.9%-96.5%) compared with pulmonary metastases (78.4%). It is interesting to note that among the patients with disease recurrence with detectable cfEBV DNA, positive cfEBV DNA results preceded radiological and/or clinical evidence of disease recurrence by a median of 2.3 months (interquartile range, 0.1-9.5 months). In addition, of the 278 cfEBV DNA-positive patients who did not develop disease recurrence, 227 (81.7%) had transiently positive cfEBV DNA that fell to undetectable levels during long-term monitoring. CONCLUSIONS: Plasma cfEBV DNA in patients with NPC appears to be an early sign of tumor recurrence, especially extrapulmonary metastases.


Assuntos
DNA Viral/sangue , Infecções por Vírus Epstein-Barr/epidemiologia , Herpesvirus Humano 4/genética , Carcinoma Nasofaríngeo/virologia , Neoplasias Nasofaríngeas/virologia , Recidiva Local de Neoplasia/virologia , Adulto , Bases de Dados Factuais , Infecções por Vírus Epstein-Barr/radioterapia , Feminino , Humanos , Incidência , Biópsia Líquida , Masculino , Carcinoma Nasofaríngeo/epidemiologia , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/epidemiologia , Neoplasias Nasofaríngeas/radioterapia , Metástase Neoplásica , Recidiva Local de Neoplasia/epidemiologia , Vigilância da População , Prognóstico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
20.
PLoS One ; 19(2): e0297096, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38306332

RESUMO

BACKGROUND: Adults living alone represent a growing population group in China. Understanding the prevalence of body mass index (BMI) categories and their associations with demographic and lifestyle factors among this group is essential for informing targeted interventions and public health policies. METHODS: In this population-based cross-sectional study, we used individual-level data from the 2011-2021 China General Social Survey. Main outcomes were prevalence of BMI categories adjusted for gender and age, using logistic regression and model-predicted marginal prevalence to estimate BMI categories prevalence. RESULTS: We analyzed 9,077 single-living Chinese adult participants. The primary-adjusted prevalence of BMI categories varied across different genders and age groups. Underweight was more prevalent in females (12.73%; 95% CI: 12.31% - 13.14%) than in males (7.54%; 95% CI: 7.19% - 7.88%), while overweight and obesity were higher in males. Primary-adjusted underweight prevalence was highest among the 18-24 years age group (22.09%; 95% CI: 20.17% - 24.01%) and decreased with age. Primary-adjusted overweight prevalence increased with age, peaking in the 45-54 years age group (41.94%; 95% CI: 40.96% - 42.93%). Primary-adjusted obesity prevalence exhibited a fluctuating pattern across age groups, with the highest prevalence observed in the 45-54 years age group (9.81%; 95% CI: 9.19% - 10.44%). CONCLUSION: Our findings reveal significant associations between BMI categories and demographic and lifestyle factors among adults living alone in China. These results can inform targeted interventions and public health policies aimed at promoting healthy weight management and addressing the unique health challenges faced by single-living individuals in China.


Assuntos
Sobrepeso , Magreza , Adulto , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Sobrepeso/epidemiologia , Índice de Massa Corporal , Magreza/epidemiologia , Prevalência , Estudos Transversais , Ambiente Domiciliar , Obesidade/epidemiologia , China/epidemiologia , Fatores de Risco
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