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1.
Theor Appl Genet ; 137(3): 51, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38369666

RESUMO

KEY MESSAGE: ClLOX, is located on chromosome 2 and encodes a lipoxygenase gene, which induced watermelon powdery mildew resistance by inhibiting pathogen spread. Powdery mildew is one of the most severe fungal diseases reducing yield and quality of watermelon (Citrullus lanatus L.) and other cucurbit crops. Genes responsible for powdery mildew resistance in watermelon are highly valuable. In this study, we first identified the QTL pm-lox for powdery mildew resistance in watermelon, located within a 0.93 Mb interval of chromosome 2, via XP-GWAS method using two F2 populations. The F2:3 families from one of the F2 populations were then used for fine-mapping the pm-lox locus into a 9,883 bp physical region between 29,581,906 and 29,591,789, containing only two annotated genes. Of these, only ClG42_02g0161300 showed a significant differential expression between the resistant and susceptible lines after powdery mildew inoculation based on RNA sequencing (RNA-seq) and qRT-PCR analysis, and is designated ClLOX. Derived Cleaved Amplified Polymorphic Sequence (dCAPs) markers were developed and validated. In addition, our tests showed that the resistance was anti-spread rather than anti-infection of the pathogen. This study identified a new resistance gene (ClLOX), provided insights into the mechanism of powdery mildew resistance, and developed a molecular marker for watermelon breeding.


Assuntos
Ascomicetos , Citrullus , Humanos , Mapeamento Cromossômico/métodos , Resistência à Doença/genética , Citrullus/genética , Citrullus/microbiologia , Ascomicetos/genética , Melhoramento Vegetal , Doenças das Plantas/genética , Doenças das Plantas/microbiologia
2.
Anticancer Drugs ; 34(8): 954-961, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36800249

RESUMO

The development of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) represents a paradigm shift in the treatment of lung cancer with EGFR mutations. Aumolertinib has been shown to be a safe agent in the registry study. However, successful rechallenge with aumolertinib following osimertinib-induced myocardial damage has not been reported. In this article, a case of neoadjuvant therapy for lung adenocarcinoma is retrospectively analyzed, and the relevant literature is reviewed. The patient was diagnosed with stage IIIA lung adenocarcinoma, and genetic testing revealed EGFR exon 19 deletion mutation combined with Tumor Protein p53 (TP53) mutation. The mutation abundance is 33.5 and 14%, respectively. One month after osimertinib treatment, the patient developed myocardial damage, and abnormal indicators such as myocardial enzyme spectrum showed abnormalities and cardiac insufficiency, followed by pulmonary hypertension and pulmonary edema. Aumolertinib was subsequently used for treatment, following which the myocardial enzyme spectrum returned to normal, and the symptoms of bilateral interstitial edema disappeared. In addition to the disappearance of adverse reactions, the therapeutic effect was excellent; the lung lesions and mediastinal lymph nodes were significantly reduced, and the operation was successfully conducted. This is the first report of successful neoadjuvant treatment of EGFR exon 19 deletion combined with TP53 mutation in NSCLC using aumolertinib after osimertinib-induced myocardial damage. The results suggested that aumolertinib had fewer adverse reactions in patients with EGFR exon 19 deletion combined with TP53 mutation, and aumolertinib may be a potential neoadjuvant therapy for stage IIIA lung cancer.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Terapia Neoadjuvante , Estudos Retrospectivos , Proteína Supressora de Tumor p53/genética , Receptores ErbB/genética , Inibidores de Proteínas Quinases/efeitos adversos , Compostos de Anilina/efeitos adversos , Mutação , Adenocarcinoma de Pulmão/tratamento farmacológico , Éxons
3.
J Org Chem ; 88(1): 341-346, 2023 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-36516983

RESUMO

A CuI-catalyzed C-N coupling reaction of 3-bromo-DMAP with l-prolinamides was conducted at 80 °C in 12-16 h, where the prolinamide's structure had an accelerating effect on the Ullmann-type reaction. This reaction was used to construct chiral 3-amino DMAP catalysts. Furthermore, enantioenriched DMAP analogue C8 was applied in an asymmetric Black rearrangement of 2-benzofuranylcarbonates, affording 3,3-disubstituted benzofuran-2-ones in up to 96% yield and 97% ee.


Assuntos
Prolina , Estrutura Molecular , Estereoisomerismo , Catálise
4.
Radiol Med ; 128(9): 1079-1092, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37486526

RESUMO

PURPOSE: Lung cancer has significant genetic and phenotypic heterogeneity, leading to poor prognosis. Radiomic features have emerged as promising predictors of the tumor phenotype. However, the role of underlying information surrounding the cancer remains unclear. MATERIALS AND METHODS: We conducted a retrospective study of 508 patients with NSCLC from three institutions. Radiomics models were built using features from six tumor regions and seven classifiers to predict three prognostically significant tumor phenotypes. The models were evaluated and interpreted by the mean area under the receiver operating characteristic curve (AUC) under nested cross-validation and Shapley values. The best-performing predictive models corresponding to six tumor regions and three tumor phenotypes were identified for further comparative analysis. In addition, we designed five experiments with different voxel spacing to assess the sensitivity of the experimental results to the spatial resolution of the voxels. RESULTS: Our results demonstrated that models based on 2D, 3D, and peritumoral region features yielded mean AUCs and 95% confidence intervals of 0.759 and [0.747-0.771] for lymphovascular invasion, 0.889 and [0.882-0.896] for pleural invasion, and 0.839 and [0.829-0.849] for T-staging in the testing cohort, which was significantly higher than all other models. Similar results were obtained for the model combining the three regional features at five voxel spacings. CONCLUSION: Our study revealed the predictive role of the developed methods with multi-regional features for the preoperative assessment of prognostic factors in NSCLC. The analysis of different voxel spacing and model interpretability strengthens the experimental findings and contributes to understanding the biological significance of the radiological phenotype.

5.
Mikrochim Acta ; 189(4): 158, 2022 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-35347486

RESUMO

A rapid and convenient fluorescence glyphosate (GLYP) biosensor was developed based on DNA-templated copper nanoparticles (DNA-CuNPs). In the absence of GLYP, the DNA-CuNPs were formed through the reduction of Cu2+ by vitamin C (Vc). The DNA-CuNPs emitted intense fluorescence at 615 nm when being excited at 340 nm. In the presence of GLYP, GLYP can strongly chelate with Cu2+ by the phosphate and carboxyl groups to decrease the amount of free Cu2+. Due to the lack of free Cu2+, DNA-CuNPs cannot be formed, which caused the fluorescence to decrease. The whole detection process of this proposed GLYP biosensor can be completed within 14 min. Titration experiments showed that this biosensor had a linear relationship for GLYP in the range 1 to 18 µM with a limit of detection (LOD) of 0.47 µM. This biosensor showed obvious selectivity among other pesticides, even between GLYP and organophosphorus pesticides. This biosensor performed well for GLYP detection in real samples with recoveries of 88.0-104.0%.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Praguicidas , Cobre , DNA , Glicina/análogos & derivados , Compostos Organofosforados , Glifosato
6.
J Vasc Res ; 57(4): 185-194, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32526735

RESUMO

Information on the function of transient receptor potential vanilloid 1 (TRPV1) in arteriogenesis is limited. We aimed to verify whether TRPV1 is involved in collateral vessel growth in rat hind limbs and elucidate the possible subcellular action mechanisms. Adult Sprague Dawley rats were chosen to establish the hind limb ischemic model and treatment with capsaicin. Angiographies were performed, and tissue was isolated for immunohistochemistry. In vitro, rat aortic endothelial cells (RAECs) were treated with capsaicin and antagonist capsazepine. The RAEC proliferation was determined, and the protein and mRNA levels of Ca2+-dependent transcription factors were assessed. In vivo, the collateral vessels exhibited positive outward remodeling characterized by enhanced inflammatory cell/macrophage accumulation in the adventitia and activated cell proliferation in all layers of the vascular wall and elevated endothelial NO synthetase expression in the rats with hind limb ligation. In RAECs, TRPV1 activation-induced Ca2+-dependent transcriptional factors, nuclear factor of activated T cells 1, calsenilin and myocyte enhancer factor 2C increase, and augmented RAEC proliferation could be a subcellular mechanism for TRPV1 in endothelial cells and ultimately contribute to collateral vessel growth. TRPV1, a novel candidate, positively regulates arteriogenesis, meriting further studies to unravel the potential therapeutic target leading to improved collateral vessel growth for treating ischemic diseases.


Assuntos
Indutores da Angiogênese/farmacologia , Artérias/efeitos dos fármacos , Capsaicina/farmacologia , Circulação Colateral/efeitos dos fármacos , Isquemia/tratamento farmacológico , Músculo Esquelético/irrigação sanguínea , Neovascularização Fisiológica/efeitos dos fármacos , Canais de Cátion TRPV/agonistas , Animais , Artérias/metabolismo , Artérias/fisiopatologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Membro Posterior , Isquemia/metabolismo , Isquemia/fisiopatologia , Proteínas Interatuantes com Canais de Kv/metabolismo , Fatores de Transcrição MEF2/metabolismo , Fatores de Transcrição NFATC/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Ratos Sprague-Dawley , Fluxo Sanguíneo Regional , Transdução de Sinais , Canais de Cátion TRPV/metabolismo
7.
Med Sci Monit ; 26: e921831, 2020 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-32623439

RESUMO

BACKGROUND Insomnia seriously affects people's health and quality of life. Short-term use of Western drugs may also be harmful. Traditional Chinese medicine has been widely used to treat diseases in world. Therefore, this paper aims to study the therapeutic effect of berberine based on the insomnious rat model. MATERIAL AND METHODS The insomnia rat model was established by intragastric administration of caffeine and parachlorophenylalanine (PCPA). Berberine and diazepam were used to treat the established insomnia rats. Then, the pathological changes of insomnia rats were detected. In addition, transcriptome sequencing and data analysis were carried out using rat hippocampus. The expression of key genes was verified by quantitative polymerase chain reaction and western blot. RESULTS After 7 days of intragastric administration of berberine, the body weight, memory, and sleep quality of insomnia rats were significantly improved. The key roles of Erbb4, Erbb2, Ar, and Grin2a in berberine treatment were identified. Through the analysis of biological functions and signaling pathways, berberine was shown to play a salutary role through nervous system development and ErbB signaling pathway. Gene-set enrichment analysis (GSEA) results showed that berberine treatment affected more metabolic pathways. Compared with diazepam, berberine can play a faster role, and also improve the overall health level of insomnia rats. CONCLUSIONS These results suggest that berberine can alleviate insomnia in rats through a neuroprotective effect and improved metabolic level. Berberine has great potential in treatment of insomnia and might have better clinical significance.


Assuntos
Berberina/farmacologia , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Animais , Berberina/metabolismo , Modelos Animais de Doenças , Masculino , Medicina Tradicional Chinesa , Memória , Redes e Vias Metabólicas , Qualidade de Vida , Ratos , Ratos Sprague-Dawley , Receptor ErbB-2/metabolismo , Receptor ErbB-4/metabolismo , Receptores Androgênicos/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Transdução de Sinais/efeitos dos fármacos
8.
Plant Biotechnol J ; 17(12): 2246-2258, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31022325

RESUMO

Years of selection for desirable fruit quality traits in dessert watermelon (Citrullus lanatus) has resulted in a narrow genetic base in modern cultivars. Development of novel genomic and genetic resources offers great potential to expand genetic diversity and improve important traits in watermelon. Here, we report a high-quality genome sequence of watermelon cultivar 'Charleston Gray', a principal American dessert watermelon, to complement the existing reference genome from '97103', an East Asian cultivar. Comparative analyses between genomes of 'Charleston Gray' and '97103' revealed genomic variants that may underlie phenotypic differences between the two cultivars. We then genotyped 1365 watermelon plant introduction (PI) lines maintained at the U.S. National Plant Germplasm System using genotyping-by-sequencing (GBS). These PI lines were collected throughout the world and belong to three Citrullus species, C. lanatus, C. mucosospermus and C. amarus. Approximately 25 000 high-quality single nucleotide polymorphisms (SNPs) were derived from the GBS data using the 'Charleston Gray' genome as the reference. Population genomic analyses using these SNPs discovered a close relationship between C. lanatus and C. mucosospermus and identified four major groups in these two species correlated to their geographic locations. Citrullus amarus was found to have a distinct genetic makeup compared to C. lanatus and C. mucosospermus. The SNPs also enabled identification of genomic regions associated with important fruit quality and disease resistance traits through genome-wide association studies. The high-quality 'Charleston Gray' genome and the genotyping data of this large collection of watermelon accessions provide valuable resources for facilitating watermelon research, breeding and improvement.


Assuntos
Citrullus/genética , Genoma de Planta , Mapeamento Cromossômico , Resistência à Doença , Frutas , Estudos de Associação Genética , Genômica , Polimorfismo de Nucleotídeo Único
10.
Lasers Surg Med ; 51(3): 251-255, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30575079

RESUMO

OBJECTIVE: To evaluate the efficacy of the multisource radiofrequency in periorbital wrinkles treatment using a VISIA imager. METHODS: This is a prospective cohort study involving 30 sites in 15 patients. INCLUSION CRITERIA: healthy subjects with periorbital wrinkles. Patients underwent five treatment sessions for each site using multisource radiofrequency. VISIA imager was used before and after each treatment, and in 12-week follow-up. The wrinkle scores were calculated and compared between baseline and 12-week follow-up. Changing in periorbital wrinkles were evaluated by blinded dermatologist using a scale of 0-3. After the study, patients rated their satisfaction using a scale of 0-3. The study protocol was approved by our institutional human research review committee, according to the ethics guideline of Helsinki (1975). RESULTS: The effect of treatment on subjects on follow-up compared to baseline showed a highly significant difference with P-values <0.05. Only two patients had no improvement according to blind dermatologist assessment of photographs. Thirteen patients reported satisfaction scale between 1 and 3. CONCLUSIONS: The multisource radiofrequency is safe and effective in reducing periorbital rhytids, and with the help of VISIA imager we can get more objective data to evaluate the efficacy of radiofrequency treatment on the periorbital areas. Lasers Surg. Med. 51:251-255, 2019. © 2018 Wiley Periodicals, Inc.


Assuntos
Técnicas Cosméticas , Face , Terapia por Radiofrequência , Envelhecimento da Pele/efeitos da radiação , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Estudos Prospectivos , Resultado do Tratamento
11.
Molecules ; 24(10)2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-31108895

RESUMO

Kanamycin is an aminoglycoside antibiotic widely used in treating animal diseases caused by Gram-negative and Gram-positive infections. Kanamycin has a relatively narrow therapeutic index, and can accumulate in the human body through the food chain. The abuse of kanamycin can have serious side-effects. Therefore, it was necessary to develop a sensitive and selective analysis method to detect kanamycin residue in food to ensure public health. There are many analytical methods to determine kanamycin concentration, among which high performance liquid chromatography (HPLC) is a common and practical tool. This paper presents a review of the application of HPLC analysis of kanamycin in different sample matrices. The different detectors coupled with HPLC, including Ultraviolet (UV)/Fluorescence, Evaporative Light Scattering Detector (ELSD)/Pulsed Electrochemical Detection (PED), and Mass Spectrometry, are discussed. Meanwhile, the strengths and weaknesses of each method are compared. The pre-treatment methods of food samples, including protein precipitation, liquid-liquid extraction (LLE), and solid-phase extraction (SPE) are also summarized in this paper.


Assuntos
Antibacterianos/análise , Análise de Alimentos/métodos , Canamicina/análise , Animais , Fracionamento Químico , Cromatografia Líquida de Alta Pressão , Cadeia Alimentar , Humanos
12.
Clin Lab ; 64(6): 1021-1030, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29945306

RESUMO

BACKGROUND: The increase in the prevalence of drug-resistant Acinetobacter baumannii is a serious public health concern, which is closely linked to the formation of biofilm. It is reported that the bacteriophage and its endolysin have a good ability to degrade biofilms. The goals of this study were to compare the ability of A. baumannii bacteriophage AB3, its endolysin AB3, and three antibiotics to degrade A. baumannii biofilm and biofilm-bound A. baumannii and to understand the antibacterial mechanism of LysAB3. METHODS: The 558-bp sequence of the LysAB3 gene was amplified by polymerase chain reaction (PCR); the fragment was cloned into pET28a (+) to construct the recombinant plasmid pET28a-LysAB3, which was then expressed in E. coli BL21 (DE3) to obtain the LysAB3. Differences in A. baumannii biofilm and biofilm-bound A. baumannii after treatment with bacteriophage AB3, LysAB3 or three antibiotics were examined using the crystal violet staining method and an MTT (3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide) assay. Changes in biofilm morphology and thickness in each treatment group were observed by laser scanning confocal microscopy. In addition, a LysAB3 construct with the amphiphilic peptide structural region removed (LysAB3-D) was assessed for its antibacterial activity. RESULTS: After 24-hour treatment with either bacteriophage AB3 and its LysAB3, A. baumannii biofilms were significantly degraded, and the number of viable biofilm-bound A. baumannii were also significantly decreased. After removing the amphiphilic peptide structure motif from LysAB3, the antibacterial activity decreased from 95.8% to 33.3%. CONCLUSIONS: Thus, LysAB3 can effectively degrade A. baumannii biofilm and biofilm-bound A. baumannii in vitro. The antibacterial mechanism of LysAB3 may be associated with the ability of the amphiphilic peptide structural region to enhance the permeability of cytoplasmic membrane of A. baumannii by degradation of bacterial wall peptidoglycan.


Assuntos
Acinetobacter baumannii/fisiologia , Bacteriófagos/metabolismo , Biofilmes/crescimento & desenvolvimento , Endopeptidases/metabolismo , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/virologia , Antibacterianos/farmacologia , Bacteriófagos/genética , Bacteriófagos/fisiologia , Biofilmes/efeitos dos fármacos , Endopeptidases/genética , Escherichia coli/genética , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacologia
13.
Clin Invest Med ; 39(4): E120-31, 2016 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-27619399

RESUMO

PURPOSE: Some previous studies have found that continued metformin use is beneficial in the management of polycystic ovary syndrome (PCOS) in pregnant women. A systemic review and meta-analysis were needed to more fully assess the effects of metformin on pregnant PCOS patients. METHODS: The literature was fully searched using MEDLINE, EMBASE, SCOPUS, and COCHRANE for continued metformin use during pregnancy in women with PCOS. A systematic review and meta-analysis were performed to evaluate the comprehensive effects of continued metformin treatment on pregnancy-related outcomes in these women. RESULTS: Eleven eligible studies out of 127 relevant publications were included in meta-analysis. The rates of early pregnancy loss and preterm delivery were found to be significantly decreased in metformin-treated PCOS women. A non-significant difference was found in fetal abnormality and fetal birth weight between the metformin-treated and the non-treated groups. The incidence of gestational diabetes mellitus (GDM) and hypertension/preeclampsia were not significantly different in the two groups, probably because of inconsistent results in the subgroup analysis. CONCLUSIONS: Our results showed that continued use during of metformin, during pregnancy in women with PCOS, had no effect on incidence of fetal abnormalities or fetal birth weight. The effects of metformin on GDM and hypertension/preeclampsia should be determined through high-quality randomized controlled trials.


Assuntos
Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Complicações na Gravidez , Aborto Espontâneo , Peso ao Nascer , Diabetes Gestacional/terapia , Medicina Baseada em Evidências , Feminino , Humanos , Hipertensão , Pré-Eclâmpsia/terapia , Gravidez , Resultado da Gravidez , Nascimento Prematuro
14.
PLoS One ; 19(3): e0299821, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38517864

RESUMO

Pancreatic ß-cell failure is a pathological feature in type 1 diabetes. One promising approach involves inducing transdifferentiation of related pancreatic cell types, specifically α cells that produce glucagon. The chemokine stromal cell-derived factor-1 alpha (SDF-1α) is implicated in pancreatic α-to-ß like cell transition. Here, the serum level of SDF-1α was lower in T1D with C-peptide loss, the miR-23a was negatively correlated with SDF-1α. We discovered that exosomal miR-23a, secreted from ß cells, functionally downregulates the expression of SDF-1α, leading to increased Pax4 expression and decreased Arx expression in vivo. Adenovirus-vectored miR-23a sponge and mimic were constructed to further explored the miR-23a on pancreatic α-to-ß like cell transition in vitro, which yielded results consistent with our cell-based assays. Suppression of miR-23a upregulated insulin level and downregulated glucagon level in STZ-induced diabetes mice models, effectively promoting α-to-ß like cell transition. Our findings highlight miR-23a as a new therapeutic target for regenerating pancreatic ß cells from α cells.


Assuntos
Células Secretoras de Glucagon , Células Secretoras de Insulina , MicroRNAs , Animais , Camundongos , Transdiferenciação Celular/genética , Quimiocina CXCL12/genética , Quimiocina CXCL12/metabolismo , Glucagon , Células Secretoras de Glucagon/metabolismo , Células Secretoras de Insulina/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo
15.
J Clin Hypertens (Greenwich) ; 26(7): 757-764, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38687184

RESUMO

The prevalence of isolated systolic hypertension (ISH) has doubled between 2002-2005 and 2014 among the oldest-old population in China. However, the prevalence and characteristics of ISH among the oldest-old population in southwestern China remain less known. This study aimed to investigate the prevalence of ISH among the oldest-old population in Chengdu and identify associated factors to provide valuable information for disease etiology and prevention. We recruited 1,312 participants aged over 80 years by using a stratified cluster sampling method between September 2015 and June 2016, from three districts (Jinjiang, Qingyang, and Longquanyi) of Chengdu, the largest city of southwest China. A structured questionnaire, anthropometric data, and blood pressure were collected according to the standard method. Blood pressure was measured three times by using a standardized mercury sphygmomanometer after a 10-minute seated rest. Of 1312 participants, 53.0% (n = 695) had ISH. The prevalence of ISH in men and women was 54.7% and 51.3%, respectively, with no significant sex difference (P = .222). The prevalence of ISH increased with advanced age in men (P for trend = 0.029), 52.5% for the 80-84 years group, 55.2% for the 85-89 years group, and 70.4% for the 90-98 years group, respectively. Multivariable logistic regression analyses found that drinking (OR = 1.85, 95%CI = 1.26-2.71), being overweight (OR = 1.88, 95%CI = 1.19-2.96), and having a higher heart rate (OR = 0.66, 95%CI = 0.51-0.86) were associated with ISH. Stratified by sex, these three factors remained significant in men. Our work highlights that the burden of ISH is substantial among the oldest-old population in southwestern China.


Assuntos
Pressão Sanguínea , Hipertensão , Humanos , Masculino , Feminino , China/epidemiologia , Prevalência , Hipertensão/epidemiologia , Estudos Transversais , Fatores de Risco , Idoso de 80 Anos ou mais , Pressão Sanguínea/fisiologia , Determinação da Pressão Arterial/métodos , Determinação da Pressão Arterial/estatística & dados numéricos , Inquéritos e Questionários , Hipertensão Sistólica Isolada
16.
Radiother Oncol ; 191: 110082, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38195018

RESUMO

BACKGROUND: Selecting therapeutic strategies for cancer patients is typically based on key target-molecule biomarkers that play an important role in cancer onset, progression, and prognosis. Thus, there is a pressing need for novel biomarkers that can be utilized longitudinally to guide treatment selection. METHODS: Using data from 508 non-small cell lung cancer (NSCLC) patients across three institutions, we developed and validated a comprehensive predictive biomarker that distinguishes six genotypes and infiltrative immune phenotypes. These features were analyzed to establish the association between radiological phenotypes and tumor genotypes/immune phenotypes and to create a radiological interpretation of molecular features. In addition, we assessed the sensitivity of the models by evaluating their performance at five different voxel intervals, resulting in improved generalizability of the proposed approach. FINDINGS: The radiomics model we developed, which integrates clinical factors and multi-regional features, outperformed the conventional model that only uses clinical and intratumoral features. Our combined model showed significant performance for EGFR, KRAS, ALK, TP53, PIK3CA, and ROS1 mutation status with AUCs of 0.866, 0.874, 0.902, 0.850, 0.860, and 0.900, respectively. Additionally, the predictive performance for PD-1/PD-L1 was 0.852. Although the performance of all models decreased to different degrees at five different voxel space resolutions, the performance advantage of the combined model did not change. CONCLUSIONS: We validated multiscale radiomic signatures across tumor genotypes and immunophenotypes in a multi-institutional cohort. This imaging-based biomarker offers a non-invasive approach to select patients with NSCLC who are sensitive to targeted therapies or immunotherapy, which is promising for developing personalized treatment strategies during therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Proteínas Tirosina Quinases , Radiômica , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/uso terapêutico , Biomarcadores
17.
Biomark Res ; 12(1): 12, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38273398

RESUMO

BACKGROUND: Accurate prediction of tumor molecular alterations is vital for optimizing cancer treatment. Traditional tissue-based approaches encounter limitations due to invasiveness, heterogeneity, and molecular dynamic changes. We aim to develop and validate a deep learning radiomics framework to obtain imaging features that reflect various molecular changes, aiding first-line treatment decisions for cancer patients. METHODS: We conducted a retrospective study involving 508 NSCLC patients from three institutions, incorporating CT images and clinicopathologic data. Two radiomic scores and a deep network feature were constructed on three data sources in the 3D tumor region. Using these features, we developed and validated the 'Deep-RadScore,' a deep learning radiomics model to predict prognostic factors, gene mutations, and immune molecule expression levels. FINDINGS: The Deep-RadScore exhibits strong discrimination for tumor molecular features. In the independent test cohort, it achieved impressive AUCs: 0.889 for lymphovascular invasion, 0.903 for pleural invasion, 0.894 for T staging; 0.884 for EGFR and ALK, 0.896 for KRAS and PIK3CA, 0.889 for TP53, 0.895 for ROS1; and 0.893 for PD-1/PD-L1. Fusing features yielded optimal predictive power, surpassing any single imaging feature. Correlation and interpretability analyses confirmed the effectiveness of customized deep network features in capturing additional imaging phenotypes beyond known radiomic features. INTERPRETATION: This proof-of-concept framework demonstrates that new biomarkers across imaging features and molecular phenotypes can be provided by fusing radiomic features and deep network features from multiple data sources. This holds the potential to offer valuable insights for radiological phenotyping in characterizing diverse tumor molecular alterations, thereby advancing the pursuit of non-invasive personalized treatment for NSCLC patients.

18.
Nat Genet ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38977857

RESUMO

To decipher the genetic diversity within the cucurbit genus Citrullus, we generated telomere-to-telomere (T2T) assemblies of 27 distinct genotypes, encompassing all seven Citrullus species. This T2T super-pangenome has expanded the previously published reference genome, T2T-G42, by adding 399.2 Mb and 11,225 genes. Comparative analysis has unveiled gene variants and structural variations (SVs), shedding light on watermelon evolution and domestication processes that enhanced attributes such as bitterness and sugar content while compromising disease resistance. Multidisease-resistant loci from Citrullus amarus and Citrullus mucosospermus were successfully introduced into cultivated Citrullus lanatus. The SVs identified in C. lanatus have not only been inherited from cordophanus but also from C. mucosospermus, suggesting additional ancestors beyond cordophanus in the lineage of cultivated watermelon. Our investigation substantially improves the comprehension of watermelon genome diversity, furnishing comprehensive reference genomes for all Citrullus species. This advancement aids in the exploration and genetic enhancement of watermelon using its wild relatives.

19.
Nat Commun ; 15(1): 4295, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769327

RESUMO

Chili pepper (Capsicum) is known for its unique fruit pungency due to the presence of capsaicinoids. The evolutionary history of capsaicinoid biosynthesis and the mechanism of their tissue specificity remain obscure due to the lack of high-quality Capsicum genomes. Here, we report two telomere-to-telomere (T2T) gap-free genomes of C. annuum and its wild nonpungent relative C. rhomboideum to investigate the evolution of fruit pungency in chili peppers. We precisely delineate Capsicum centromeres, which lack high-copy tandem repeats but are extensively invaded by CRM retrotransposons. Through phylogenomic analyses, we estimate the evolutionary timing of capsaicinoid biosynthesis. We reveal disrupted coding and regulatory regions of key biosynthesis genes in nonpungent species. We also find conserved placenta-specific accessible chromatin regions, which likely allow for tissue-specific biosynthetic gene coregulation and capsaicinoid accumulation. These T2T genomic resources will accelerate chili pepper genetic improvement and help to understand Capsicum genome evolution.


Assuntos
Capsaicina , Capsicum , Evolução Molecular , Genoma de Planta , Filogenia , Telômero , Capsicum/genética , Capsicum/metabolismo , Capsaicina/metabolismo , Telômero/genética , Telômero/metabolismo , Frutas/genética , Frutas/metabolismo , Retroelementos/genética , Regulação da Expressão Gênica de Plantas
20.
Medicine (Baltimore) ; 102(50): e36251, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38115334

RESUMO

RATIONALE: Adult-onset Still's disease (AOSD) is a rare multisystem disorder considered a complex autoinflammatory syndrome. The clinical and biological features of AOSD typically include a high fever with arthritic symptoms, evanescent skin rash, sore throat, striking neutrophilic leukocytosis, hyperferritinemia, and abnormal liver function. The typical rash and fever are important diagnostic clues for AOSD. Here, we report a case of atypical rash manifesting as persistent itchy urticaria. PATIENT CONCERNS: A 57-year-old female presented with a 6-day history of fever. During her hospital stay, she progressively developed rashes that were not associated with fever, primarily distributed on her back and the distal extremities, and associated with pronounced itching. The rash was initially suspected to be urticaria; however, the patient exhibited a poor response to antihistamines. After malignancies and other rheumatic diseases were excluded, the diagnosis leaned towards AOSD based on diagnostic criteria. The patient's fever was well controlled with the initiation of glucocorticoids, and no further rashes were observed. DIAGNOSES: Although the patient exhibited atypical rashes, after ruling out malignancies and other rheumatic diseases, she met 2 major and 3 minor criteria. Based on Yamaguchi's criteria, the patient was diagnosed with AOSD. INTERVENTIONS: Initially, the patient was administered an intravenous infusion of methylprednisolone at 40 mg once daily. This was later transitioned to oral administration with gradual dose reduction. OUTCOMES: Follow-up at 1 year showed no recurrence of the rash, with a stable condition and no relapse. LESSONS: This case provides valuable insights for the early diagnosis of AOSD, emphasizing the importance of considering this diagnosis even when presenting with atypical skin rash.


Assuntos
Exantema , Neoplasias , Doença de Still de Início Tardio , Urticária , Feminino , Humanos , Pessoa de Meia-Idade , Exantema/complicações , Febre/complicações , Neoplasias/complicações , Prurido , Doença de Still de Início Tardio/complicações , Doença de Still de Início Tardio/diagnóstico , Doença de Still de Início Tardio/tratamento farmacológico , Urticária/diagnóstico , Urticária/etiologia
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