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1.
Cell ; 185(6): 949-966.e19, 2022 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-35247329

RESUMO

Beige fat plays key roles in the regulation of systemic energy homeostasis; however, detailed mechanisms and safe strategy for its activation remain elusive. In this study, we discovered that local hyperthermia therapy (LHT) targeting beige fat promoted its activation in humans and mice. LHT achieved using a hydrogel-based photothermal therapy activated beige fat, preventing and treating obesity in mice without adverse effects. HSF1 is required for the effects since HSF1 deficiency blunted the metabolic benefits of LHT. HSF1 regulates Hnrnpa2b1 (A2b1) transcription, leading to increased mRNA stability of key metabolic genes. Importantly, analysis of human association studies followed by functional analysis revealed that the HSF1 gain-of-function variant p.P365T is associated with improved metabolic performance in humans and increased A2b1 transcription in mice and cells. Overall, we demonstrate that LHT offers a promising strategy against obesity by inducing beige fat activation via HSF1-A2B1 transcriptional axis.


Assuntos
Tecido Adiposo Bege , Tecido Adiposo Branco , Hipertermia Induzida , Obesidade/terapia , Tecido Adiposo Bege/metabolismo , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo
2.
PLoS Genet ; 18(1): e1009968, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34986146

RESUMO

Taxane-induced peripheral neuropathy (TIPN) is a devastating survivorship issue for many cancer patients. In addition to its impact on quality of life, this toxicity may lead to dose reductions or treatment discontinuation, adversely impacting survival outcomes and leading to health disparities in African Americans (AA). Our lab has previously identified deleterious mutations in SET-Binding Factor 2 (SBF2) that significantly associated with severe TIPN in AA patients. Here, we demonstrate the impact of SBF2 on taxane-induced neuronal damage using an ex vivo model of SBF2 knockdown of induced pluripotent stem cell-derived sensory neurons. Knockdown of SBF2 exacerbated paclitaxel changes to cell viability and neurite outgrowth while attenuating paclitaxel-induced sodium current inhibition. Our studies identified paclitaxel-induced expression changes specific to mature sensory neurons and revealed candidate genes involved in the exacerbation of paclitaxel-induced phenotypes accompanying SBF2 knockdown. Overall, these findings provide ex vivo support for the impact of SBF2 on the development of TIPN and shed light on the potential pathways involved.


Assuntos
Paclitaxel/efeitos adversos , Doenças do Sistema Nervoso Periférico/genética , Polimorfismo de Nucleotídeo Único , Proteínas Tirosina Fosfatases não Receptoras/genética , Células Receptoras Sensoriais/citologia , Negro ou Afro-Americano/genética , Sobrevivência Celular/efeitos dos fármacos , Progressão da Doença , Feminino , Técnicas de Silenciamento de Genes , Humanos , Células-Tronco Pluripotentes Induzidas/química , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Paclitaxel/farmacologia , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/etnologia , Qualidade de Vida , Células Receptoras Sensoriais/química , Células Receptoras Sensoriais/efeitos dos fármacos , Análise de Sequência de RNA , Análise de Célula Única , População Branca/genética
3.
Br J Cancer ; 130(8): 1348-1355, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38347093

RESUMO

BACKGROUND: Bevacizumab is a beneficial therapy in several advanced cancer types. Predictive biomarkers to better understand which patients are destined to benefit or experience toxicity are needed. Associations between bevacizumab induced hypertension and survival have been reported but with conflicting conclusions. METHODS: We performed post-hoc analyses to evaluate the association in 3124 patients from two phase III adjuvant breast cancer trials, E5103 and BEATRICE. Differences in invasive disease-free survival (IDFS) and overall survival (OS) between patients with hypertension and those without were compared. Hypertension was defined as systolic blood pressure (SBP) ≥ 160 mmHg (n = 346) and SBP ≥ 180 mmHg (hypertensive crisis) (n = 69). Genomic analyses were performed to evaluate germline genetic predictors for the hypertensive crisis. RESULTS: Hypertensive crisis was significantly associated with superior IDFS (p = 0.015) and OS (p = 0.042), but only IDFS (p = 0.029; HR = 0.28) remained significant after correction for prognostic factors. SBP ≥ 160 mmHg was not associated with either IDFS or OS. A common single-nucleotide polymorphism, rs6486785, was significantly associated with hypertensive crisis (p = 8.4 × 10-9; OR = 5.2). CONCLUSION: Bevacizumab-induced hypertensive crisis is associated with superior outcomes and rs6486785 predicted an increased risk of this key toxicity.


Assuntos
Neoplasias da Mama , Hipertensão , Crise Hipertensiva , Feminino , Humanos , Bevacizumab/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/induzido quimicamente , Células Germinativas , Hipertensão/induzido quimicamente
4.
Phys Chem Chem Phys ; 26(12): 9517-9523, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38450673

RESUMO

3,4-Bis(3-nitrofurazan-4-yl)furoxan (DNTF) is a novel energetic material with an excellent performance and has attracted considerable attention. Motivated by recent theories and experiments, we had carried out experimental and theoretical studies on the high-pressure responses of vibrational characteristics, in conjunction with structural and electronic characteristics. It is found that all observed infrared spectra peaks seem to shift towards higher frequencies. And the peaks attributed to N-Oc (coordinated oxygen atom) stretching vibrations become broader due to the decrease of lattice constants and the free region of DNTF crystals with the increase of pressure, where the a-direction is more sensitive to pressure. In addition, the non-covalent interaction between adjacent DNTF molecules in the same layer changes from the van der Waals interaction to the steric effect with the increase of pressure, and that between layers also changes from the van der Waals interaction to the π-π stacking interaction. More importantly, these results highlight that the increase of pressure may lead to the stability decrease and impact the sensitivity increase of DNTF. This study can deepen the understanding of the energetic material DNTF under high pressure and is of great significance for blasting and detonation applications of DNTF.

5.
Nature ; 557(7703): 43-49, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29695866

RESUMO

Here we analyse genetic variation, population structure and diversity among 3,010 diverse Asian cultivated rice (Oryza sativa L.) genomes from the 3,000 Rice Genomes Project. Our results are consistent with the five major groups previously recognized, but also suggest several unreported subpopulations that correlate with geographic location. We identified 29 million single nucleotide polymorphisms, 2.4 million small indels and over 90,000 structural variations that contribute to within- and between-population variation. Using pan-genome analyses, we identified more than 10,000 novel full-length protein-coding genes and a high number of presence-absence variations. The complex patterns of introgression observed in domestication genes are consistent with multiple independent rice domestication events. The public availability of data from the 3,000 Rice Genomes Project provides a resource for rice genomics research and breeding.


Assuntos
Produtos Agrícolas/classificação , Produtos Agrícolas/genética , Variação Genética , Genoma de Planta/genética , Oryza/classificação , Oryza/genética , Ásia , Evolução Molecular , Genes de Plantas/genética , Genética Populacional , Genômica , Haplótipos , Mutação INDEL/genética , Filogenia , Melhoramento Vegetal , Polimorfismo de Nucleotídeo Único/genética
6.
Cereb Cortex ; 33(10): 6354-6365, 2023 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-36627243

RESUMO

Generalized anxiety disorder (GAD) is a common anxiety disorder experiencing psychological and somatic symptoms. Here, we explored the link between the individual variation in functional connectome and anxiety symptoms, especially psychological and somatic dimensions, which remains unknown. In a sample of 118 GAD patients and matched 85 healthy controls (HCs), we used multivariate distance-based matrix regression to examine the relationship between resting-state functional connectivity (FC) and the severity of anxiety. We identified multiple hub regions belonging to salience network (SN) and default mode network (DMN) where dysconnectivity associated with anxiety symptoms (P < 0.05, false discovery rate [FDR]-corrected). Follow-up analyses revealed that patient's psychological anxiety was dominated by the hyper-connectivity within DMN, whereas the somatic anxiety could be modulated by hyper-connectivity within SN and DMN. Moreover, hypo-connectivity between SN and DMN were related to both anxiety dimensions. Furthermore, GAD patients showed significant network-level FC changes compared with HCs (P < 0.01, FDR-corrected). Finally, we found the connectivity of DMN could predict the individual psychological symptom in an independent GAD sample. Together, our work emphasizes the potential dissociable roles of SN and DMN in the pathophysiology of GAD's anxiety symptoms, which may be crucial in providing a promising neuroimaging biomarker for novel personalized treatment strategies.


Assuntos
Conectoma , Humanos , Conectoma/métodos , Rede de Modo Padrão , Imageamento por Ressonância Magnética/métodos , Transtornos de Ansiedade/diagnóstico por imagem , Encéfalo/diagnóstico por imagem
7.
Lung ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958717

RESUMO

OBJECTIVES: This study was performed to construct and validate a risk prediction model for non-invasive ventilation (NIV) failure after birth in premature infants with gestational age < 32 weeks. METHODS: The data were derived from the multicenter retrospective study program - Jiangsu Provincial Neonatal Respiratory Failure Collaboration Network from Jan 2019 to Dec 2021. The subjects finally included were preterm infants using NIV after birth with gestational age less than 32 weeks and admission age within 72 h. After screening by inclusion and exclusion criteria, 1436 babies were subsequently recruited in the study, including 1235 infants in the successful NIV group and 201 infants in the failed NIV group. RESULTS: (1) Gestational age, 5 min Apgar, Max FiO2 during NIV, and FiO2 fluctuation value during NIV were selected by univariate and multivariate analysis. (2) The area under the curve of the prediction model was 0.807 (95% CI: 0.767-0.847) in the training set and 0.825 (95% CI: 0.766-0.883) in the test set. The calibration curve showed good agreement between the predicted probability and the actual observed probability (Mean absolute error = 0.008 for the training set; Mean absolute error = 0.012 for the test set). Decision curve analysis showed good clinical validity of the risk model in the training and test cohorts. CONCLUSION: This model performed well on dimensions of discrimination, calibration, and clinical validity. This model can serve as a useful tool for neonatologists to predict whether premature infants will experience NIV failure after birth.

8.
Health Commun ; : 1-16, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38655579

RESUMO

The role of experts in news coverage has become increasingly prominent, but the evidence regarding the effectiveness of expert opinions in affecting public behavior remains mixed. This study seeks to examine the influence of expert opinions covered in the news on the public's response to public health crises. By adopting a macro-level framing perspective, we investigated how framing consistency, a macro-level concept indicating the agreement between expert opinions in news coverage and government policies or among peer experts, evolves over time and its temporal causal relationship with public behavior. Specifically, this study collected all press news coverage in Hong Kong over four months during the fifth outbreak, including 1,416 articles with 650 expert opinions, as well as the vaccination data that paralleled with this period. We constructed time series of expert opinions and vaccination behavior, and then conducted Vector Autoregressive (VAR) models with Granger causality analysis to examine how framing consistency of expert opinions in news coverage influenced vaccination. The results indicate that the consistent framing between expert opinions and government policies increased COVID-19 vaccination during the fifth outbreak in Hong Kong, while conflicting opinions responding to government policies had no significant effect on vaccination. Opinions among medical experts on COVID-19 issues also did not significantly impact vaccination. The implications for designing communication strategies and enhancing public behavioral support during public health crises are discussed.

9.
Parasitol Res ; 123(2): 137, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38376760

RESUMO

Pangolins are susceptible to a variety of gastrointestinal nematodes due to their burrowing lifestyle and feeding habits, and few parasitic nematodes have been reported. Here, a Chinese pangolin with old wounds on its leg and tail was rescued from the Heyuan City, Guangdong Province. The cox1 and SSU rRNA of the worms from the intestine of the Chinese pangolin had the highest sequence identity of 89.58% and 97.95% to the species in the infraorder Spiruromorpha. The complete mitogenome of the worm was further assembled by next-generation sequencing, with a size of 13,708 bp and a GC content of 25.6%. The worm mitogenome had the highest sequence identity of 78.56% to that of Spirocerca lupi, sharing the same gene arrangement with S. lupi and some species in other families under Spiruromorpha. However, the mitogenome between the worm and S. lupi showed differences in codon usage of PCGs, sequences of NCR, and tRNA secondary structures. Phylogenetic analysis showed that the worm mitogenome was clustered with S. lupi in the family Thelaziidae to form a separate branch. However, it is still difficult to identify the worm in the family Thelaziidae because the species in the family Thelaziidae are confused, specifically S. lupi and Thelazia callipaeda in the family Thelaziidae were separated and grouped with species from other families. Thus, the parasitic nematode from the Chinese pangolin may be a novel species in Spiruromorpha and closely related to S. lupi. This study enriches the data on gastrointestinal nematodes in the Chinese pangolin.


Assuntos
Genoma Mitocondrial , Espirurídios , Thelazioidea , Humanos , Animais , Pangolins , Filogenia , Sequenciamento de Nucleotídeos em Larga Escala
10.
Adv Neonatal Care ; 24(1): 27-34, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38113903

RESUMO

BACKGROUND: There have been few reports on whether family integrated care (FIC) can help premature infants with moderate to severe bronchopulmonary dysplasia (BPD) to shorten the duration of home oxygen therapy (HOT). PURPOSE: To investigate the effect of FIC on the duration of HOT in premature infants with moderate to severe BPD. METHODS: The subjects were retrospectively selected from premature infants with moderate to severe BPD in our center between June 2019 and December 2021. Patients were divided into the FIC group (n = 47) and the non-FIC group (n = 34). For univariate analysis, t test, Mann-Whitney U test, Pearson χ 2 test, or Fisher exact test was performed to explore the differences between the 2 groups. For multivariate analysis, simple and multiple linear regression was conducted to explore the effect of FIC on the duration of HOT. RESULTS: (1) The duration of HOT and length of stay after grouping were significantly shorter in the FIC group than in the non-FIC group ( P < .05). (2) The results of linear regression further revealed that FIC could significantly shorten the duration of HOT (simple linear regression, FIC [A] B : -12.709, 95% confidence interval (CI): -21.665 to -3.753; multiple linear regression, FIC [B] B : -11.419, 95% CI: -18.055 to -4.783). IMPLICATIONS FOR PRACTICE AND RESEARCH: FIC improved the optimal target oxygen saturation ratio before discharge and shortened the duration of HOT in premature infants with moderate and severe BPD. FIC should be promoted in China's neonatal intensive care units, though it puts forward new requirements for nursing education and training.


Assuntos
Displasia Broncopulmonar , Prestação Integrada de Cuidados de Saúde , Recém-Nascido , Lactente , Humanos , Displasia Broncopulmonar/terapia , Estudos Retrospectivos , Recém-Nascido Prematuro , Oxigênio/uso terapêutico
11.
BMC Biol ; 21(1): 68, 2023 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-37013569

RESUMO

BACKGROUND: The accumulation of fatty acids in plants covers a wide range of functions in plant physiology and thereby affects adaptations and characteristics of species. As the famous woody oilseed crop, Acer truncatum accumulates unsaturated fatty acids and could serve as the model to understand the regulation and trait formation in oil-accumulation crops. Here, we performed Ribosome footprint profiling combing with a multi-omics strategy towards vital time points during seed development, and finally constructed systematic profiling from transcription to proteomes. Additionally, we characterized the small open reading frames (ORFs) and revealed that the translational efficiencies of focused genes were highly influenced by their sequence features. RESULTS: The comprehensive multi-omics analysis of lipid metabolism was conducted in A. truncatum. We applied the Ribo-seq and RNA-seq techniques, and the analyses of transcriptional and translational profiles of seeds collected at 85 and 115 DAF were compared. Key members of biosynthesis-related structural genes (LACS, FAD2, FAD3, and KCS) were characterized fully. More meaningfully, the regulators (MYB, ABI, bZIP, and Dof) were identified and revealed to affect lipid biosynthesis via post-translational regulations. The translational features results showed that translation efficiency tended to be lower for the genes with a translated uORF than for the genes with a non-translated uORF. They provide new insights into the global mechanisms underlying the developmental regulation of lipid metabolism. CONCLUSIONS: We performed Ribosome footprint profiling combing with a multi-omics strategy in A. truncatum seed development, which provides an example of the use of Ribosome footprint profiling in deciphering the complex regulation network and will be useful for elucidating the metabolism of A. truncatum seed oil and the regulatory mechanisms.


Assuntos
Acer , Ácidos Graxos , Ácidos Graxos/metabolismo , Transcriptoma , Perfilação da Expressão Gênica , Acer/genética , Acer/metabolismo , Ribossomos/metabolismo , Sementes/genética , Regulação da Expressão Gênica de Plantas
12.
Sensors (Basel) ; 24(7)2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38610454

RESUMO

In recent years, smartphones have emerged as the primary terminal for navigation and location services among mass users, owing to their universality, portability, and affordability. However, the highly integrated antenna design within smartphones inevitably introduces interference from internal signal sources, leading to a misalignment between the antenna phase center (APC) and the antenna geometric center. Accurately determining a smartphone's APC can mitigate system errors and enhance positioning accuracy, thereby meeting the increasing demand for precise and reliable user positioning. This paper delves into a detailed analysis of the generation of Global Navigation Satellite System (GNSS) receiver antenna phase center errors and proposes a method for correcting the receiver antenna phase center. Subsequently, a smartphone positioning experiment was conducted by placing the smartphone on an observation column with known coordinates. The collected observations were processed in static relative positioning mode, referencing observations from geodetic-grade equipment, and the accuracy of the static relative positioning fixed solution was evaluated. Following weighted estimation, we determined the antenna phase center of the Xiaomi Mi8 and corrected the APC. A comparison of the positioning results of the Xiaomi Mi8 before and after APC correction revealed minimal impact on the standard deviations (STDs) but significant influence on the root mean square errors (RMSEs). Specifically, the RMSEs in the E/N/U direction were reduced by 59.6%, 58.5%, and 42.0%, respectively, after APC correction compared to before correction. Furthermore, the integer ambiguity fixing rate slightly improved after the APC correction. In conclusion, the determination of a smartphone's APC can effectively reduce system errors in the plane direction of GNSS positioning, thereby enhancing smartphone positioning accuracy. This research holds significant value for advancing high-precision positioning studies related to smartphones.

13.
Mol Biol Evol ; 39(11)2022 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-36223453

RESUMO

MicroRNAs (miRNAs) are fast evolving endogenous small RNAs that regulate organism function and behavior in both animals and plants. Although models for de novo miRNA biogenesis have been proposed, the genomic mechanisms driving swift diversification of the miRNA repertoires in plants remain elusive. Here, by comprehensively analyzing 21 phylogenetically representative plant species, ranging from green algae to angiosperms, we systematically identified de novo miRNA events associated with 8,649 miRNA loci. We found that 399 (4.6%), 466 (5.4%), and 1,402 (16.2%) miRNAs were derived from inverted gene duplication events, long terminal repeats of retrotransposons, and miniature inverted-repeat transposable elements (MITEs), respectively. Among the miRNAs of these origins, MITEs, especially those belonging to the Mutator, Tc1/Mariner, and PIF/Harbinger superfamilies, were the predominant genomic source for de novo miRNAs in the 15 examined angiosperms but not in the six non-angiosperms. Our data further illustrated a transposition-transcription process by which MITEs are converted into new miRNAs (termed MITE-miRNAs) whereby properly sized MITEs are transcribed and therefore become potential substrates for the miRNA processing machinery by transposing into introns of active genes. By analyzing the 58,038 putative target genes for the 8,095 miRNAs, we found that the target genes of MITE-miRNAs were preferentially associated with response to environmental stimuli such as temperature, suggesting that MITE-miRNAs are pertinent to plant adaptation. Collectively, these findings demonstrate that molecular conversion of MITEs is a genomic mechanism leading to rapid and continuous changes to the miRNA repertoires in angiosperm.


Assuntos
Magnoliopsida , MicroRNAs , Animais , MicroRNAs/genética , Elementos de DNA Transponíveis/genética , Magnoliopsida/genética , Duplicação Gênica , Retroelementos , Plantas/genética , Sequências Repetidas Invertidas
14.
New Phytol ; 238(3): 1245-1262, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36751914

RESUMO

Fructans in angiosperms play essential roles in physiological functions and environmental adaptations. As a major source of industrial fructans (especially inulin-type), chicory (Cichorium intybus L.) is a model species for studying fructan biosynthesis. However, the genes underlying this process and their evolutionary history in angiosperms remain elusive. We combined multiple sequencing technologies to assemble and annotate the chicory genome and scan its (epi)genomic features, such as genomic components, DNA methylation, and three-dimensional (3D) structure. We also performed a comparative genomics analysis to uncover the associations between key traits and gene families. We achieved a nearly complete chicory genome assembly and found that continuous bursts of a few highly active retrotransposon families largely shaped the (epi)genomic characteristics. The highly methylated genome with its unique 3D structure potentially influences critical biological processes. Our comprehensive comparative genomics analysis deciphered the genetic basis for the rich sesquiterpene content in chicory and indicated that the fructan-accumulating trait resulted from convergent evolution in angiosperms due to shifts in critical sites of fructan-active enzymes. The highly characterized chicory genome provides insight into Asteraceae evolution and fructan biosynthesis in angiosperms.


Assuntos
Cichorium intybus , Frutanos , Magnoliopsida , Asteraceae/genética , Metabolismo dos Carboidratos , Cichorium intybus/genética , Frutanos/biossíntese , Magnoliopsida/genética
15.
Cancer Cell Int ; 23(1): 204, 2023 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-37716943

RESUMO

BACKGROUND: Triple negative breast cancer (TNBC) represents a significant clinical challenge. Chemotherapy remains the mainstay for a large part of TNBC patients, whereas drug resistance and tumor recurrence frequently occur. It is in urgent need to identify novel molecular targets for TNBC and develop effective therapy against the aggressive disease. METHODS: Immunohistochemistry was performed to examine the expression of HER3 in TNBC samples. Western blots were used to assess protein expression and activation. Cell proliferation and viability were determined by cell growth (MTS) assays. TCGA databases were analyzed to correlate HER3 mRNA expression with the clinical outcomes of TNBC patients. Specific shRNA was used to knockdown HER3 expression. IncuCyte system was utilized to monitor cell growth and migration. LIVE/DEAD Cell Imaging was to detect live and dead cells. HER3 recognition by our anti-HER3 monoclonal antibody (mAb) 4A7 was verified by ELISA, flow cytometry, and co-immunoprecipitation assays. Orthotopic tumor models were established in nude mice to determine the capability of TNBC cells forming tumors and to test if our mAb 4A7 could potentiate the antitumor activity of paclitaxel in vivo. RESULTS: Elevated expression of HER3 was observed in approximately half of the TNBC specimens and cell lines tested. Analyses of TCGA databases found that the TNBC patients with high HER3 mRNA expression in the tumors showed significantly worse overall survival (OS) and relapse-free survival (RFS) than those with low HER3 expression. Specific knockdown of HER3 markedly inhibited TNBC cell proliferation and mammosphere formation in vitro and tumor growth in vivo. Our mAb 4A7 abrogated heregulin (a ligand for HER3), but not SDF-1 (a ligand for CXCR4)-induced enhancement of TNBC cell migration. Combinations of 4A7 and the EGFR-tyrosine kinase inhibitor (TKI) gefitinib dramatically decreased the levels of phosphorylated HER3, EGFR, Akt, and ERK1/2 in TNBC cells and potently induced growth inhibition and cell death. Moreover, 4A7 in combination with paclitaxel exerted significant antitumor activity against TNBC in vitro and in vivo. CONCLUSIONS: Our data demonstrate that increased HER3 is an effective therapeutic target for TNBC and our anti-HER3 mAb (4A7) may enhance the efficacy of gefitinib or paclitaxel in TNBC.

16.
BMC Infect Dis ; 23(1): 373, 2023 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-37270474

RESUMO

BACKGROUND: Individuals in close contact with active pulmonary tuberculosis (TB) patients showed a high risk of recent infection and, once infected, higher risk of developing active TB in the following years post-exposure. But the peak time of active disease onset is unclear. This study aims to estimate post exposure TB incidence risk among close contacts to provide reference for clinical and public health strategies. METHODS: We searched PubMed, Web of Science, and EMBASE for articles published until December 1, 2022. The incidence rates were quantitatively summarized by means of meta-analysis using the random-effect model. RESULTS: Of the 5616 studies, 31 studies included in our analysis. For baseline close contacts results, the summarized prevalence of Mycobacterium tuberculosis (MTB) infection and active TB was found to be 46.30% (95% CI: 37.18%-55.41%) and 2.68% (95% CI: 2.02%-3.35%), respectively. During the follow-up, the 1-year, 2-year and 5-year cumulative incidence of TB in close contacts were 2.15% (95% CI: 1.51%-2.80%), 1.21% (95% CI: 0.93%-1.49%) and 1.11% (95% CI: 0.64%-1.58%), respectively. Individuals with a positive result of MTB infection testing at baseline showed significantly higher cumulative TB incidence as compared to those negatives (3.80% vs. 0.82%, p < 0.001). CONCLUSIONS: Individuals with close contact to active pulmonary TB patients are bearing significant risk of developing active TB, particularly within the first-year post-exposure. Population with recent infections should be an important priority for active case finding and preventive intervention worldwide.


Assuntos
Mycobacterium tuberculosis , Tuberculose Pulmonar , Tuberculose , Humanos , Incidência , Busca de Comunicante/métodos , Tuberculose/epidemiologia , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/prevenção & controle
17.
Environ Sci Technol ; 57(27): 10117-10126, 2023 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-37364020

RESUMO

Electrocatalytic reduction of nitrate to NH3 (NO3RR) on Cu offers sustainable NH3 production and nitrogen recycling from nitrate-contaminated water. However, Cu affords limited NO3RR activity owing to its unfavorable electronic state and the slow proton transfer on its surface, especially in neutral/alkaline media. Furthermore, although a synchronous "NO3RR and NH3 collection" system has been developed for nitrogen recycling from nitrate-laden water, no system is designed for natural water that generally contains low-concentration nitrate. Herein, we demonstrate that depositing Cu nanoparticles on a TiO2 support enables the formation of electron-deficient Cuδ+ species (0 < δ ≤ 2), which are more active than Cu0 in NO3RR. Furthermore, TiO2-Cu coupling induces local electric-field enhancement that intensifies water adsorption/dissociation at the interface, accelerating proton transfer for NO3RR on Cu. With the dual enhancements, TiO2-Cu delivers an NH3-N selectivity of 90.5%, mass activity of 41.4 mg-N h gCu-1, specific activity of 377.8 mg-N h-1 m-2, and minimal Cu leaching (<25.4 µg L-1) when treating 22.5 mg L-1 of NO3--N at -0.40 V, outperforming most of the reported Cu-based catalysts. A sequential NO3RR and NH3 collection system based on TiO2-Cu was then proposed, which could recycle nitrogen from nitrate-contaminated water under a wide concentration window of 22.5-112.5 mg L-1 at a rate of 209-630 mgN m-2 h-1. We also demonstrated this system could collect 83.9% of nitrogen from NO3--N (19.3 mg L-1) in natural lake water.


Assuntos
Nanopartículas , Nitratos , Nitratos/química , Prótons , Cobre , Nitrogênio , Água
18.
Eur J Nutr ; 62(2): 771-782, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36261730

RESUMO

PURPOSE: Fruit intake is beneficial to several chronic diseases, but controversial in diabetes. We aimed to investigate prospectively the associations of whole fresh fruit intake with risk of incident type 2 diabetes (T2D) in subjects with different glucose regulation capacities. METHODS: The present study included 79,922 non-diabetic participants aged ≥ 40 years from an ongoing nationwide prospective cohort in China. Baseline fruit intake information was collected by a validated food frequency questionnaire. Plasma HbA1c, fasting and 2 h post-loading glucose levels were measured at both baseline and follow-up examinations. Cox proportional hazards models were used to calculate hazard ratio (HR) and 95% confidence intervals (CI) for incident diabetes among participants with normal glucose tolerance (NGT) and prediabetes, after adjusted for multiple confounders. Restricted cubic spline analysis was applied for dose-response relation. RESULTS: During a median 3.8-year follow-up, 5886 (7.36%) participants developed diabetes. Overall, we identified a linear and dose-dependent inverse association between dietary whole fresh fruit intake and risk of incident T2D. Each 100 g/d higher fruit intake was associated with 2.8% lower risk of diabetes (HR 0.972, 95%CI [0.949-0.996], P = 0.0217), majorly benefiting NGT subjects with 15.2% lower risk (HR 0.848, 95%CI [0.766-0.940], P = 0.0017), while not significant in prediabetes (HR 0.981, 95%CI 0.957-4.005, P = 0.1268). Similarly, the inverse association was present in normoglycemia individuals with a 48.6% lower risk of diabetes when consuming fruits > 7 times/week comparing to those < 1 time/week (HR 0.514, 95% CI [0.368-0.948]), but not in prediabetes (HR 0.883, 95% CI [0.762-1.023]). CONCLUSION: These findings suggest that higher frequency and amount of fresh fruit intake may protect against incident T2D, especially in NGT, but not in prediabetes, highlighting the dietary recommendation of higher fresh fruit consumption to prevent T2D in normoglycemia population.


Assuntos
Diabetes Mellitus Tipo 2 , Estado Pré-Diabético , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Frutas , Estudos Prospectivos , Incidência , Glucose , Fatores de Risco
19.
Ecotoxicol Environ Saf ; 251: 114521, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36641864

RESUMO

Microplastics (MPs) has shown adsorption of hydrophilic organic matters (HOMs) in aqueous environments. However, it is still difficult to predict the adsorption behaviors of HOMs by different MPs, especially in authentic water systems. In this study, the adsorption behaviors and mechanisms of norfloxacin (NOR) onto polyamide (PA) MPs were investigated in both simulated and real surface water. The results showed that the adsorption equilibrium of NOR by PA in simulated surface water could be achieved within 15 h, while the adsorption rate of NOR in real surface was slowed down, with the equilibrium time of 25 h. Pseudo-second-order model could well describe the adsorption kinetics data. The experimental maximum adsorption capacity of NOR on PA in real surface water (e. g. 132.54 ug/g) was dramatically reduced by 37.5 % compared with that in simulated surface water (e. g. 212.25 ug/g), and the adsorption isotherm would obey Freundlich model. Besides, the leaching of NOR from the surface of PA could occur obviously at acidic environment. Furthermore, the salinity and natural organic matter exhibited significantly adverse effects on the NOR adsorption. Finally, the results of 2D Fourier transform infrared correlation spectroscopy and X-ray photoelectron spectroscopy indicated that the electrostatic, H-bond and van der Waals interactions were involved in the adsorption. More importantly, the sequential functional groups in the adsorption process followed the orders: 1638 (CO) > 1542 amide II (-NH-CO) > 717 (CH2) > 1445 (CO) > 973 amide IV (CONH). This study could provide an insight into the interactions between PA and NOR in different water environments.


Assuntos
Poluentes Químicos da Água , Água , Microplásticos , Norfloxacino , Plásticos/química , Espectroscopia de Infravermelho com Transformada de Fourier , Espectroscopia Fotoeletrônica , Poluentes Químicos da Água/análise , Concentração de Íons de Hidrogênio , Nylons , Adsorção , Cinética
20.
Ecotoxicol Environ Saf ; 263: 115366, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37573610

RESUMO

Advanced oxidation processes (AOPs) based on ultrasound (US) have attracted considerable attention in recent years due to its advantages in the degradation of landfill leachate. The review summarizes the existing treatment methods of leachate from lab-scale, compares their advantages and disadvantages by focusing on the degradation of emerging contaminants (ECs) in the leachate. Then the US-based AOPs are introduced emphatically, including their degradation mechanisms, influencing factors, energy consumption, further optimization methods as well as the possibility of field-scale application are systematically described. Moreover, this review also expounds on the advantages of dual-frequency US (DFUS) technology compared with single-frequency US, and a theoretically feasible DFUS process is proposed to treat ECs in the leachate. Finally, suggestions and prospects for US technologies in treating landfill leachate are put forward to aid future research on landfill leachate treatment. Meaningfully, this manuscript will provide reference values of US-based technologies in landfill leachate treatment for the practical use, facilitating the development of US-based AOPs in landfill leachate management and disposal.


Assuntos
Poluentes Químicos da Água , Oxirredução
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