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1.
Nature ; 614(7946): 81-87, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36725999

RESUMO

Micro-LEDs (µLEDs) have been explored for augmented and virtual reality display applications that require extremely high pixels per inch and luminance1,2. However, conventional manufacturing processes based on the lateral assembly of red, green and blue (RGB) µLEDs have limitations in enhancing pixel density3-6. Recent demonstrations of vertical µLED displays have attempted to address this issue by stacking freestanding RGB LED membranes and fabricating top-down7-14, but minimization of the lateral dimensions of stacked µLEDs has been difficult. Here we report full-colour, vertically stacked µLEDs that achieve, to our knowledge, the highest array density (5,100 pixels per inch) and the smallest size (4 µm) reported to date. This is enabled by a two-dimensional materials-based layer transfer technique15-18 that allows the growth of RGB LEDs of near-submicron thickness on two-dimensional material-coated substrates via remote or van der Waals epitaxy, mechanical release and stacking of LEDs, followed by top-down fabrication. The smallest-ever stack height of around 9 µm is the key enabler for record high µLED array density. We also demonstrate vertical integration of blue µLEDs with silicon membrane transistors for active matrix operation. These results establish routes to creating full-colour µLED displays for augmented and virtual reality, while also offering a generalizable platform for broader classes of three-dimensional integrated devices.

2.
Proc Natl Acad Sci U S A ; 121(14): e2314231121, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38527197

RESUMO

Despite experimental and observational studies demonstrating that biodiversity enhances primary productivity, the best metric for predicting productivity at broad geographic extents-functional trait diversity, phylogenetic diversity, or species richness-remains unknown. Using >1.8 million tree measurements from across eastern US forests, we quantified relationships among functional trait diversity, phylogenetic diversity, species richness, and productivity. Surprisingly, functional trait and phylogenetic diversity explained little variation in productivity that could not be explained by tree species richness. This result was consistent across the entire eastern United States, within ecoprovinces, and within data subsets that controlled for biomass or stand age. Metrics of functional trait and phylogenetic diversity that were independent of species richness were negatively correlated with productivity. This last result suggests that processes that determine species sorting and packing are likely important for the relationships between productivity and biodiversity. This result also demonstrates the potential confusion that can arise when interdependencies among different diversity metrics are ignored. Our findings show the value of species richness as a predictive tool and highlight gaps in knowledge about linkages between functional diversity and ecosystem functioning.


Assuntos
Biodiversidade , Florestas , Biomassa , Ecossistema , Filogenia , Estados Unidos
3.
Lancet ; 404(10457): 1040-1050, 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39236727

RESUMO

BACKGROUND: The long-term impact of drug-coated balloon (DCB) angioplasty for the treatment of patients with de novo coronary artery lesions remains uncertain. We aimed to assess the non-inferiority of DCB angioplasty with rescue stenting to intended drug-eluting stent (DES) deployment for patients with de novo, non-complex coronary artery lesions. METHODS: REC-CAGEFREE I was an open-label, randomised, non-inferiority trial conducted at 43 sites in China. After successful lesion pre-dilatation, patients aged 18 years or older with de novo, non-complex coronary artery disease (irrespective of target vessel diameter) and an indication for percutaneous coronary intervention were randomly assigned (1:1), via a web-based centralised system with block randomisation (block size of two, four, or six) and stratified by site, to paclitaxel-coated balloon angioplasty with the option of rescue stenting due to an unsatisfactory result (DCB group) or intended deployment of second-generation thin-strut sirolimus-eluting stents (DES group). The primary outcome was the device-oriented composite endpoint (DoCE; including cardiovascular death, target vessel myocardial infarction, and clinically and physiologically indicated target lesion revascularisation) assessed at 24 months in the intention-to-treat (ITT) population (ie, all participants randomly assigned to treatment). Non-inferiority was established if the upper limit of the one-sided 95% CI for the absolute risk difference was smaller than 2·68%. Safety was assessed in the ITT population. This study is registered with ClinicalTrials.gov, NCT04561739. It is closed to accrual and extended follow-up is ongoing. FINDINGS: Between Feb 5, 2021, and May 1, 2022, 2272 patients were randomly assigned to the DCB group (1133 [50%]) or the DES group (1139 [50%]). Median age at the time of randomisation was 62 years (IQR 54-69), 1574 (69·3%) of 2272 were male, 698 (30·7%) were female, and all patients were of Chinese ethnicity. 106 (9·4%) of 1133 patients in the DCB group received rescue DES after unsatisfactory DCB angioplasty. As of data cutoff (May 1, 2024), median follow-up was 734 days (IQR 731-739). At 24 months, the DoCE occurred in 72 (6·4%) of 1133 patients in the DCB group and 38 (3·4%) of 1139 in the DES group, with a risk difference of 3·04% in the cumulative event rate (upper boundary of the one-sided 95% CI 4·52; pnon-inferiority=0·65; two-sided 95% CI 1·27-4·81; p=0·0008); the criterion for non-inferiority was not met. During intervention, no acute vessel closures occurred in the DCB group and one (0·1%) of 1139 patients in the DES group had acute vessel closure. Periprocedural myocardial infarction occurred in ten (0·9%) of 1133 patients in the DCB group and nine (0·8%) in the DES group. INTERPRETATION: In patients with de novo, non-complex coronary artery disease, irrespective of vessel diameter, a strategy of DCB angioplasty with rescue stenting did not achieve non-inferiority compared with the intended DES implantation in terms of the DoCE at 2 years, which indicates that DES should remain the preferred treatment for this patient population. FUNDING: Xijing Hospital and Shenqi Medical. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.


Assuntos
Angioplastia Coronária com Balão , Doença da Artéria Coronariana , Stents Farmacológicos , Paclitaxel , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Angioplastia Coronária com Balão/métodos , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Doença da Artéria Coronariana/terapia , Idoso , Sirolimo/uso terapêutico , Sirolimo/administração & dosagem , Resultado do Tratamento , Materiais Revestidos Biocompatíveis , China/epidemiologia , Intervenção Coronária Percutânea/métodos
4.
J Virol ; 98(3): e0004224, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38376198

RESUMO

Influenza D virus (IDV) utilizes bovines as a primary reservoir with periodical spillover to other hosts. We have previously demonstrated that IDV binds both 9-O-acetylated N-acetylneuraminic acid (Neu5,9Ac2) and 9-O-acetylated N-glycolylneuraminic acid (Neu5Gc9Ac). Bovines produce both Neu5,9Ac2 and Neu5Gc9Ac, while humans are genetically unable to synthesize Neu5Gc9Ac. 9-O-Acetylation of sialic acids is catalyzed by CASD1 via a covalent acetyl-enzyme intermediate. To characterize the role of Neu5,9Ac2 and Neu5Gc9Ac in IDV infection and determine which form of 9-O-acetylated sialic acids drives IDV entry, we took advantage of a CASD1 knockout (KO) MDCK cell line and carried out feeding experiments using synthetic 9-O-acetyl sialic acids in combination with the single-round and multi-round IDV infection assays. The data from our studies show that (i) CASD1 KO cells are resistant to IDV infection and lack of IDV binding to the cell surface is responsible for the failure of IDV replication; (ii) feeding CASD1 KO cells with Neu5,9Ac2 or Neu5Gc9Ac resulted in a dose-dependent rescue of IDV infectivity; and (iii) diverse IDVs replicated robustly in CASD1 KO cells fed with either Neu5,9Ac2 or Neu5Gc9Ac at a level similar to that in wild-type cells with a functional CASD1. These data demonstrate that IDV can utilize Neu5,9Ac2- or non-human Neu5Gc9Ac-containing glycan receptor for infection. Our findings provide evidence that IDV has acquired the ability to infect and transmit among agricultural animals that are enriched in Neu5Gc9Ac, in addition to posing a zoonotic risk to humans expressing only Neu5,9Ac2.IMPORTANCEInfluenza D virus (IDV) has emerged as a multiple-species-infecting pathogen with bovines as a primary reservoir. Little is known about the functional receptor that drives IDV entry and promotes its cross-species spillover potential among different hosts. Here, we demonstrated that IDV binds exclusively to 9-O-acetylated N-acetylneuraminic acid (Neu5,9Ac2) and non-human 9-O-acetylated N-glycolylneuraminic acid (Neu5Gc9Ac) and utilizes both for entry and infection. This ability in effective engagement of both 9-O-acetylated sialic acids as functional receptors for infection provides an evolutionary advantage to IDV for expanding its host range. This finding also indicates that IDV has the potential to emerge in humans because Neu5,9Ac2 is ubiquitously expressed in human tissues, including lung. Thus, results of our study highlight a need for continued surveillance of IDV in humans, as well as for further investigation of its biology and cross-species transmission mechanism.


Assuntos
Deltainfluenzavirus , Ácidos Neuramínicos , Receptores Virais , Animais , Bovinos , Membrana Celular/metabolismo , Ácido N-Acetilneuramínico/metabolismo , Ácidos Neuramínicos/metabolismo , Orthomyxoviridae/metabolismo , Receptores Virais/metabolismo , Ácidos Siálicos/metabolismo
5.
Proc Natl Acad Sci U S A ; 119(29): e2201747119, 2022 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-35858353

RESUMO

Bacteria have evolved multiple signal transduction systems that permit an adaptation to changing environmental conditions. Chemoreceptor-based signaling cascades are very abundant in bacteria and are among the most complex signaling systems. Currently, our knowledge on the molecular features that determine signal recognition at chemoreceptors is limited. Chemoreceptor McpA of Bacillus velezensis SQR9 has been shown to mediate chemotaxis to a broad range of different ligands. Here we show that its ligand binding domain binds directly 13 chemoattractants. We provide support that organic acids and amino acids bind to the membrane-distal and membrane-proximal module of the dCache domain, respectively, whereas binding of sugars/sugar alcohols occurred at both modules. Structural biology studies combined with site-directed mutagenesis experiments have permitted to identify 10 amino acid residues that play key roles in the recognition of multiple ligands. Residues in membrane-distal and membrane-proximal regions were central for sensing organic acids and amimo acids, respectively, whereas all residues participated in sugars/sugar alcohol sensing. Most characterized chemoreceptors possess a narrow and well-defined ligand spectrum. We propose here a sensing mechanism involving both dCache modules that allows the integration of very diverse signals by a single chemoreceptor.


Assuntos
Bacillus , Proteínas de Bactérias , Quimiotaxia , Proteínas Quimiotáticas Aceptoras de Metil , Bacillus/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Ligantes , Proteínas Quimiotáticas Aceptoras de Metil/química , Proteínas Quimiotáticas Aceptoras de Metil/metabolismo , Ligação Proteica , Domínios Proteicos , Açúcares/química
6.
Genes Dev ; 31(10): 973-989, 2017 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-28607179

RESUMO

Developmental and lineage plasticity have been observed in numerous malignancies and have been correlated with tumor progression and drug resistance. However, little is known about the molecular mechanisms that enable such plasticity to occur. Here, we describe the function of the plant homeodomain finger protein 6 (PHF6) in leukemia and define its role in regulating chromatin accessibility to lineage-specific transcription factors. We show that loss of Phf6 in B-cell leukemia results in systematic changes in gene expression via alteration of the chromatin landscape at the transcriptional start sites of B-cell- and T-cell-specific factors. Additionally, Phf6KO cells show significant down-regulation of genes involved in the development and function of normal B cells, show up-regulation of genes involved in T-cell signaling, and give rise to mixed-lineage lymphoma in vivo. Engagement of divergent transcriptional programs results in phenotypic plasticity that leads to altered disease presentation in vivo, tolerance of aberrant oncogenic signaling, and differential sensitivity to frontline and targeted therapies. These findings suggest that active maintenance of a precise chromatin landscape is essential for sustaining proper leukemia cell identity and that loss of a single factor (PHF6) can cause focal changes in chromatin accessibility and nucleosome positioning that render cells susceptible to lineage transition.


Assuntos
Cromatina/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Leucemia de Células B/genética , Leucemia de Células B/fisiopatologia , Animais , Linhagem Celular Tumoral , Linhagem da Célula/genética , Cromatina/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Técnicas de Inativação de Genes , Linfoma não Hodgkin/genética , Camundongos , Camundongos Endogâmicos C57BL , Fenótipo , Proteínas Repressoras , Transdução de Sinais/genética
7.
J Cell Mol Med ; 28(14): e18521, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39021279

RESUMO

In the present study, the debatable prognostic value of Ki67 in patients with non-small cell lung cancer (NSCLC) was attributed to the heterogeneity between lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC). Based on meta-analyses of 29 studies, a retrospective immunohistochemical cohort of 1479 patients from our center, eight transcriptional datasets and a single-cell datasets with 40 patients, we found that high Ki67 expression suggests a poor outcome in LUAD, but conversely, low Ki67 expression indicates worse prognosis in LUSC. Furthermore, low proliferation in LUSC is associated with higher metastatic capacity, which is related to the stronger epithelial-mesenchymal transition potential, immunosuppressive microenvironment and angiogenesis. Finally, nomogram model incorporating clinical risk factors and Ki67 expression outperformed the basic clinical model for the accurate prognostic prediction of LUSC. With the largest prognostic assessment of Ki67 from protein to mRNA level, our study highlights that Ki67 also has an important prognostic value in NSCLC, but separate evaluation of LUAD and LUSC is necessary to provide more valuable information for clinical decision-making in NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Imuno-Histoquímica , Antígeno Ki-67 , Neoplasias Pulmonares , Humanos , Antígeno Ki-67/metabolismo , Antígeno Ki-67/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Prognóstico , Feminino , Masculino , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Pessoa de Meia-Idade , Idoso , Nomogramas , Microambiente Tumoral/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Transição Epitelial-Mesenquimal/genética , Estudos Retrospectivos
8.
BMC Genomics ; 25(1): 639, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926642

RESUMO

BACKGROUND: Aging is a prominent risk factor for diverse diseases; therefore, an in-depth understanding of its physiological mechanisms is required. Nonhuman primates, which share the closest genetic relationship with humans, serve as an ideal model for exploring the complex aging process. However, the potential of the nonhuman primate animal model in the screening of human aging markers is still not fully exploited. Multiomics analysis of nonhuman primate peripheral blood offers a promising approach to evaluate new therapies and biomarkers. This study explores aging-related biomarker through multilayer omics, including transcriptomics (mRNA, lncRNA, and circRNA) and proteomics (serum and serum-derived exosomes) in rhesus monkeys (Macaca mulatta). RESULTS: Our findings reveal that, unlike mRNAs and circRNAs, highly expressed lncRNAs are abundant during the key aging period and are associated with cancer pathways. Comparative analysis highlighted exosomal proteins contain more types of proteins than serum proteins, indicating that serum-derived exosomes primarily regulate aging through metabolic pathways. Finally, eight candidate aging biomarkers were identified, which may serve as blood-based indicators for detecting age-related brain changes. CONCLUSIONS: Our results provide a comprehensive understanding of nonhuman primate blood transcriptomes and proteomes, offering novel insights into the aging mechanisms for preventing or treating age-related diseases.


Assuntos
Envelhecimento , Biomarcadores , Exossomos , Macaca mulatta , Proteômica , Animais , Envelhecimento/genética , Biomarcadores/sangue , Exossomos/metabolismo , Exossomos/genética , Proteômica/métodos , Transcriptoma , Perfilação da Expressão Gênica , RNA Longo não Codificante/genética , RNA Longo não Codificante/sangue , RNA Longo não Codificante/metabolismo , Modelos Animais , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteoma/metabolismo , Genômica/métodos
9.
Small ; 20(34): e2312210, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38600878

RESUMO

Oxygen-vacancy (Ov) engineering is an effective strategy to manipulate the electronic configuration of catalysts for electrochemical nitrogen reduction reaction (eNRR). The influence of the stable facet on the electronic configuration of Ov is widely studied, however, the effect of the reactive facet on the local electron density of Ov is unveiled. In this work, an eNRR electrode R(111)-TiO2/HGO is provided with a high proportion exposed reactive facet (111) of rutile-TiO2 (denoted as R(111)-TiO2) nanocrystals with Ov anchored in hierarchically porous graphite oxide (HGO) nanofilms. The R(111)-TiO2/HGO exhibits excellent eNRR performance with an NH3 yield rate of 20.68 µg h-1 cm-2, which is ≈20 times the control electrode with the most stable facet (110) exposed (R(110)-TiO2/HGO). The experimental data and theoretical simulations reveal that the crystal facet (111) has a positive effect on regulating the local electron density around the oxygen vacancy and the two adjacent Ti-sites, promoting the π-back-donation, minimizing the eNRR barrier, and transforming the rate determination step to *NNH→*NNHH. This work illuminates the effect of crystal facet on the performance of eNRR, and offers a novel strategy to design efficient eNRR catalysts.

10.
Genes Cells ; 28(5): 348-363, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36811212

RESUMO

Colorectal cancer (CRC) is one of the leading malignant cancers. DNA damage response (DDR), referring to the molecular process of DNA damage, is emerging as a promising field in targeted cancer therapy. However, the engagement of DDR in the remodeling of the tumor microenvironment is rarely studied. In this study, by sequential nonnegative matrix factorization (NMF) algorithm, pseudotime analysis, cell-cell interaction analysis, and SCENIC analysis, we have shown that DDR genes demonstrate various patterns among different cell types in CRC TME (tumor microenvironment), especially in epithelial cells, cancer-associated fibroblasts, CD8+ T cells, tumor-associated macrophages, which enhance the intensity of intercellular communication and transcription factor activation. Furthermore, based on the newly identified DDR-related TME signatures, cell subtypes including MNAT+CD8+T_cells-C5, POLR2E+Mac-C10, HMGB2+Epi-C4, HMGB1+Mac-C11, PER1+Mac-C5, PER1+CD8+T_cells-C1, POLR2A+Mac-C1, TDG+Epi-C5, TDG+CD8+T_cells-C8 are determined as critical prognostic factors for CRC patients and predictors of immune checkpoint blockade (ICB) therapy efficacy in two public CRC cohorts, TCGA-COAD and GSE39582. Our novel and systematic analysis on the level of the single-cell analysis has revealed the unique role of DDR in remodeling CRC TME for the first time, facilitating the prediction of prognosis and guidance of personalized ICB regimens in CRC.


Assuntos
Neoplasias Colorretais , Microambiente Tumoral , Humanos , Microambiente Tumoral/genética , Imunoterapia , Algoritmos , Dano ao DNA/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia
11.
New Phytol ; 242(6): 2401-2410, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38494698

RESUMO

The rhizosphere microbiome plays critical roles in plant growth and provides promising solutions for sustainable agriculture. While the rhizosphere microbiome frequently fluctuates with the soil environment, recent studies have demonstrated that a small proportion of the microbiome is consistently assembled in the rhizosphere of a specific plant genotype regardless of the soil condition, which is determined by host genetics. Based on these breakthroughs, which involved exploiting the plant-beneficial function of the rhizosphere microbiome, we propose to divide the rhizosphere microbiome into environment-dominated and plant genetic-dominated components based on their different assembly mechanisms. Subsequently, two strategies to explore the different rhizosphere microbiome components for agricultural production are suggested, that is, the precise management of the environment-dominated rhizosphere microbiome by agronomic practices, and the elucidation of the plant genetic basis of the plant genetic-dominated rhizosphere microbiome for breeding microbiome-assisted crop varieties. We finally present the major challenges that need to be overcome to implement strategies for modulating these two components of the rhizosphere microbiome.


Assuntos
Agricultura , Microbiota , Rizosfera , Agricultura/métodos , Produtos Agrícolas/microbiologia , Desenvolvimento Sustentável , Microbiologia do Solo
12.
J Exp Bot ; 75(2): 526-537, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37419655

RESUMO

Every living organism on Earth depends on its interactions with other organisms. In the rhizosphere, plants and microorganisms constantly exchange signals and influence each other's behavior. Recent studies have shown that many beneficial rhizosphere microbes can produce specific signaling molecules that affect plant root architecture and therefore could have substantial effects on above-ground growth. This review examines these chemical signals and summarizes their mechanisms of action, with the aim of enhancing our understanding of plant-microbe interactions and providing references for the comprehensive development and utilization of these active components in agricultural production. In addition, we highlight future research directions and challenges, such as searching for microbial signals to induce primary root development.


Assuntos
Raízes de Plantas , Plantas , Agricultura , Raízes de Plantas/microbiologia , Rizosfera
13.
J Exp Bot ; 75(11): 3388-3400, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38497798

RESUMO

Nitrogen fertilizer is widely used in agriculture to boost crop yields. Plant growth-promoting rhizobacteria (PGPRs) can increase plant nitrogen use efficiency through nitrogen fixation and organic nitrogen mineralization. However, it is not known whether they can activate plant nitrogen uptake. In this study, we investigated the effects of volatile compounds (VCs) emitted by the PGPR strain Bacillus velezensis SQR9 on plant nitrogen uptake. Strain SQR9 VCs promoted nitrogen accumulation in both rice and Arabidopsis. In addition, isotope labeling experiments showed that strain SQR9 VCs promoted the absorption of nitrate and ammonium. Several key nitrogen-uptake genes were up-regulated by strain SQR9 VCs, such as AtNRT2.1 in Arabidopsis and OsNAR2.1, OsNRT2.3a, and OsAMT1 family members in rice, and the deletion of these genes compromised the promoting effect of strain SQR9 VCs on plant nitrogen absorption. Furthermore, calcium and the transcription factor NIN-LIKE PROTEIN 7 play an important role in nitrate uptake promoted by strain SQR9 VCs. Taken together, our results indicate that PGPRs can promote nitrogen uptake through regulating plant endogenous signaling and nitrogen transport pathways.


Assuntos
Arabidopsis , Bacillus , Nitrogênio , Oryza , Transdução de Sinais , Bacillus/metabolismo , Bacillus/fisiologia , Bacillus/genética , Nitrogênio/metabolismo , Oryza/microbiologia , Oryza/metabolismo , Oryza/genética , Arabidopsis/metabolismo , Arabidopsis/microbiologia , Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Compostos Orgânicos Voláteis/metabolismo
14.
BMC Cancer ; 24(1): 1082, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39223545

RESUMO

BACKGROUND: Colorectal cancer is the third most common cancer and the second leading cause of cancer death. There are limited therapeutic options for the treatment of locally advanced or metastatic colorectal cancers which fail first-line chemotherapy. Phase I/II studies showed that the combined application of the raltitrexed and irinotecan has significant synergistic effect and acceptable toxicity. However, most of these previous studies have relatively small sample size. METHODS: This is a prospective open-label, single-arm, multi-center, Phase II trial. Brief inclusion criteria: patients were aged 18 to 75 years with locally advanced or metastatic colorectal cancer after failure of 5-FU and oxaliplatin therapy. Enrolled patients received raltitrexed (3 mg/m2, d1) and irinotecan (180 mg/m2, d1) each 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, and the secondary endpoints were disease control rate, objective response rate, overall survival and safety. RESULTS: A total of 108 patients were enrolled between September 2016 and May 2020. The median age was 61 years, ECOG 1 score accounts for 67.6%, the rest were ECOG 0. A total of 502 cycles were completed, with an average of 4.6 cycles and a median of 4 cycles. 108 patients were evaluated, with an objective response rate of 17.6%, and disease control rate of 76.9%. The median follow-up time was 27 months (range:3.1-61.0 m) at data cut-off on March 2023. Median progression-free survival was 4.9 months (95% CI 4.1-5.7) and median overall survival was 13.1 months (95% CI 12.2-15.5). The most common adverse events that were elevated are alanine aminotransferase increased, aspartate aminotransferase increased, fatigue, diarrhoea, neutrocytopenia, thrombocytopenia, hypohemoglobin, and leukocytopenia. Most of the adverse events were Grade I/II, which were relieved after symptomatic treatment, and there were no treatment-related cardiotoxicities and deaths. CONCLUSIONS: The combination of raltitrexed and irinotecan as second-line treatment for mCRC could be a reliable option after failure of standard 5-Fu-first-line chemotherapy in locally advanced or metastatic colorectal cancers, especially for patients with 5-FU intolerance (cardiac events or DPD deficiency patients). TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03053167, registration date was 14/2/2017.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorretais , Irinotecano , Quinazolinas , Tiofenos , Humanos , Pessoa de Meia-Idade , Quinazolinas/uso terapêutico , Quinazolinas/efeitos adversos , Masculino , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/mortalidade , Irinotecano/uso terapêutico , Irinotecano/administração & dosagem , Idoso , Feminino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Tiofenos/uso terapêutico , Tiofenos/administração & dosagem , Tiofenos/efeitos adversos , Estudos Prospectivos , Adulto , Intervalo Livre de Progressão , Adulto Jovem
15.
BMC Cardiovasc Disord ; 24(1): 319, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38914951

RESUMO

BACKGROUND: Percutaneous coronary intervention (PCI) with primary stenting, which stands for stent implantation regardless of obtaining satisfactory results with balloon angioplasty, has superseded conventional plain old balloon angioplasty with provisional stenting. With drug-coated balloon (DCB), primary DCB angioplasty with provisional stenting has shown non-inferiority to primary stenting for de novo coronary small vessel disease. However, the long-term efficacy and safety of such a strategy to the primary stenting on clinical endpoints in de novo lesions without vessel diameter restrictions remain uncertain. STUDY DESIGN: The REC-CAGEFREE I is an investigator-initiated, multicenter, randomized, open-label trial aimed to enroll 2270 patients with acute or chronic coronary syndrome from 43 interventional cardiology centers in China to evaluate the non-inferiority of primary paclitaxel-coated balloons angioplasty to primary stenting for the treatment of de novo, non-complex lesions without vessel diameter restrictions. Patients who fulfill all the inclusion and exclusion criteria and have achieved a successful lesion pre-dilatation will be randomly assigned to the two arms in a 1:1 ratio. Protocol-guided DCB angioplasty and bailout stenting after unsatisfactory angioplasty are mandatory in the primary DCB angioplasty group. The second-generation sirolimus-eluting stent will be used as a bailout stent in the primary DCB angioplasty group and the treatment device in the primary stenting group. The primary endpoint is the incidence of Device-oriented Composite Endpoint (DoCE) within 24 months after randomization, including cardiac death, target vessel myocardial infarction, and clinically and physiologically indicated target lesion revascularization. DISCUSSION: The ongoing REC-CAGEFREE I trial is the first randomized trial with a clinical endpoint to assess the efficacy and safety of primary DCB angioplasty for the treatment of de novo, non-complex lesions without vessel diameter restrictions. If non-inferiority is shown, PCI with primary DCB angioplasty could be an alternative treatment option to primary stenting. TRIAL REGISTRATION: Registered on clinicaltrial.gov (NCT04561739).


Assuntos
Angioplastia Coronária com Balão , Cateteres Cardíacos , Fármacos Cardiovasculares , Materiais Revestidos Biocompatíveis , Doença da Artéria Coronariana , Paclitaxel , Humanos , Angioplastia Coronária com Balão/instrumentação , Angioplastia Coronária com Balão/efeitos adversos , Angioplastia Coronária com Balão/mortalidade , Resultado do Tratamento , Fármacos Cardiovasculares/administração & dosagem , Fármacos Cardiovasculares/efeitos adversos , China , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Doença da Artéria Coronariana/terapia , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Fatores de Tempo , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Stents , Idoso , Stents Farmacológicos , Estudos de Equivalência como Asunto , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
Addict Biol ; 29(2): e13367, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38380757

RESUMO

Alcohol use disorder (AUD) has been associated with attentional deficits and impairments of working memory. Meanwhile, attention and working memory are critical for time perception. However, it remains unclear how time perception alters in AUD patients and how attention and working memory affect their time perception. The current study aims to clarify the time perception characteristics of AUD patients and the cognitive mechanisms underlying their time perception dysfunction. Thirty-one patients (three of them were excluded) with AUD and thirty-one matched controls completed the Time Bisection Task, Attention Network Test and Digital Span Backward Test to assess their abilities in time perception, attention network and working memory, respectively. The results showed that, after controlling for anxiety, depression, and impulsivity, AUD patients had a lower proportion of 'long' responses at intervals of 600, 750, 900, 1050 and 1200 ms. Furthermore, they displayed higher subjective equivalence points and higher Weber ratios compared to controls. Moreover, AUD patients showed impaired alerting and executive control networks as well as reduced working memory resources. Only working memory resources mediated the impact of AUD on time perception. In conclusion, our findings suggested that the duration underestimation in AUD patients is predominantly caused by working memory deficits.


Assuntos
Alcoolismo , Percepção do Tempo , Humanos , Memória de Curto Prazo/fisiologia , Função Executiva/fisiologia , Consumo de Bebidas Alcoólicas
17.
BMC Med Imaging ; 24(1): 62, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38486185

RESUMO

OBJECTIVE: Early diagnosis of osteoporosis is crucial to prevent osteoporotic vertebral fracture and complications of spine surgery. We aimed to conduct a hybrid transformer convolutional neural network (HTCNN)-based radiomics model for osteoporosis screening in routine CT. METHODS: To investigate the HTCNN algorithm for vertebrae and trabecular segmentation, 92 training subjects and 45 test subjects were employed. Furthermore, we included 283 vertebral bodies and randomly divided them into the training cohort (n = 204) and test cohort (n = 79) for radiomics analysis. Area receiver operating characteristic curves (AUCs) and decision curve analysis (DCA) were applied to compare the performance and clinical value between radiomics models and Hounsfield Unit (HU) values to detect dual-energy X-ray absorptiometry (DXA) based osteoporosis. RESULTS: HTCNN algorithm revealed high precision for the segmentation of the vertebral body and trabecular compartment. In test sets, the mean dice scores reach 0.968 and 0.961. 12 features from the trabecular compartment and 15 features from the entire vertebral body were used to calculate the radiomics score (rad score). Compared with HU values and trabecular rad-score, the vertebrae rad-score suggested the best efficacy for osteoporosis and non-osteoporosis discrimination (training group: AUC = 0.95, 95%CI 0.91-0.99; test group: AUC = 0.97, 95%CI 0.93-1.00) and the differences were significant in test group according to the DeLong test (p < 0.05). CONCLUSIONS: This retrospective study demonstrated the superiority of the HTCNN-based vertebrae radiomics model for osteoporosis discrimination in routine CT.


Assuntos
Osteoporose , Fraturas por Osteoporose , Humanos , Absorciometria de Fóton , Densidade Óssea , Vértebras Lombares/diagnóstico por imagem , Redes Neurais de Computação , Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/diagnóstico por imagem , Radiômica , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Distribuição Aleatória
18.
Sensors (Basel) ; 24(8)2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38676083

RESUMO

The rapid development of deep neural networks has attracted significant attention in the infrared and visible image fusion field. However, most existing fusion models have many parameters and consume high computational and spatial resources. This paper proposes a fast and efficient recursive fusion neural network model to solve this complex problem that few people have touched. Specifically, we designed an attention module combining a traditional fusion knowledge prior with channel attention to extract modal-specific features efficiently. We used a shared attention layer to perform the early fusion of modal-shared features. Adopting parallel dilated convolution layers further reduces the network's parameter count. Our network is trained recursively, featuring minimal model parameters, and requires only a few training batches to achieve excellent fusion results. This significantly reduces the consumption of time, space, and computational resources during model training. We compared our method with nine SOTA methods on three public datasets, demonstrating our method's efficient training feature and good fusion results.

19.
Sensors (Basel) ; 24(14)2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39065953

RESUMO

Pavement condition monitoring is an important task in road asset management and efficient abnormal pavement condition detection is critical for timely conservation management decisions. The present work introduces a mobile pavement condition monitoring approach utilizing low-cost sensor technology and machine-learning-based methodologies. Specifically, an on-board unit (OBU) embedded with an inertial measurement unit (IMU) and global positioning system (GPS) is applied to collect vehicle posture data in real time. Through a comprehensive analysis of both time domain and frequency domain data features for both normal and abnormal pavement conditions, feature engineering is conducted to identify how the most important features affect abnormal pavement condition recognition. Six machine learning models are then developed to identify different types of pavement conditions. The performance of different algorithms and the significance of different features are then analyzed. Moreover, the influence of vehicle speed on pavement condition assessment is further examined and classification models for different speed intervals are developed. The results indicate that the random forest (RF) model that considers vehicle speed achieves the best performance in pavement condition monitoring. The outcomes of the present work would contribute to cost-effective pavement condition monitoring and provide an important reference for pavement maintenance sectors.

20.
JAMA ; 331(3): 201-211, 2024 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-38227033

RESUMO

Importance: Adjuvant and neoadjuvant immunotherapy have improved clinical outcomes for patients with early-stage non-small cell lung cancer (NSCLC). However, the optimal combination of checkpoint inhibition with chemotherapy remains unknown. Objective: To determine whether toripalimab in combination with platinum-based chemotherapy will improve event-free survival and major pathological response in patients with stage II or III resectable NSCLC compared with chemotherapy alone. Design, Setting, and Participants: This randomized clinical trial enrolled patients with stage II or III resectable NSCLC (without EGFR or ALK alterations for nonsquamous NSCLC) from March 12, 2020, to June 19, 2023, at 50 participating hospitals in China. The data cutoff date for this interim analysis was November 30, 2022. Interventions: Patients were randomized in a 1:1 ratio to receive 240 mg of toripalimab or placebo once every 3 weeks combined with platinum-based chemotherapy for 3 cycles before surgery and 1 cycle after surgery, followed by toripalimab only (240 mg) or placebo once every 3 weeks for up to 13 cycles. Main Outcomes and Measures: The primary outcomes were event-free survival (assessed by the investigators) and the major pathological response rate (assessed by blinded, independent pathological review). The secondary outcomes included the pathological complete response rate (assessed by blinded, independent pathological review) and adverse events. Results: Of the 501 patients randomized, 404 had stage III NSCLC (202 in the toripalimab + chemotherapy group and 202 in the placebo + chemotherapy group) and 97 had stage II NSCLC and were excluded from this interim analysis. The median age was 62 years (IQR, 56-65 years), 92% of patients were male, and the median follow-up was 18.3 months (IQR, 12.7-22.5 months). For the primary outcome of event-free survival, the median length was not estimable (95% CI, 24.4 months-not estimable) in the toripalimab group compared with 15.1 months (95% CI, 10.6-21.9 months) in the placebo group (hazard ratio, 0.40 [95% CI, 0.28-0.57], P < .001). The major pathological response rate (another primary outcome) was 48.5% (95% CI, 41.4%-55.6%) in the toripalimab group compared with 8.4% (95% CI, 5.0%-13.1%) in the placebo group (between-group difference, 40.2% [95% CI, 32.2%-48.1%], P < .001). The pathological complete response rate (secondary outcome) was 24.8% (95% CI, 19.0%-31.3%) in the toripalimab group compared with 1.0% (95% CI, 0.1%-3.5%) in the placebo group (between-group difference, 23.7% [95% CI, 17.6%-29.8%]). The incidence of immune-related adverse events occurred more frequently in the toripalimab group. No unexpected treatment-related toxic effects were identified. The incidence of grade 3 or higher adverse events, fatal adverse events, and adverse events leading to discontinuation of treatment were comparable between the groups. Conclusions and Relevance: The addition of toripalimab to perioperative chemotherapy led to a significant improvement in event-free survival for patients with resectable stage III NSCLC and this treatment strategy had a manageable safety profile. Trial Registration: ClinicalTrials.gov Identifier: NCT04158440.


Assuntos
Anticorpos Monoclonais Humanizados , Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Compostos de Platina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Resposta Patológica Completa , Antineoplásicos/uso terapêutico , Terapia Combinada , Compostos de Platina/administração & dosagem , Compostos de Platina/uso terapêutico , Idoso
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