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1.
Iran J Public Health ; 53(3): 634-643, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38919311

RESUMO

Background: We aimed to explore the epidemiological trends and characteristics of undernutrition among children and adolescents aged 7~18 years in Macao from 2005 to 2020 to provide insights into the improvement of nutritional status among the youth in Macao, China. Methods: Based on the data collected from the Citizen Physical Fitness surveillance sessions in Macao in 2005, 2010, 2015, and 2020, the prevalence of undernutrition among children and adolescents aged 7~18 years in Macao was calculated. Result: In 2020, the prevalence of undernutrition among children and adolescents aged 7~18 years in Macao was 12.11%. Among them, the rates of stunting, moderate or severe wasting, and mild wasting were 0.63%, 5.25%, and 6.23%, respectively. The prevalence of undernutrition among boys (13.81%) was higher than that among girls (10.06%). Mild wasting was the main form of undernutrition among students. From 2005 to 2020, the prevalence of malnutrition showed a decreasing trend (P<0.05), but there was a rebound in 2020 from 2015, mainly because it may be caused by the COVID-19 pandemic in 2020. The prevalence of undernutrition among children and adolescents in Macao was lower than that in Mainland China (P<0.01). Conclusion: The detection rates of undernutrition showed a decreasing trend from 2005 to 2020. In the post-pandemic era, Macao should undertake more effective measures in areas such as promoting balanced nutritional intake, increasing physical activity levels, enhancing school physical education, and incorporating mental health education. These efforts are essential for further reducing the prevalence of undernutrition among children and adolescents.

2.
J Med Chem ; 67(12): 10336-10349, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38836467

RESUMO

While large-scale artificial intelligence (AI) models for protein structure prediction and design are advancing rapidly, the translation of deep learning models for practical macromolecular drug development remains limited. This investigation aims to bridge this gap by combining cutting-edge methodologies to create a novel peptide-based PROTAC drug development paradigm. Using ProteinMPNN and RFdiffusion, we identified binding peptides for androgen receptor (AR) and Von Hippel-Lindau (VHL), followed by computational modeling with Alphafold2-multimer and ZDOCK to predict spatial interrelationships. Experimental validation confirmed the designed peptide's binding ability to AR and VHL. Transdermal microneedle patching technology was seamlessly integrated for the peptide PROTAC drug delivery in androgenic alopecia treatment. In summary, our approach provides a generic method for generating peptide PROTACs and offers a practical application for designing potential therapeutic drugs for androgenetic alopecia. This showcases the potential of interdisciplinary approaches in advancing drug development and personalized medicine.


Assuntos
Alopecia , Desenho de Fármacos , Peptídeos , Receptores Androgênicos , Alopecia/tratamento farmacológico , Receptores Androgênicos/metabolismo , Receptores Androgênicos/química , Humanos , Peptídeos/química , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Animais , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo , Proteína Supressora de Tumor Von Hippel-Lindau/química , Masculino
3.
Adv Mater ; : e2310659, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38871360

RESUMO

Layered iron/manganese-based oxides are a class of promising cathode materials for sustainable batteries due to their high energy densities and earth abundance. However, the stabilization of cationic and anionic redox reactions in these cathodes during cycling at high voltage remain elusive. Here, an electrochemically/thermally stable P2-Na0.67Fe0.3Mn0.5Mg0.1Ti0.1O2 cathode material with zero critical elements is designed for sodium-ion batteries (NIBs) to realize a highly reversible capacity of ≈210 mAh g-1 at 20 mA g-1 and good cycling stability with a capacity retention of 74% after 300 cycles at 200 mA g-1, even when operated with a high charge cut-off voltage of 4.5 V versus sodium metal. Combining a suite of cutting-edge characterizations and computational modeling, it is shown that Mg/Ti co-doping leads to stabilized surface/bulk structure at high voltage and high temperature, and more importantly, enhances cationic/anionic redox reaction reversibility over extended cycles with the suppression of other undesired oxygen activities. This work fundamentally deepens the failure mechanism of Fe/Mn-based layered cathodes and highlights the importance of dopant engineering to achieve high-energy and earth-abundant cathode material for sustainable and long-lasting NIBs.

4.
JTO Clin Res Rep ; 5(6): 100678, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38846810

RESUMO

Introduction: The available approved anticancer drugs for Chinese patients are relatively limited because of China's low participation rate in international clinical trials. Therefore, a focus on approved anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) drugs in China is needed. This study aims to assess the heterogeneity of anti-PD-1/PD-L1 antibodies manufactured in China (domestic PD-1/PD-L1) and overseas (imported PD-1/PD-L1) when combined with chemotherapy as the first-line treatment of NSCLC. Methods: A systematic search was performed using PubMed, EMBASE, and Cochrane Library of publications up to July 13, 2023. Meta-analysis was applied to compare the efficacy and safety profile between anti-PD-1/PD-L1 antibodies plus chemotherapy (PD-1/PD-L1+Chemo) and chemotherapy alone using STATA software. Pooled hazard ratios for progression-free survival and overall survival, odds ratios for objective response rate, and incidence rate of grade greater than or equal to three treatment-related adverse events with 95% confidence intervals were calculated in the domestic group and imported group by a random-effects model, and the heterogeneity between the two estimates was assessed. Results: There were 14 eligible clinical studies with a total of 3951 patients involved in this analysis, including eight studies of domestic PD-1/PD-L1+Chemo and six studies of imported PD-1/PD-L1+Chemo. The study revealed that there was no significant difference between domestic and imported PD-1/PD-L1+Chemo in overall survival (p = 0.80), progression-free survival (p = 0.53), and incidence rate of grade greater than or equal to three treatment-related adverse events (p = 0.10). Nevertheless, the objective response rate of imported PD-1/PD-L1+Chemo was significantly higher than that of domestic PD-1/PD-L1+Chemo (p = 0.03). Conclusions: Domestic anti-PD-1/PD-L1 antibodies plus chemotherapy were found to have comparable efficacy and safety to those combined with imported anti-PD-1/PD-L1 antibodies based on current evidence.

5.
Drug Resist Updat ; 76: 101096, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38924996

RESUMO

Krüppel-like factor 12 (KLF12) has been characterized as a transcriptional repressor, and previous studies have unveiled its roles in angiogenesis, neural tube defect, and natural killer (NK) cell proliferation. However, the contribution of KLF12 to cancer treatment remains undefined. Here, we show that KLF12 is downregulated in various cancer types, and KLF12 downregulation promotes cisplatin resistance and cancer metastasis in esophageal squamous cell carcinoma (ESCC). Mechanistically, KLF12 binds to the promoters of L1 Cell Adhesion Molecule (L1CAM) and represses its expression. Depletion of L1CAM abrogates cisplatin resistance and cancer metastasis caused by KLF12 loss. Moreover, the E3 ubiquitin ligase tripartite motif-containing 27 (TRIM27) binds to the N-terminal region of KLF12 and ubiquitinates KLF12 at K326 via K33-linked polyubiquitination. Notably, TRIM27 depletion enhances the transcriptional activity of KLF12 and consequently inhibits L1CAM expression. Overall, our study elucidated a novel regulatory mechanism involving TRIM27, KLF12 and L1CAM, which plays a substantial role in cisplatin resistance and cancer metastasis in ESCC. Targeting these genes could be a promising approach for ESCC treatment.

7.
Transl Lung Cancer Res ; 13(4): 821-838, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38736484

RESUMO

Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide, and lymph node dissection (LND) is a significant surgical procedure employed in its management. Although some studies suggest benefits of LND, the extent of its impact on survival, the optimal range of lymph nodes to be examined, and the specific patient groups that benefit most remain areas of active debate and investigation. Methods: A population-based analysis was conducted using the Surveillance, Epidemiology, and End Results (SEER) database. Patients diagnosed with NSCLC between 2004 and 2017, undergoing primary tumor resection, were included. Descriptive, univariate, and multivariate analyses assessed the effect of LND on survival, and a restricted cubic spline method determined the optimal range for lymph node examination. Results: This study of 37,323 NSCLC patients delved into the impact of LND on lung cancer-specific survival. Key findings revealed a median survival of 19.58 months, with 85% mortality. Baseline characteristics included a majority of White patients (81%), distant stage diagnoses (63%), and 64% with Grade IV tumors. LND emerged as a crucial predictor, influencing survival across age, gender, race, and tumor characteristics. Univariate analysis highlighted its significance, with higher T, N, and M categories, advanced stage, and poorer grade associating with elevated hazard ratios. Multivariate Cox proportional hazards (PH) analysis reinforced LND's impact, showcasing lower hazard ratios post-removal. Hazard ratios for biopsy/aspiration and removal of regional lymph nodes were 0.85 [95% confidence interval (CI): 0.81-0.89; P<0.001] and 0.43 (95% CI: 0.39-0.46; P<0.001), underscoring the protective effect. Visualizations and a U-shaped curve analysis identified an optimal range (24-32 nodes) for examination, emphasizing the nuanced benefits across NSCLC stages. Conclusions: The study findings suggest that LND plays a critical role in improving cancer-specific survival in NSCLC patients, particularly when tailored to the early stages of the disease. The optimal range of lymph nodes examined, between 24 and 32, offers crucial insights for personalized NSCLC treatment strategies and may enhance overall survival. These results underscore the need for refined surgical guidelines that incorporate the extent of LND, supporting the utility of a more personalized approach in NSCLC management.

8.
Oncogene ; 43(26): 2025-2037, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38744954

RESUMO

Lung adenocarcinoma (LUAD) is one of the most prevalent types of cancer. Ubiquitination is crucial in modulating cell proliferation and aerobic glycolysis in cancer. The frequency of TP53 mutations in LUAD is approximately 50%. Currently, therapeutic targets for wild-type (WT) p53-expressing LUAD are limited. In the present study, we systemically explored the expression of ubiquitin-specific protease genes using public datasets. Then, we focused on ubiquitin-specific protease 54 (USP54), and explored its prognostic significance in LUAD patients using public datasets, analyses, and an independent cohort from our center. We found that the expression of USP54 was lower in LUAD tissues compared with that in the paracancerous tissues. Low USP54 expression levels were linked to a malignant phenotype and worse survival in patients with LUAD. The results of functional experiments revealed that up-regulation of USP54 suppressed LUAD cell proliferation in vivo and in vitro. USP54 directly interacted with p53 protein and the levels of ubiquitinated p53 were inversely related to USP54 levels, consistent with a role of USP54 in deubiquitinating p53 in p53-WT LUAD cells. Moreover, up-regulation of the USP54 expression inhibited aerobic glycolysis in LUAD cells. Importantly, we confirmed that USP54 inhibited aerobic glycolysis and the growth of tumor cells by a p53-mediated decrease in glucose transporter 1 (GLUT1) expression in p53-WT LUAD cells. Altogether, we determined a novel mechanism of survival in the p53-WT LUAD cells to endure the malnourished tumor microenvironment and provided insights into the role of USP54 in the adaptation of p53-WT LUAD cells to metabolic stress.


Assuntos
Adenocarcinoma de Pulmão , Transportador de Glucose Tipo 1 , Glicólise , Neoplasias Pulmonares , Proteína Supressora de Tumor p53 , Humanos , Transportador de Glucose Tipo 1/metabolismo , Transportador de Glucose Tipo 1/genética , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Glicólise/genética , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Animais , Camundongos , Proliferação de Células/genética , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Masculino , Proteases Específicas de Ubiquitina/metabolismo , Proteases Específicas de Ubiquitina/genética , Prognóstico , Ubiquitinação , Regulação Neoplásica da Expressão Gênica , Proteólise , Camundongos Nus
9.
Cancer Rep (Hoboken) ; 7(5): e2003, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38703000

RESUMO

BACKGROUND: Mid-rectal cancer treatment traditionally involves conventional laparoscopic-assisted resection (CLAR). This study aimed to assess the clinical and therapeutic advantages of Natural Orifice Specimen Extraction Surgery (NOSES) over CLAR. AIMS: To compare the clinical outcomes, intraoperative metrics, postoperative recovery, complications, and long-term prognosis between NOSES and CLAR groups. MATERIALS & METHODS: A total of 136 patients were analyzed, with 92 undergoing CLAR and 44 undergoing NOSES. Clinical outcomes were evaluated, and propensity score matching (PSM) was employed to control potential biases. RESULTS: The NOSES group exhibited significant improvements in postoperative recovery, including lower pain scores on days 1, 3, and 5 (p < .001), reduced need for additional analgesics (p = .02), shorter hospital stays (10.8 ± 2.3 vs. 14.2 ± 5.3 days; p < .001), and decreased intraoperative blood loss (48.1 ± 52.7 mL vs. 71.0 ± 55.0 mL; p = .03). Patients undergoing NOSES also reported enhanced satisfaction with postoperative abdominal appearance and better quality of life. Additionally, the NOSES approach resulted in fewer postoperative complications. CONCLUSION: While long-term outcomes (overall survival, disease-free survival, and local recurrence rates) were comparable between the two methods, NOSES demonstrated superior postoperative outcomes compared to CLAR in mid-rectal cancer treatment, while maintaining similar long-term oncological safety. These findings suggest that NOSES could serve as an effective alternative to CLAR without compromising long-term results.


Assuntos
Laparoscopia , Cirurgia Endoscópica por Orifício Natural , Neoplasias Retais , Humanos , Feminino , Laparoscopia/métodos , Laparoscopia/efeitos adversos , Masculino , Neoplasias Retais/cirurgia , Neoplasias Retais/patologia , Neoplasias Retais/mortalidade , Pessoa de Meia-Idade , Idoso , Cirurgia Endoscópica por Orifício Natural/métodos , Cirurgia Endoscópica por Orifício Natural/efeitos adversos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Tempo de Internação/estatística & dados numéricos , Resultado do Tratamento , Qualidade de Vida , Pontuação de Propensão
11.
Int J Mol Sci ; 25(7)2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38612682

RESUMO

Squalene epoxidase (SQLE) is a key enzyme in the mevalonate-cholesterol pathway that plays a critical role in cellular physiological processes. It converts squalene to 2,3-epoxysqualene and catalyzes the first oxygenation step in the pathway. Recently, intensive efforts have been made to extend the current knowledge of SQLE in cancers through functional and mechanistic studies. However, the underlying mechanisms and the role of SQLE in cancers have not been fully elucidated yet. In this review, we retrospected current knowledge of SQLE as a rate-limiting enzyme in the mevalonate-cholesterol pathway, while shedding light on its potential as a diagnostic and prognostic marker, and revealed its therapeutic values in cancers. We showed that SQLE is regulated at different levels and is involved in the crosstalk with iron-dependent cell death. Particularly, we systemically reviewed the research findings on the role of SQLE in different cancers. Finally, we discussed the therapeutic implications of SQLE inhibitors and summarized their potential clinical values. Overall, this review discussed the multifaceted mechanisms that involve SQLE to present a vivid panorama of SQLE in cancers.


Assuntos
Neoplasias , Esqualeno Mono-Oxigenase , Humanos , Morte Celular , Colesterol , Ácido Mevalônico , Neoplasias/genética , Esqualeno Mono-Oxigenase/genética
12.
Small ; : e2312288, 2024 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-38431966

RESUMO

The development of capable of simultaneously modulating the sluggish electrochemical kinetics, shuttle effect, and lithium dendrite growth is a promising strategy for the commercialization of lithium-sulfur batteries. Consequently, an elaborate preparation method is employed to create a host material consisting of multi-channel carbon microspheres (MCM) containing highly dispersed heterostructure Fe3 O4 -FeTe nanoparticles. The Fe3 O4 -FeTe@MCM exhibits a spontaneous built-in electric field (BIEF) and possesses both lithophilic and sulfophilic sites, rendering it an appropriate host material for both positive and negative electrodes. Experimental and theoretical results reveal that the existence of spontaneous BIEF leads to interfacial charge redistribution, resulting in moderate polysulfide adsorption which facilitates the transfer of polysulfides and diffusion of electrons at heterogeneous interfaces. Furthermore, the reduced conversion energy barriers enhanced the catalytic activity of Fe3 O4 -FeTe@MCM for expediting the bidirectional sulfur conversion. Moreover, regulated Li deposition behavior is realized because of its high conductivity and remarkable lithiophilicity. Consequently, the battery exhibited long-term stability for 500 cycles with 0.06% capacity decay per cycle at 5 C, and a large areal capacity of 7.3 mAh cm-2 (sulfur loading: 9.73 mg cm-2 ) at 0.1 C. This study provides a novel strategy for the rational fabrication of heterostructure hosts for practical Li-S batteries.

13.
Int J Mol Sci ; 25(3)2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38338920

RESUMO

Sarcomas are heterogeneous connective tissue malignancies that have been historically categorized into soft tissue and bone cancers. Although multimodal therapies are implemented, many sarcoma subtypes are still difficult to treat. Lipids play vital roles in cellular activities; however, ectopic levels of lipid metabolites have an impact on tumor recurrence, metastasis, and drug resistance. Thus, precision therapies targeting lipid metabolism in sarcoma need to be explored. In this study, we performed a comprehensive analysis of molecular stratification based on lipid metabolism-associated genes (LMAGs) using both public datasets and the data of patients in our cohort and constructed a novel prognostic model consisting of squalene epoxidase (SQLE) and tumor necrosis factor (TNF). We first integrated information on gene expression profile and survival outcomes to divide TCGA sarcoma patients into high- and low-risk subgroups and further revealed the prognosis value of the metabolic signature and immune infiltration of patients in both groups, thus proposing various therapeutic recommendations for sarcoma. We observed that the low-risk sarcoma patients in the TCGA-SARC cohort were characterized by high proportions of immune cells and increased expression of immune checkpoint genes. Subsequently, this lipid metabolic signature was validated in four external independent sarcoma datasets including the CHCAMS cohort. Notably, SQLE, a rate-limiting enzyme in cholesterol biosynthesis, was identified as a potential therapeutic target for sarcoma. Knockdown of SQLE substantially inhibited cell proliferation and colony formation while promoting the apoptosis of sarcoma cells. Terbinafine, an inhibitor of SQLE, displayed similar tumor suppression capacity in vitro. The prognostic predictive model and the potential drug target SQLE might serve as valuable hints for further in-depth biological, diagnostic, and therapeutic exploration of sarcoma.


Assuntos
Sarcoma , Transcriptoma , Humanos , Metabolismo dos Lipídeos/genética , Recidiva Local de Neoplasia , Sarcoma/tratamento farmacológico , Sarcoma/genética , Lipídeos
14.
Adv Sci (Weinh) ; 11(13): e2302782, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38287891

RESUMO

The recent development of wearable devices is revolutionizing the way of human-machine interaction (HMI). Nowadays, an interactive interface that carries more embedded information is desired to fulfill the increasing demand in era of Internet of Things. However, present approach normally relies on sensor arrays for memory expansion, which inevitably brings the concern of wiring complexity, signal differentiation, power consumption, and miniaturization. Herein, a one-channel based self-powered HMI interface, which uses the eigenfrequency of magnetized micropillar (MMP) as identification mechanism, is reported. When manually vibrated, the inherent recovery of the MMP causes a damped oscillation that generates current signals because of Faraday's Law of induction. The time-to-frequency conversion explores the MMP-related eigenfrequency, which provides a specific solution to allocate diverse commands in an interference-free behavior even with one electric channel. A cylindrical cantilever model is built to regulate the MMP eigenfrequencies via precisely designing the dimensional parameters and material properties. It is shown that using one device and two electrodes, high-capacity HMI interface can be realized when the magnetic micropillars (MMPs) with different eigenfrequencies have been integrated. This study provides the reference value to design the future HMI system especially for situations that require a more intuitive and intelligent communication experience with high-memory demand.

15.
Pharmacol Res ; 200: 107060, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38185210

RESUMO

OBJECTIVE: To assess the efficacy and safety of FDA-approved KRASG12C inhibitors in patients with KRASG12C-mutated solid tumors. METHODS: We searched PubMed, EMBASE, Cochrane Library, and major international conferences for clinical trials published in English up to March 6, 2023. Clinical trials investigating sotorasib or adagrasib and reporting the clinical outcomes of the objective response rate (ORR), disease control rate (DCR), or incidence rate of grade ≥ 3 adverse events (AEs) were eligible. The primary endpoint was the ORR. Secondary endpoints included the DCR, incidence rate of grade ≥ 3 AEs, and odds ratio (OR) of the ORR between patients with or without co-mutation. The Random-effects model was applied for the outcomes of interest. RESULTS: 18 studies with 1224 patients were included in this meta-analysis. The pooled ORR, DCR, and incidence rate of grade ≥ 3 AEs were 31 % (95 % CI, 25-37 %), 86 % (95 % CI, 82-89 %), and 29 % (95 % CI, 23-36 %), respectively. KRASG12C-mutated NSCLC patients with a co-mutation of KEAP1 exhibited a worse ORR than those with wild-type KEAP1 (OR: 0.35, 95 % CI: 0.16-0.77). CONCLUSIONS: This study provided a comprehensive understanding of the efficacy and safety of KRASG12C inhibitors in treating solid tumors and identified KEAP1 mutation as a potential predictive biomarker of inferior response in patients treated with KRASG12C inhibitors. These findings may assist in the design of future clinical trials for identifying populations that may benefit from KRASG12C inhibitor treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch , Proteínas Proto-Oncogênicas p21(ras) , Fator 2 Relacionado a NF-E2 , Mutação
16.
Plant Cell Rep ; 43(1): 4, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38117314

RESUMO

KEY MESSAGE: The leaf hyponasty response depends on tip-to-petiole auxin transport. This transport can happen through two parallel pathways: active trans-membrane transport mediated by PIN proteins and passive diffusion through plasmodesmata. A plant's ability to counteract potential shading by neighboring plants depends on transport of the hormone auxin. Neighbor sensing at the leaf tip triggers auxin production. Once this auxin reaches the abaxial petiole epidermis, it causes cell elongation, which leads to leaf hyponasty. Two pathways are known to contribute to this intercellular tip-to-petiole auxin movement: (i) transport facilitated by plasma membrane-localized PIN auxin transporters and (ii) diffusion enabled by plasmodesmata. We tested if these two modes of transport are arranged sequentially or in parallel. Moreover, we investigated if they are functionally linked. Mutants in which one of the two pathways is disrupted indicated that both pathways are necessary for a full hyponasty response. Visualization of PIN3-GFP and PIN7-GFP localization indicated PIN-mediated transport in parallel to plasmodesmata-mediated transport along abaxial midrib epidermis cells. We found plasmodesmata-mediated cell coupling in the pin3pin4pin7 mutant to match wild-type levels, indicating no redundancy between pathways. Similarly, PIN3, PIN4 and PIN7 mRNA levels were unaffected in a mutant with disrupted plasmodesmata pathway. Our results provide mechanistic insight on leaf hyponasty, which might facilitate the manipulation of the shade avoidance response in crops.


Assuntos
Arabidopsis , Arabidopsis/genética , Plasmodesmos , Transporte Biológico , Proteínas de Membrana Transportadoras/genética , Ácidos Indolacéticos
17.
Mol Cancer ; 22(1): 157, 2023 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-37770864

RESUMO

BACKGROUND: Although colonoscopy is the standard screening test for colorectal cancer (CRC), its use is limited by a poor compliance rate, the need for extensive bowel preparation, and the risk of complications. As an alternative, an FDA-approved stool-based DNA test, Cologuard, has demonstrated satisfactory detection performance for CRC, but its compliance rate remains suboptimal, primarily attributable to individuals' reluctance to provide stool samples. METHODS: We developed a noninvasive blood-based CRC test, ColonSecure, based on cell-free DNA containing cancer-specific CpG island methylation patterns. We initially screened publicly available datasets for differentially methylated CpG sites in CRC with prediction potential. Subsequently, we performed two sequential bisulfite-free methylation sequencing on blood samples obtained from CRC patients and non-cancer controls. Through rigorous evaluation of each marker and machine learning-assisted feature selection, we identified 149 hypermethylated markers from over 193,000 CpG sites. These markers were then utilized to construct the ColonSecure model, enabling accurate CRC detection. RESULTS: We validated the efficacy of our cell-free DNA methylation-based blood test for CRC screening with 3493 high-risk individuals identified from 114,136 urban residents. The ColonSecure test identified 89 out of 103 CRC patients diagnosed by the follow-up colonoscopy, outperforming CEA, CRP, and CA19-9 (with a sensitivity of 86.4% compared to 45.6%, 39.8%, and 25.2% for CEA, CRP, and CA19-9 respectively; an AUROC of 0.956 compared to an AUROC of < 0.77 for other methods). CONCLUSION: Our observations emphasize the potential of our multiple cfDNA methylation marker-based test for CRC screening in high-risk populations.


Assuntos
Ácidos Nucleicos Livres , Neoplasias Colorretais , Humanos , Metilação de DNA , Ácidos Nucleicos Livres/genética , Estudos Prospectivos , Antígeno CA-19-9 , Detecção Precoce de Câncer , Ilhas de CpG , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Biomarcadores Tumorais/genética
18.
Nano Lett ; 23(17): 7805-7814, 2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37651260

RESUMO

Lithium (Li) metal is regarded as the "Holy Grail" of anodes for high-energy rechargeable lithium batteries by virtue of its ultrahigh theoretical specific capacity and the lowest redox potential. However, the Li dendrite impedes the practical application of Li metal anodes. Herein, lithiophilic three-dimensional Cu-CuSn porous framework (3D Cu-CuSn) was fabricated by a vapor phase dealloying strategy via the difference in saturated vapor pressure between different metals and the Kirkendall effect. CuSn alloy sites were converted into LiSn alloy sites through the molten Li infusion method, and composite Li metal anodes (3D Cu-LiSn-Li) are achieved. Alloyed tin, as the bridge between the porous copper substrate and metallic Li, plays a critical role in optimizing Li nucleation and enhancing the fast lithium migration kinetics. This work demonstrates that lithiophilic binary copper alloys are an effective way to achieve room-temperature high rate performance and satisfied low-temperature cycling stability for Li metal batteries.

19.
ACS Appl Mater Interfaces ; 15(33): 39989-40000, 2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37613999

RESUMO

Superhydrophobic fabrics have recently attracted extensive interest not only in the fields of water-repellent clothing but also for the emerging functional fabrics due to their intrinsic flexibility and excellent stability. In this work, we proposed a simple, cost-effective, and environmentally friendly method to fabricate superhydrophobic fabrics with a broad application scope for textiles of different apertures. The flexible, breathable, and superhydrophobic fabric was realized via a three-step process, including polydimethylsiloxane (PDMS) encapsulation, in situ microcilia array formation, and silica nanoparticle decoration. With an adhesive PDMS layer and additive NdFeB particles, the hierarchical structures can tightly attach to the fabric substrate to provide robustness and durability. Specifically, the optimization of microcilia architecture was achieved via tuning the composite mass ratios so that suitable morphologies can be produced for robust nonwetting behavior. The superhydrophobic fabrics possess a contact angle and sliding angle of ∼155 and ∼3°, respectively, with excellent durability against 650 cycles' periodic mechanical abrasion, 130 cycles' tape-peeling test, washing evaluation, and chemical corrosions. Furthermore, the superhydrophobic fabric shows outstanding breathability and flexibility to be adaptive to surfaces with curvature or irregular shapes. The presented superhydrophobic strategy was considered to be feasible for multiple fabric substrates, revealing the broad application potential for fields of healthcare production, outdoor goods, catering industry, etc.

20.
Transl Lung Cancer Res ; 12(6): 1264-1275, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37425420

RESUMO

Background: Lung microbiome dysbiosis has been associated with lung carcinogenesis. However, the differences in the microbiome composition at different lung sites of lung cancer patients remain little understood. Studying the whole lung microbiome in cancer patients could provide new insights for interpreting the complex interplay between the microbiome and lung cancer and finding new targets for more effective therapies and preventive measures. Methods: A total of 16 patients with non-small cell lung cancer (NSCLC) were recruited for this study. Samples were obtained from four sites, including lung tumor tissues (TT), para-tumor tissues (PT), distal normal lung tissues (DN), and bronchial tissues (BT). The DNA was isolated from the tissues, and the V3-V4 regions were amplified. Sequencing libraries were generated and sequenced on an Illumina NovaSeq6000 platform. Results: The richness and evenness of the microbiome were generally consistent among the TT, PT, DN, and BT groups in lung cancer patients. Principal coordinate analysis (PCoA) and nonmetric multidimensional scaling (NMDS) based on Bray-Curtis, weighted and unweighted UniFrac distance showed no distinct separation trend among the four groups. Proteobacteria, Firmicutes, Bacteroidota, and Desulfobacterota were the most common phyla in all four groups, while TT showed the highest abundance of Proteobacteria and the lowest abundance of Firmicutes. At the genus level, Rubellimicrobium and Fictibacillus were higher in the TT group. In the predicted functional analysis by PICRUSt, there were no specifically discrepant pathways among the four groups. In addition, an inverse relationship between body mass index (BMI) and alpha diversity was observed in this study. Conclusions: A non-significant result was obtained from the microbiome diversity comparison between different tissues. However, we demonstrated that lung tumors were enriched with specific bacterial species, which might contribute to tumorigenesis. Moreover, we found an inverse relationship between BMI and alpha diversity in these tissues, providing a new clue for deciphering the mechanisms of lung carcinogenesis.

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