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1.
Nature ; 609(7927): 616-621, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35917926

RESUMO

The PIN-FORMED (PIN) protein family of auxin transporters mediates polar auxin transport and has crucial roles in plant growth and development1,2. Here we present cryo-electron microscopy structures of PIN3 from Arabidopsis thaliana in the apo state and in complex with its substrate indole-3-acetic acid and the inhibitor N-1-naphthylphthalamic acid (NPA). A. thaliana PIN3 exists as a homodimer, and its transmembrane helices 1, 2 and 7 in the scaffold domain are involved in dimerization. The dimeric PIN3 forms a large, joint extracellular-facing cavity at the dimer interface while each subunit adopts an inward-facing conformation. The structural and functional analyses, along with computational studies, reveal the structural basis for the recognition of indole-3-acetic acid and NPA and elucidate the molecular mechanism of NPA inhibition on PIN-mediated auxin transport. The PIN3 structures support an elevator-like model for the transport of auxin, whereby the transport domains undergo up-down rigid-body motions and the dimerized scaffold domains remain static.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Ácidos Indolacéticos , Apoproteínas/química , Apoproteínas/metabolismo , Apoproteínas/ultraestrutura , Arabidopsis/química , Arabidopsis/metabolismo , Arabidopsis/ultraestrutura , Proteínas de Arabidopsis/antagonistas & inibidores , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/ultraestrutura , Transporte Biológico/efeitos dos fármacos , Microscopia Crioeletrônica , Ácidos Indolacéticos/química , Ácidos Indolacéticos/metabolismo , Ftalimidas/química , Ftalimidas/farmacologia , Domínios Proteicos , Multimerização Proteica , Subunidades Proteicas/química , Subunidades Proteicas/metabolismo
2.
Proc Natl Acad Sci U S A ; 119(20): e2122063119, 2022 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-35533271

RESUMO

SignificanceThe chemical reduction of unsaturated bonds occurs by hydrogenation with H2 as the reductant. Conversely, in biology, the unavailability of H2 engenders the typical reduction of unsaturated bonds with electrons and protons from different cofactors, requiring olefin hydrogenation to occur by proton-coupled electron transfer (PCET). Moreover, the redox noninnocence of tetrapyrrole macrocycles furnishes unusual PCET intermediates, including the phlorin, which is an intermediate in tetrapyrrole ring reductions. Whereas the phlorin of a porphyrin is well established, the phlorin of a chlorin is enigmatic. By controlling the PCET reactivity of a chlorin, including the use of a hangman functionality to manage the proton transfer, the formation of a chlorinphlorin by PCET is realized, and the mechanism for its formation is defined.

3.
J Mol Cell Cardiol ; 186: 57-70, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37984156

RESUMO

BACKGROUND: Macrophage-derived foam cells are a hallmark of atherosclerosis. Scavenger receptors, including lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (OLR-1), are the principal receptors responsible for the uptake and modification of LDL, facilitating macrophage lipid load and the uptake of oxidized LDL by arterial wall cells. Krüppel-like factor 15 (KLF15) is a transcription factor that regulates the expression of genes by binding to the promoter during transcription. Therefore, this study aimed to investigate the precise role of macrophage KLF15 in atherogenesis. METHODS: We used two murine models of atherosclerosis: mice injected with an adeno-associated virus (AAV) encoding the Asp374-to-Tyr mutant version of human PCSK9, followed by 12 weeks on a high-fat diet (HFD), and ApoE-/-- mice on a HFD. We subsequently injected mice with AAV-KLF15 and AAV-LacZ to assess the role of KLF15 in the development of atherosclerosis in vivo. Oil Red O, H&E, and Masson's trichome staining were used to evaluate atherosclerotic lesions. Western blots and RT-qPCR were used to assess protein and mRNA levels, respectively. RESULTS: We determined that KLF15 expression was downregulated during atherosclerosis formation, and KLF15 overexpression prevented atherosclerosis progression. KLF15 expression levels did not affect body weight or serum lipid levels in mice. However, KLF15 overexpression in macrophages prevented foam cell formation by reducing OLR-1-meditated lipid uptake. KLF15 directly targeted and transcriptionally downregulated OLR-1 levels. Restoration of OLR-1 reversed the beneficial effects of KLF15 in atherosclerosis. CONCLUSION: Macrophage KLF15 transcriptionally downregulated OLR-1 expression to reduce lipid uptake, thereby preventing foam cell formation and atherosclerosis. Thus, our results suggest that KLF15 is a potential therapeutic target for atherosclerosis.


Assuntos
Aterosclerose , Células Espumosas , Humanos , Camundongos , Animais , Células Espumosas/metabolismo , Pró-Proteína Convertase 9/metabolismo , Macrófagos/metabolismo , Aterosclerose/patologia , Lipoproteínas LDL/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo
4.
J Am Chem Soc ; 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39377578

RESUMO

Oxygenation of hydrocarbons offers versatile catalytic routes to more valuable compounds, such as alcohols, aldehydes, and ketones. Despite the importance of monometallic copper-oxygen species as hydroxylating agents in biology, few synthetic model compounds are known to react with hydrocarbons, owing to high C-H bond dissociation energies. To overcome this challenge, the photoredox chemistry of monometallic copper (pyrazolyl)borate complexes coordinated by chlorate has been explored in the presence of C1-C6 alkanes with BDEs ≥ 93 kcal/mol. Ethane is photooxidized at room temperature under N2 with yields of 15-30%, which increases to 77% for the most oxidizing tris(3,5-trifluoromethyl-pyrazolyl)borate complex (Cu-3). This complex also promotes the photooxidation of methane to methanol in significant yield (38%) when the photoredox reaction is run under aerobic conditions. Ligand modification alters the reaction selectivity by tuning the redox potential. The ability to activate 1° C-H bonds of C1-C6 alkanes using visible light is consistent with the photogeneration of a powerfully oxidizing copper-oxyl, which is supported by photocrystallographic studies of the tris(3,4,5-tribromopyrazolyl)borate chlorate complex. Mechanistic studies are consistent with the hydrogen atom abstraction of the C-H bond by the copper-oxyl intermediate. We demonstrate for Cu-3 with hexane as an exemplar, that the photoredox chemistry may be achieved under solar conditions of one-sun illumination.

5.
J Am Chem Soc ; 146(37): 25578-25588, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39231366

RESUMO

Using a new hexanucleating anildophosphine ligand tBuLH3 (1,3,5-C6H9(NHC6H3-5-F-2-P(tBu)2)3), the all-monovalent [FeI3] compound (tBuL)Fe3 (1) was isolated and characterized by X-ray diffraction analysis, SQUID magnetometry, 57Fe Mössbauer spectroscopy, and cyclic voltammetry. The molecular structure of 1 reveals very close Fe-Fe distances of 2.3825(7), 2.4146(8), and 2.3913(8) Å which results in significant Fe-Fe interactions and a maximum high-spin S = 9/2 spin state as determined by SQUID magnetometry and further supported by quantum chemical calculations. Compound 1 mediates the multielectron, oxidative atom transfer from inorganic azide ([Bu4N][N3]), cyanate (Na[NCO]), and phosphonate (Na(dioxane)2.5[PCO]) to afford the [Fe3]-nitrido (N3-) and [Fe3]-phosphido (P3-) pnictides, (tBuL)Fe3(µ3-N) (2) and [(tBuL)Fe3(µ3-P)(CO)]- (3), respectively. Compounds 1-3 exhibit rich electrochemical behavior with three (for 1), four (for 2) and five (for 3) distinct redox events being observed in the cyclic voltammograms of these compounds. Finally, the all-monovalent 1 and the formally FeII/FeII/FeI compound 3, were investigated by alternating current (ac) SQUID magnetometry, revealing slow magnetic relaxation in both compounds, with 3 being found to be a unique example of a [Fe3]-phosphido single-molecule magnet having an energy barrier relaxation reversal of U = 30.7(6) cm-1 in the absence of an external magnetic field. This study demonstrates the utility of an all low-valent polynuclear cluster to perform multielectron redox chemistry and exemplifies the redox flexibility and unique physical properties that are present in the corresponding midvalent oxidation products.

6.
Genome Res ; 31(1): 40-50, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33334733

RESUMO

Mutations are the source of both genetic diversity and mutational load. However, the effects of increasing environmental temperature on plant mutation rates and relative impact on specific mutational classes (e.g., insertion/deletion [indel] vs. single nucleotide variant [SNV]) are unknown. This topic is important because of the poorly defined effects of anthropogenic global temperature rise on biological systems. Here, we show the impact of temperature increase on Arabidopsis thaliana mutation, studying whole genome profiles of mutation accumulation (MA) lineages grown for 11 successive generations at 29°C. Whereas growth of A. thaliana at standard temperature (ST; 23°C) is associated with a mutation rate of 7 × 10-9 base substitutions per site per generation, growth at stressful high temperature (HT; 29°C) is highly mutagenic, increasing the mutation rate to 12 × 10-9 SNV frequency is approximately two- to threefold higher at HT than at ST, and HT-growth causes an ∼19- to 23-fold increase in indel frequency, resulting in a disproportionate increase in indels (vs. SNVs). Most HT-induced indels are 1-2 bp in size and particularly affect homopolymeric or dinucleotide A or T stretch regions of the genome. HT-induced indels occur disproportionately in nucleosome-free regions, suggesting that much HT-induced mutational damage occurs during cell-cycle phases when genomic DNA is packaged into nucleosomes. We conclude that stressful experimental temperature increases accelerate plant mutation rates and particularly accelerate the rate of indel mutation. Increasing environmental temperatures are thus likely to have significant mutagenic consequences for plants growing in the wild and may, in particular, add detrimentally to mutational load.


Assuntos
Arabidopsis , Arabidopsis/genética , Biodiversidade , Mutação , Taxa de Mutação , Temperatura
7.
Plant Cell ; 33(12): 3658-3674, 2021 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-34524462

RESUMO

Protons (H+) in acidic soils arrest plant growth. However, the mechanisms by which plants optimize their biological processes to diminish the unfavorable effects of H+ stress remain largely unclear. Here, we showed that in the roots of Arabidopsis thaliana, the C2H2-type transcription factor STOP1 in the nucleus was enriched by low pH in a nitrate-independent manner, with the spatial expression pattern of NITRATE TRANSPORTER 1.1 (NRT1.1) established by low pH required the action of STOP1. Additionally, the nrt1.1 and stop1 mutants, as well as the nrt1.1 stop1 double mutant, had a similar hypersensitive phenotype to low pH, indicating that STOP1 and NRT1.1 function in the same pathway for H+ tolerance. Molecular assays revealed that STOP1 directly bound to the promoter of NRT1.1 to activate its transcription in response to low pH, thus upregulating its nitrate uptake. This action improved the nitrogen use efficiency (NUE) of plants and created a favorable rhizospheric pH for root growth by enhancing H+ depletion in the rhizosphere. Consequently, the constitutive expression of NRT1.1 in stop1 mutants abolished the hypersensitive phenotype to low pH. These results demonstrate that STOP1-NRT1.1 is a key module for plants to optimize NUE and ensure better plant growth in acidic media.


Assuntos
Proteínas de Transporte de Ânions/genética , Proteínas de Arabidopsis/genética , Arabidopsis/fisiologia , Nitratos/metabolismo , Proteínas de Plantas/genética , Rizosfera , Solo/química , Fatores de Transcrição/genética , Adaptação Fisiológica/genética , Proteínas de Transporte de Ânions/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Transporte Biológico , Concentração de Íons de Hidrogênio , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo
8.
Langmuir ; 40(6): 3248-3259, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38298055

RESUMO

Coalescence-induced jumping has promised a substantial reduction in the droplet detachment size and consequently shows great potential for heat-transfer enhancement in dropwise condensation. In this work, using molecular dynamics simulations, the evolution dynamics of the liquid bridge and the jumping velocity during coalescence-induced nanodroplet jumping under a perpendicular electric field are studied for the first time to further promote jumping. It is found that using a constant electric field, the jumping performance at the small intensity is weakened owing to the continuously decreased interfacial tension. There is a critical intensity above which the electric field can considerably enhance the stretching effect with a stronger liquid-bridge impact and, hence, improve the jumping performance. For canceling the inhibition effect of the interfacial tension under the condition of the weak electric field, a square-pulsed electric field with a paused electrical effect at the expansion stage of the liquid bridge is proposed and presents an efficient nanodroplet jumping even using the weak electric field.

9.
Langmuir ; 40(32): 17049-17059, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39083646

RESUMO

Reducing the contact time of droplet impacts on surfaces is crucial for various applications including corrosion prevention and anti-icing. This study aims to explore a novel strategy that greatly reduces contact time using a superhydrophobic mesh surface with multiple sets of mutually perpendicular ridges while minimizing the influence of the impacting location. The effects of the impact Weber numbers and ridge spacing on the characteristics of the impact dynamics and contact time are studied experimentally. The experimental results reveal that, for the droplet impact on mesh surfaces, ridges can segment the liquid film into independently multiple-retracting liquid subunits. The retracted subunits provide the upward driving force, which may promote the splashing or pancake bouncing of droplets. At this point, the contact time has a negligible sensitivity for the impacting position and is significantly reduced by up to 68%. Furthermore, the time, dynamic pressure, and energy criteria for triggering splashing and pancake bouncing are proposed theoretically. This work provides an understanding of the mechanism and the design guidelines for effectively reducing the contact time of the impacting droplet on superhydrophobic surfaces.

10.
Langmuir ; 40(20): 10759-10768, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38712734

RESUMO

Bouncing dynamics of a trailing drop off-center impacting a leading drop with varying time intervals and Weber numbers are investigated experimentally. Whether the trailing drop impacts during the spreading or receding process of the leading drop is determined by the time interval. For a short time interval of 0.15 ≤ Δt* ≤ 0.66, the trailing drop impacts during the spreading of the leading drop, and the drops completely coalesce and rebound; for a large time interval of 0.66 < Δt* ≤ 2.21, the trailing drop impacts during the receding process, and the drops partially coalesce and rebound. Whether the trailing drop directly impacts the surface or the liquid film of the leading drop is determined by the Weber number. The trailing drop impacts the surface directly at moderate Weber numbers of 16.22 ≤ We ≤ 45.42, while it impacts the liquid film at large Weber numbers of 45.42 < We ≤ 64.88. Intriguingly, when the trailing drop impacts the surface directly or the receding liquid film, the contact time increases linearly with the time interval but independent of the Weber number; when the trailing drop impacts the spreading liquid film, the contact time suddenly increases, showing that the force of the liquid film of the leading drop inhibits the receding of the trailing drop. Finally, a theoretical model of the contact time for the drops is established, which is suitable for different impact scenarios of the successive off-center impact. This study provides a quantitative relationship to calculate the contact time of drops successively impacting a superhydrophobic surface, facilitating the design of anti-icing surfaces.

11.
Int J Clin Pharmacol Ther ; 62(1): 1-7, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37969092

RESUMO

BACKGROUND: Failure to achieve target concentrations of ß-lactam antibiotics is not uncommon despite administration of high doses. The objective of this study was to identify risk factors predicting non-attainment of ß-lactams target concentration in critically ill patients receiving meropenem as an intravenous infusion. MATERIALS AND METHODS: The retrospective study included adult patients receiving meropenem by intravenous infusion and undergoing therapeutic drug monitoring (TDM) in the intensive care units (ICU) at Nanjing First Hospital. Blood samples were analyzed using UPLC-MS. Potential risk factors were evaluated by correlating them with meropenem trough concentrations (Cmin) lower than the targeted concentration (the minimum inhibitory concentration (MIC)). RESULTS: Non-attainment of target concentrations was observed in 41 patients (19.5%) of the 210 patients examined. Predictors for non-attainment using multivariate logistic regression analysis were: age (p = 0.013), dosage (p = 0.042), augmented renal clearance (ARC), (p = 0.041). CONCLUSION: In addition to the expected risk factors (age and dosage), ARC was a predictor for non-attainment of the target concentration. The risk of non-attainment of target concentrations increased with an increase in creatinine clearance. Attention should be given to ARC and creatinine clearance when administering meropenem by intravenous infusion.


Assuntos
Antibacterianos , Estado Terminal , Adulto , Humanos , Meropeném , Antibacterianos/efeitos adversos , Estado Terminal/terapia , Estudos Retrospectivos , Creatinina , Cromatografia Líquida , Espectrometria de Massas em Tandem
12.
Int J Clin Pharmacol Ther ; 62(4): 178-193, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38294244

RESUMO

OBJECTIVE: To investigate the nephroprotective potential of orally administered bracken Pteridium aquilinum extract against renal damage in quails, induced by a high-purine diet, to form a foundation for subsequent clinical studies and applications. MATERIALS AND METHODS: A mass spectrometry analysis was conducted on the pteridophyte subjected to steam explosion. Network pharmacological methods were then utilized to pinpoint shared targets and pathways, which suggested that Pteridium aquilinum has a capability to counteract renal injury. A total of 48 specific-pathogen-free (SPF) "Difaku" quails were selected and segregated into six distinct groups. The control group received a standard diet, whereas the other groups were fed a high-purine diet. Beginning on day 14, each group was subjected to designated therapeutic measures. The study continued for 40 days, after which relevant biological markers were assessed. RESULTS: Active compound peaks from the steam-exploded Pteridium aquilinum were isolated. Subsequently, 101 targets and several pathways associated with renoprotective effects were discerned, indicating that the Pteridium aquilinum achieves its nephroprotective function through comprehensive regulatory mechanisms. The high-purine diet successfully induced hyperuricemia in the quails, resulting in renal impairment. Following intervention with varied Pteridium aquilinum dosages, renal protective outcomes were evident, though xanthine oxidase activity remained unaffected. Histological analyses demonstrated a notable decrease in renal lesion dimensions post-intervention. CONCLUSION: The steam-exploded bracken Pteridium aquilinum may provide nephroprotective benefits against hyperuricemia-induced renal damage in quails through comprehensive regulatory processes. This highlights the Pteridium aquilinum's potential as an innovative nephroprotective therapeutic and dietary solution, presenting a promising avenue for hyperuricemia and renal damage treatment and prevention.


Assuntos
Hiperuricemia , Pteridium , Animais , Humanos , Pteridium/química , Codorniz , Hiperuricemia/tratamento farmacológico , Hiperuricemia/prevenção & controle , Farmacologia em Rede , Vapor , Rim , Purinas
13.
J Integr Plant Biol ; 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39092784

RESUMO

Calcium (Ca) is essential for plant growth and stress adaptation, yet its availability is often limited in acidic soils, posing a major threat to crop production. Understanding the intricate mechanisms orchestrating plant adaptation to Ca deficiency remains elusive. Here, we show that the Ca deficiency-enhanced nuclear accumulation of the transcription factor SENSITIVE TO PROTON RHIZOTOXICITY 1 (STOP1) in Arabidopsis thaliana confers tolerance to Ca deprivation, with the global transcriptional responses triggered by Ca deprivation largely impaired in the stop1 mutant. Notably, STOP1 activates the Ca deprivation-induced expression of CATION/Ca2+ EXCHANGER 1 (CCX1) by directly binding to its promoter region, which facilitates Ca2+ efflux from endoplasmic reticulum to cytosol to maintain Ca homeostasis. Consequently, the constitutive expression of CCX1 in the stop1 mutant partially rescues the Ca deficiency phenotype by increasing Ca content in the shoots. These findings uncover the pivotal role of the STOP1-CCX1 axis in plant adaptation to low Ca, offering alternative manipulating strategies to improve plant Ca nutrition in acidic soils and extending our understanding of the multifaceted role of STOP1.

14.
Angew Chem Int Ed Engl ; 63(24): e202403263, 2024 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-38657031

RESUMO

Hierarchical self-assembly represents a powerful strategy for the fabrication of functional materials across various length scales. However, achieving precise formation of functional hierarchical assemblies remains a significant challenge and requires a profound understanding of molecular assembly interactions. In this study, we present a molecular-level understanding of the hierarchical assembly of sequence-defined peptoids into multidimensional functional materials, including twisted nanotube bundles serving as a highly efficient artificial light harvesting system. By employing synchrotron-based powder X-ray diffraction and analyzing single crystal structures of model compounds, we elucidated the molecular packing and mechanisms underlying the assembly of peptoids into multidimensional nanostructures. Our findings demonstrate that incorporating aromatic functional groups, such as tetraphenyl ethylene (TPE), at the termini of assembling peptoid sequences promotes the formation of twisted bundles of nanotubes and nanosheets, thus enabling the creation of a highly efficient artificial light harvesting system. This research exemplifies the potential of leveraging sequence-defined synthetic polymers to translate microscopic molecular structures into macroscopic assemblies. It holds promise for the development of functional materials with precisely controlled hierarchical structures and designed functions.


Assuntos
Peptoides , Peptoides/química , Peptoides/síntese química , Nanoestruturas/química , Nanotubos/química , Modelos Moleculares , Tamanho da Partícula
15.
J Am Chem Soc ; 145(16): 9304-9312, 2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37043219

RESUMO

Atomically precise metal nanoclusters (NCs) are an intriguing class of crystalline solids with unique physicochemical properties derived from tunable structures and compositions. Most atomically precise NCs require closed-shells and coordinatively saturated surface metals in order to be stable. Herein, we report Au43(C≡CtBu)20 and Au42Ag1(C≡CtBu)20, which feature open electronic and geometric shells, leading to both paramagnetism (23 valence e-) and enhanced catalytic activity from a single coordinatively unsaturated surface metal. The Au-alkynyl surface motifs of these NCs form five helical stripes around the inner Au12 kernel, imparting chirality and high thermal stability. Density functional theory (DFT) calculations suggest that there are minimal energy differences between the open-shelled NCs and hypothetical closed-shell systems and that the open-shelled electronic configuration gives rise to the largest band gap, which is known to promote cluster stability. Furthermore, we highlight how coordinatively unsaturated surface metals create active sites for the catalytic oxidation of benzyl alcohol to benzaldehyde, leading to high selectivity and increased conversion. This work represents the first example of an atomically precise Au NC with a double open-shelled structure and provides a promising platform for investigating the magnetic and catalytic properties of noble metal nanoparticles.

16.
J Am Chem Soc ; 145(42): 23361-23371, 2023 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-37844297

RESUMO

Molecular recognition lies at the heart of biological functions, which inspires lasting research in artificial host syntheses to mimic biomolecules that can recognize, process, and transport molecules with the highest level of complexity; nonetheless, the design principle and quantifying methodology of artificial hosts for multiple guests (≥4) remain a formidable task. Herein, we report two rhombic dodecahedral cages [(Zn/Fe)8Pd6-MOC-16], which embrace 12 adaptive pockets for multiguest binding with distinct conformational dynamics inherent in metal-center lability and are able to capture 4-24 guests to manifest a surprising complexity of binding scenarios. The exceptional high-order and hierarchical encapsulation phenomena suggest a wide host-guest dynamic-fit, enabling conformational adjustment and adaptation beyond the duality of induced-fit and conformational selection in protein interactions. A critical inspection of the host-guest binding events in solution has been performed by NMR and ESI-MS spectra, highlighting the importance of acquiring a reliable binding repertoire from different techniques and the uncertainty of quantifying the binding affinities of multiplying guests by an oversimplified method.


Assuntos
Biomimética , Conformação Molecular
17.
Ann Surg Oncol ; 30(4): 2242-2243, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36581725

RESUMO

The past eighth edition of the American Joint Committee on Cancer (AJCC)/International Union against Cancer (UICC) pathologic tumor-node-metastasis (pTNM) staging system for esophageal squamous cell carcinoma (ESCC) patients, which also is the gold standard of postoperative treatment decision-making, needs to be continuously improved. To improve the efficiency of the staging system, the proteomic data from Chinese ESCC patients was combined with preoperative radiomic data and pTNM data to establish the multiomic RadpTNM and ProtRadpTNM models and compare them with the traditional pTNM staging system. The results suggest that both the RadpTNM and ProtRadpTNM models are significantly better than the traditional pTNM staging system. Future prospective multicentered cohort studies in Asian and Caucasian patients with ESCC are warranted to evaluate the efficiency of the multiomic models.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/cirurgia , Carcinoma de Células Escamosas do Esôfago/patologia , Prognóstico , Estadiamento de Neoplasias , Neoplasias Esofágicas/patologia , Multiômica , Proteômica , Estudos Retrospectivos
18.
Ann Surg Oncol ; 30(4): 2227-2241, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36587172

RESUMO

OBJECTIVE: This study aimed to construct a new staging system for patients with esophageal squamous cell carcinoma (ESCC) based on combined pathological TNM (pTNM) stage, radiomics, and proteomics. METHODS: This study collected patients with radiomics and pTNM stage (Cohort 1, n = 786), among whom 103 patients also had proteomic data (Cohort 2, n = 103). The Cox regression model with the least absolute shrinkage and selection operator, and the Cox proportional hazards model were used to construct a nomogram and predictive models. Concordance index (C-index) and the integrated area under the time-dependent receiver operating characteristic (ROC) curve (IAUC) were used to evaluate the predictive models. The corresponding staging systems were further assessed using Kaplan-Meier survival curves. RESULTS: For Cohort 1, the RadpTNM4c staging systems, constructed based on combined pTNM stage and radiomic features, outperformed the pTNM4c stage in both the training dataset 1 (Train1; IAUC 0.711 vs. 0.706, p < 0.001) and the validation dataset 1 (Valid1; IAUC 0.695 vs. 0.659, p < 0.001; C-index 0.703 vs. 0.674, p = 0.029). For Cohort 2, the ProtRadpTNM2c staging system, constructed based on combined pTNM stage, radiomics, and proteomics, outperformed the pTNM2c stage in both the Train2 (IAUC 0.777 vs. 0.610, p < 0.001; C-index 0.898 vs. 0.608, p < 0.001) and Valid2 (IAUC 0.746 vs. 0.608, p < 0.001; C-index 0.889 vs. 0.641, p = 0.009) datasets. CONCLUSIONS: The ProtRadpTNM2c staging system, based on combined pTNM stage, radiomic, and proteomic features, improves the predictive performance of the classical pTNM staging system.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/diagnóstico por imagem , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/patologia , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patologia , Proteômica , Estadiamento de Neoplasias , Nomogramas
19.
Langmuir ; 39(37): 13371-13385, 2023 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-37675482

RESUMO

Profiting from their slippery nature, lubricant-infused porous surfaces endow with droplets excellent mobility and consequently promise remarkable heat transfer improvement for dropwise condensation. To be a four-phase wetting system, the droplet wettability configurations and the corresponding dynamic characteristics on lubricant-infused porous surfaces are closely related to many factors, such as multiple interfacial interactions, surface features, and lubricant thickness, which keeps a long-standing challenge to promulgate the underlying physics. In this work, thermodynamically theoretical analysis and three-dimensional molecular dynamics simulations with the coarse-grained water and hexane models are carried out to explore droplet wettability and mobility on lubricant-infused porous surfaces. Combined with accessible theoretical criteria, phase diagrams of droplet configurations are constructed with a comprehensive consideration of interfacial interactions, surface structures, and lubricant thickness. Subsequently, droplet sliding and coalescence dynamics are quantitatively defined under different configurations. Finally, in terms of the promotion of dropwise condensation, a non-cloaking configuration with the encapsulated state underneath the droplet is recommended to achieve high droplet mobility owing to the low viscous drag of the lubricant and the eliminated pinning effect of the contact line. On the basis of the low oil-water and water-solid interactions, a stable lubricant layer with a relatively low thickness is suggested to construct slippery surfaces.

20.
Langmuir ; 39(45): 16023-16034, 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37916520

RESUMO

Extensive research has shown that a superhydrophobic cylindrical substrate could lead to a noncircumferential symmetry of an impacting droplet, reducing the contact time accordingly. It is of practical significance in applications, such as anti-icing, anticorrosion, and antifogging. However, few accounts have adequately addressed the off-centered impact of the droplet, despite it being more common in practice. This work investigates the dynamic behavior of a droplet off-centered impacting a superhydrophobic cylinder via the lattice Boltzmann method. The effect of the off-centered distance is primarily discussed for droplets taking various Weber numbers and cylinder sizes. The results show that the imposition of an off-center distance can further disrupt the droplet symmetry during the impact. As the off-center distance increases, the droplet movement is gradually tilted toward the offset side until it tangentially passes the cylinder side, resulting in a direct dripping mode. The dynamic features, focusing mainly on maximum spreading in the axial direction and contact time, are specifically explored. A quantitative model of the maximum spreading factor is proposed based on the equivalent transformation from the off-center impact into oblique hitting, considering the full range of off-centered distance. A preliminary contact time model is established for droplet off-centered impacting superhydrophobic cylinders by substituting the maximum spreading and the effective velocity of the liquid moving. This work aims to make an original contribution to the fundamental knowledge of droplet impact and could be of value for related applications.

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