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INTRODUCTION: Divided narratives pose long-standing difficulties in physician and patient communication. In decision-making on cancer treatment, divided narratives between physicians and patients hinder mutual understanding and agreement over the illness and its treatment. For effective decision-making on treatments, it is necessary to investigate the similarities and differences in these divided narratives. METHODS: This study adopted a qualitative research design of narrative inquiry to examine the data, which included interviews with 32 cancer patients and 16 paired physicians in two hospitals in China. Data analysis was conducted using grounded theory to generate findings. RESULTS: Both physicians and patients were concerned about goals and obstacles to their decision-making on cancer treatment. Four common aspects of goal setting were identified from the divided narratives: decision pools, treatment goals, identity practice and preferred identity. Four common obstacles were identified: pains and trust, communication gap, financial issues and complex family. However, the meanings attached to these eight aspects differed between physicians and patients. CONCLUSION: Cancer treatment decision-making is an encounter of the scientific world and lifeworld. A divided narrative approach can identify the similarities and differences in the decision-making on cancer treatment between physicians and patients. Physicians generally adopt a rational decision-making approach, whereas patients generally adopt a relational decision-making approach. Despite the common concerns in their goals and obstacles, physicians and patients differed in their contextualized interpretations, which demonstrates the physicians' and the patients' pursuit of preferred identities in decision-making. The results of this study provide a new perspective to treatment decision-making, emphasizing the importance of narrative integration in reaching mutual agreement. PATIENT AND PUBLIC CONTRIBUTION: The findings were shared with 15 cancer patients and caregivers for feedback and advice in June 2024. This study was also presented at the international conferences of COMET (International and Interdisciplinary Conference on Communication, Medicine, and Ethics) and ICCH (International Conference on Communication in Healthcare) 2023 for continuous feedback and comments.
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Comunicación , Toma de Decisiones , Neoplasias , Relaciones Médico-Paciente , Médicos , Investigación Cualitativa , Humanos , Neoplasias/terapia , Neoplasias/psicología , Femenino , Masculino , Persona de Mediana Edad , China , Adulto , Médicos/psicología , Narración , Entrevistas como Asunto , Teoría Fundamentada , AncianoRESUMEN
DNA-encoded library (DEL) technology is an effective method for small molecule drug discovery, enabling high-throughput screening against target proteins. While DEL screening produces extensive data, it can reveal complex patterns not easily recognized by human analysis. Lead compounds from DEL screens often have higher molecular weights, posing challenges for drug development. This study refines traditional DELs by integrating alternative techniques like photocross-linking screening to enhance chemical diversity. Combining these methods improved predictive performance for small molecule identification models. Using this approach, we predicted active small molecules for BRD4 and p300, achieving hit rates of 26.7 and 35.7%. Notably, the identified compounds exhibit smaller molecular weights and better modification potential compared to traditional DEL molecules. This research demonstrates the synergy between DEL and AI technologies, enhancing drug discovery.
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The sequestration of soil inorganic carbon (SIC) especially pedogenic carbonate (PC) is one of the important pathways reducing the concentration of atmospheric carbon dioxide and thus mitigating climate change in coastal areas. Using the technology of 13C stable isotope, we analyzed the differences in the composition and storage of SIC, and explored the key physicochemical properties influencing soil PC storage in different horizons (0-10, 11-20, 21-40, 41-60, 61-80 and 81-100 cm) from Suaeda salsa wetland (SS), Spartina alterniflora wetland (SA), young poplar plantation (YP), and mature poplar plantation (MP) in coastal area of the northern Jiangsu Province. The results showed that except for the surface (0-10 cm) soil in MP, the SIC content was higher than SOC in all soil horizons. Overall, neither the soil PC to SIC ratio nor the SIC storage were significantly different in SA and SS soils. Compared to wetland soils (0-40 cm), the soil PC to SIC ratio was reduced by 32.7% and 54.1% and the PC storage was reduced by 40.5% and 59.2%, the lithogenic carbonate (LC) storage changed little, while the SIC storage was reduced by 21.0% and 17.9%, respectively in the YP and MP soils. Compared to the YP soils (0-100 cm), both the soil PC to SIC ratio and the PC storage were significantly reduced while the LC storage was significantly increased, especially at the 41-100 cm soil horizons, meanwhile, the SIC storage was not significantly changed in the MP soils. Results of the structural equation modeling (SEM) indicated that key factors influencing soil PC storage were the ratio of PC to SIC, followed by the SOC content and bulk density. SOC could inhibit the formation of soil PC. Generally, the coastal wetlands have greater SIC storage and sequestration potential than poplar plantations, and the PC sequestration can be regulated by modulating the ratio of PC to SIC and SOC content.
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Carbono , Suelo , Humedales , Suelo/química , China , Carbono/análisis , Carbono/química , Populus/química , Populus/crecimiento & desarrollo , Secuestro de Carbono , Carbonatos/análisis , Carbonatos/química , Océanos y Mares , Poaceae/crecimiento & desarrollo , Poaceae/química , Ecosistema , Cambio ClimáticoRESUMEN
Aqueous-phase reforming of methanol represents a promising avenue for hydrogen (H2) production. However, developing highly efficient and low-cost nonprecious catalysts remains challenging. Here, we report the synthesis of Cu-based catalysts with Cu, Cu2O, and CuN3 nanoparticles anchored on the nitrogen-doped carbon, forming Cu0/Cu+/Cu-N3 active sites. This catalyst achieves a H2 production rate of 140.1 µmol/gcat/s at 210 °C, which is several times to 2 orders of magnitude higher than that of Cu-, Ni-, even Pt-based catalysts, demonstrating excellent long-term stability over 350 h at 210 °C. A mechanism investigation reveals that the Cu-N3 site facilitates water dissociation into *OH and improves *CO and *OH conversion, leading to enhanced CO conversion and H2 production kinetics.
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In cold regions with high daily temperature gradients (>20 °C), the durability of cement-stabilized macadam (CSM) base materials is poor and prone to cracking. To effectively reduce the cracking of semi-rigid base layers in cold regions with high daily temperature gradients and extend fatigue life, this study focused on cracking and fatigue characteristics of CSM with a 10% commercial early strength agent (ESA) added by the external mixing method under different curing conditions. The ESA was manufactured by Jiangsu Subote New Materials Co., Ltd. (Nanjing, China). The curing conditions were divided into variable temperature (0-20 °C) and standard temperature (20 °C). CSM curing was carried out through a programmable curing box. The research results indicated that the variable temperature curing conditions reduced the strength and fatigue resistance of CSM and accelerated the modulus attenuation rate of CSM. At the same time, the drying shrinkage of CSM was greater. The temperature shrinkage coefficient and strain of CSM under variable temperature conditions were smaller than those under standard temperature conditions. The effect of variable temperature conditions on the cracking and durability of CSM could not be ignored in cold regions. Compared to standard temperature curing conditions, the indirect tensile strength of CSM reduced by 31.04% under variable temperature conditions, the coefficient of variation increased by 2.97 times, and the discrete type significantly increased. Compared with CSM without ESA, the dry and temperature shrinkage strains of CSM with 10% ESA were reduced by 24.65% and 26.10%, respectively. At a stress level of 0.6, compared to standard temperature curing conditions, the fatigue life of CSM decreased by 97.19% under variable temperature conditions. Under variable temperature conditions, the fatigue life of CSM with 10% ESA increased by 196 times compared to 0% ESA. Adding ESA enhanced the anti-shrinkage cracking, strength, and durability of CSM under variable temperatures. ESA incorporation effectively compensated for the weakened characteristics of CSM under variable temperature conditions. The study proposed a practical approach for boosting the durability of CSM in cold environments.
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The DNA-encoded library (DEL) is a robust tool for chemical biology and drug discovery. In this study, we developed a DNA-compatible light-promoted reaction that is highly efficient and plate-compatible for DEL construction based on the formation of the indazolone scaffold. Employing this high-efficiency approach, we constructed a DEL featuring an indazolone core, which enabled the identification of a novel series of ligands specifically targeting E1A-binding protein (p300) after DEL selection. Taken together, our findings underscore the feasibility of light-promoted reactions in DEL synthesis and unveil promising avenues for developing p300-targeting inhibitors.
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ADN , Descubrimiento de Drogas , Proteína p300 Asociada a E1A , Indazoles , Bibliotecas de Moléculas Pequeñas , ADN/química , Indazoles/química , Indazoles/farmacología , Proteína p300 Asociada a E1A/antagonistas & inhibidores , Proteína p300 Asociada a E1A/metabolismo , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/farmacología , Descubrimiento de Drogas/métodos , Humanos , Biblioteca de Genes , LigandosRESUMEN
The proton therapy system has significant clinical advantages over traditional tumor radiation treatment equipment and is also far more complex in terms of system architecture. However, due to the large size and complexity of these devices, electromagnetic compatibility testing faces considerable challenges. To address these challenges, this paper studies the electromagnetic characteristics and working principles of various components in the proton therapy system, combines them with corresponding standard requirements, and delves into the difficulties and testing methods of electromagnetic compatibility immunity detection through actual repeated tests. Furthermore, the paper proposes testing key points for beam quality tests and provides references for the selection of emission sources and distance settings in radio frequency electromagnetic field radiation immunity testing. The paper also supplements and improves the descriptions of alternative methods in the standards and offers solutions and testing suggestions for issues such as the excessive thickness of cables in the proton therapy system and the lack of suitable fixtures in conducted anti-interference tests. The provision of these solutions offers more effective references for related staff during testing, helps address difficulties encountered in practical operations, and thus more effectively ensures the safety and effectiveness of proton therapy systems.
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Terapia de Protones , Campos Electromagnéticos , Humanos , Fenómenos ElectromagnéticosRESUMEN
Sediment-derived dissolved organic matter (SDOM) is instrumental in the cycling of nutrients and heavy metals within lakes, influencing ecological balance and contaminant distribution. Given the influence of photodegradation on the alteration and breakdown of SDOM, further understanding of this process is essential. In this research, the properties of the SDOM photodegradation process and its metal-binding reactions in Nansi Lake were analyzed using the EEM-PARAFAC and 2D-SF/FTIR-COS techniques. Our study identified three sorts of humic-like components and one protein-like component in SDOM, with the humic-like material accounting for 71.3 ± 5.19% of the fluorescence intensity (Fmax). Photodegradation altered the abundance and structure of SDOM, with a 41.6 ± 5.82% decrease in a280 and a 29.1 ± 9.31% reduction in Fmax after 7 days, notably reducing the protein-like component C4 by 54.0 ± 5.17% and the humic-like component C2 by 48.5 ± 2.54%, which led to SDOM being formed with lower molecular weight and aromaticity. After photodegradation, the LogKCu values for humic-like and protein-like substances decreased (humic-like C2: LogKCu: 1.35 ± 0.10-1.11 ± 0.15, protein-like C4: 1.49 ± 0.14-1.29 ± 0.34), yet the preferential binding sequence of protein-like materials and specific functional groups with Cu2+ such as aliphatic C-OH, amide (I) C=O and polysaccharide C-O groups remained unaltered. Our results enhance the knowledge of light-induced SDOM alterations and offer insights into SDOM-metal interactions in aquatic ecosystems.
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Sedimentos Geológicos , Lagos , Fotólisis , Contaminantes Químicos del Agua , Lagos/química , China , Sedimentos Geológicos/química , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/análisis , Sustancias Húmicas/análisis , Compuestos Orgánicos/química , Metales/química , Monitoreo del Ambiente/métodosRESUMEN
Inspired by previous selection outcomes, we investigated and developed a rhodium-promoted C-H activation/annulation reaction of DNA-linked terminal alkynes and aromatic acids. This reaction exhibits excellent efficiency with high conversions and a broad substrate scope. Most importantly, the unique DEL-compatible conditions provide a better scenario for yielding an isocoumarin scaffold compared to conventional organic reaction conditions, and this newly developed on-DNA method has confirmed its feasibility in preparing DNA-encoded libraries.
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Alquinos , ADN , Rodio , Rodio/química , Alquinos/química , Estructura Molecular , ADN/química , Catálisis , Isocumarinas/química , Isocumarinas/síntesis químicaRESUMEN
The objective of this research is to enhance the high-temperature antirutting and antiaging characteristics of bioasphalt. In this study, silica fume (SF) was selected to modify bioasphalt. The dosage of bio-oil in bioasphalt was 5%, and the dosage of SF was 2%, 4%, 6%, 8%, and 10% of bioasphalt. The high- and low-temperature characteristics, aging resistance, and temperature sensitivity of Bio + SF were evaluated by temperature sweep (TS), the multiple stress creep recovery (MSCR) test, the bending beam rheology (BBR) test, and the viscosity test. Meanwhile, the road behavior of the Bio + SF mixture was evaluated using the rutting test, low-temperature bending beam test, freeze-thaw splitting test, and fatigue test. The experimental results showed that the dosage of SF could enhance the high-temperature rutting resistance, aging resistance, and temperature stability of bioasphalt. The higher the dosage of SF, the more significant the enhancement effect. However, incorporating SF weakened bioasphalt's low-temperature cracking resistance properties. When the SF dosage was less than 8%, the low-temperature cracking resistance of Bio + SF was still superior to that of matrix asphalt. Compared with matrix asphalt mixtures, the dynamic stability, destructive strain, freeze-thaw splitting strength ratio, and fatigue life of 5%Bio + 8%SF mixtures increased by 38.4%, 49.1%, 5.9%, and 68.9%, respectively. This study demonstrates that the development of SF-modified bioasphalt could meet the technical requirements of highway engineering. Using SF and bio-oil could decrease the consumption of natural resources and positively reduce environmental pollution.
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DNA-encoded library (DEL) technology is gaining attention for its rapid construction and deconvolution capabilities. Our study explored a novel strategy using rational DELs tailored for the SARS-CoV-2 papain-like protease, which revealed new fragments. Structural changes post-DEL screening mimic traditional medicinal chemistry lead optimization. We unveiled unique aromatic structures offering an alternative optimization path. Notably, we identified superior binding fragments targeting the BL2 groove. Derivative 16 emerged as the most promising by exhibiting IC50 values of 0.25 µM. Derivative 6, which features an aromatic fragment capped with a naphthalene moiety, showed IC50 values of 2.91 µM. Molecular modeling revealed hydrogen bond interactions with Lys157 residue and potential covalent interactions with nearby amino acid residues. This research underscored DEL's potential for fragment-based drug discovery against SARS-CoV-2 protease.
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Millions of women worldwide are infertile due to gynecological disorders, including premature ovarian insufficiency, polycystic ovary syndrome, Asherman syndrome, endometrial atrophy, and fallopian tube obstruction. These conditions frequently lead to infertility and have a substantial impact on the quality of life of the affected couples, primarily because of their psychological implications and high financial costs. Recently, using platelets to stimulate cell proliferation and tissue differentiation has emerged as a promising approach in regenerative medicine. Platelet-rich plasma (PRP) shows considerable potential for promoting endometrial hypertrophy and follicle development, making it a promising therapeutic option for tissue repair or replacement. This review provides an overview of the recent advancements and underlying mechanisms of PRP therapy for various female reproductive diseases and presents new therapeutic options for addressing female infertility.
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Infertilidad Femenina , Plasma Rico en Plaquetas , Humanos , Femenino , Infertilidad Femenina/terapia , Enfermedades del Sistema Endocrino/terapia , Enfermedades de los Genitales Femeninos/terapia , AnimalesRESUMEN
It is an urgent need to tackle the global crisis of multidrug-resistant bacterial infections. We report here an innovative strategy for large-scale screening of new antibacterial agents using a whole bacteria-based DNA-encoded library (DEL) of vancomycin derivatives via peripheral modifications. A bacterial binding affinity assay was established to select the modification fragments in high-affinity compounds. The optimal resynthesized derivatives demonstrated excellently enhanced activity against various resistant bacterial strains and provided useful structures for vancomycin derivatization. This work presents the new concept in a natural product-templated DEL and in antibiotic discovery through bacterial affinity screening, which promotes the fight against drug-resistant bacteria.
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Antibacterianos , Vancomicina , Vancomicina/farmacología , Vancomicina/química , Antibacterianos/química , Bacterias/metabolismo , Farmacorresistencia Bacteriana Múltiple , ADN , Pruebas de Sensibilidad MicrobianaRESUMEN
Cardiovascular diseases (CVDs) are the leading cause of death and disability worldwide. It is essential to develop novel interventions to prevent/delay CVDs by targeting their fundamental cellular and molecular processes. Melatonin is a small indole molecule acting both as a hormone of the pineal gland and as a local regulator molecule in various tissues. It has multiple features that may contribute to its cardiovascular protection. Moreover, melatonin enters all cells and subcellular compartments and crosses morphophysiological barriers. Additionally, this indoleamine also serves as a safe exogenous therapeutic agent. Increasing evidence has demonstrated the beneficial effects of melatonin in preventing and improving cardiovascular risk factors. Exogenous administration of melatonin, as a result of its antioxidant and anti-inflammatory properties, has been reported to decrease blood pressure, protect against atherosclerosis, attenuate molecular and cellular damage resulting from cardiac ischemia/reperfusion, and improve the prognosis of myocardial infarction and heart failure. This review aims to summarize the beneficial effects of melatonin against these conditions, the possible protective mechanisms of melatonin, and its potential clinical applicability in CVDs.
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Enfermedades Cardiovasculares , Melatonina , Infarto del Miocardio , Humanos , Melatonina/farmacología , Melatonina/fisiología , Melatonina/uso terapéutico , Enfermedades Cardiovasculares/tratamiento farmacológico , Antioxidantes , Isquemia/tratamiento farmacológico , Infarto del Miocardio/tratamiento farmacológicoRESUMEN
The anaerobic treatment of sulfide-containing organic wastewater (SCOW) is significantly affected by pH, causing dramatic decrease of treatment efficiency when pH deviates from its appropriate range. Fe0 has proved as an effective strategy on mitigating the impact of pH. However, systematic analysis of the influence mechanism is still lacking. To fill this gap, the impact of different initial pH values on anaerobic treatment efficiency of SCOW with Fe0 addition, the change of fermentation type and methanogens, and intra-extracellular electron transfer were explored in this study. The results showed that Fe0 addition enhanced the efficacy of anaerobic treatment of SCOW at adjusted initial pH values, especially at pH 6. Mechanism analysis showed that respiratory chain-related enzymes and electron shuttle secretion and resistance reduction were stimulated by soluble iron ions generated by Fe0 at pH 6, which accelerated intra-extracellular electron transfer of microorganisms, and ultimately alleviated the impact of acidic pH on the system. While at pH 8, Fe0 addition increased the acetogenic bacteria abundance, as well as optimized the fermentation type and improved the F420 coenzyme activity, resulting in the enhancement of treatment efficiency in the anaerobic system and remission of the effect of alkaline pH on the system. At the neutral pH, Fe0 addition had both advantages as stimulating the secretion of respiratory chain and electron transfer-related enzymes at pH 6 and optimizing the fermentation type pH 8, and thus enhanced the treatment efficacy. This study provides important insights and scientific basis for the application of new SCOW treatment technologies.
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Sulfatos , Aguas Residuales , Anaerobiosis , Reactores Biológicos , Sulfuros , Concentración de Iones de Hidrógeno , Aguas del Alcantarillado/microbiologíaRESUMEN
The DNA-encoded library (DEL) is a powerful hit generation tool for chemical biology and drug discovery; however, the optimization of DEL hits remained a daunting challenge for the medicinal chemistry community. In this study, hit compounds targeting the WIN binding domain of WDR5 were discovered by the initial three-cycle linear DEL selection, and their potency was further enhanced by a cascade DEL selection from the focused DEL designed based on the original first run DEL hits. As expected, these new compounds from the second run of focused DEL were more potent WDR5 inhibitors in the protein binding assay confirmed by the off-DNA synthesis. Interestingly, selected inhibitors exhibited good antiproliferative activity in two human acute leukemia cell lines. Taken together, this new cascade DEL selection strategy may have tremendous potential for finding high-affinity leads against WDR5 and provide opportunities to explore and optimize inhibitors for other targets.
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ADN , Descubrimiento de Drogas , Humanos , Biblioteca de Genes , Unión Proteica , ADN/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismoRESUMEN
Environmental indicators at different scales are important for environmental management, daily life, and scientific research. Because of the lack of statistics below a national scale for many environmental indicators, scholars have developed various downscaling methods to obtain finer-scale and diverse forms of data for different environmental indicators. However, the existing downscaling methods for environmental indicators are diverse and fragmented. Here, we reviewed the downscaling methods by reclassifying the environmental indicators from a life cycle perspective into five categories: natural resources use and related attributes; material and energy consumption; environmental discharge; climate change; and environmental footprints. We first provide a general introduction to downscaling theory in the environmental field, including definitions, techniques, and evolution. We then elaborate on downscaling methods and make an inventory of the five categories of environmental indicators. We summarize the downscaling methods commonly applied to specific indicators, scale transformation, the strengths and limitations of corresponding methods, and provide specific examples. Next, we discuss ways to select or construct downscaling methods based on four principles: objective orientation, data accessibility, model feasibility, and model adjustment. Finally, we explore the future direction of downscaling and provide insights for improving downscaling for environmental indicators. In this review, we generalize and clarify the downscaling techniques for environmental indicators, which will help facilitate the appropriate selection of downscaling methods by researchers.
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The development of efficient adsorbents for heavy metal pollution, especially five toxic heavy metals, has attracted great research interest. Polymer-based adsorbents have aroused research value for their abundant functional groups and high porosity to the ability to capture metal ions. We designed a sulfhydryl-functionalized polymer microcomposite to take up Cr(VI), As(III), Cd(II), and Pb(II). The adsorption capacity achieved was 64.2 mg g-1 for Cr(VI), 44.9 mg g-1 for As(III), 35.5 mg g-1 for Cd(II), and 18.2 mg g-1 for Pb(II). Langmuir and Sips isotherm model is dominant for As(III), Cd(II), and Pb(II) adsorption. Pseudo-second-order kinetic models can better describe the adsorption behavior of Cr(VI), implying that chemisorption is accompanied by Cr(VI) adsorption. Cr(VI) simultaneous reduction to Cr(III) through the benzenoid amine oxidate pathway was the dominant mechanism, precipitation for Cd(II) adsorption was convinced, and chelation between As(III)/Pb(II) andâSH group and complexation between Pb(II) and CâO or benzene hydroxyl were a plausible mechanism for As(III) and Pb(II) adsorption.