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As a promising liquid biopsy biomarker, exosomes have demonstrated great potential and advantages in the noninvasive tumor diagnosis. However, an accurate and sensitive method for tumors-associated exosomes detection is scarce. Herein, we presented an easy-operation aptasensor which simultaneously detect multiple exosomal proteins by using multicolor fluorescent DNA nanoassemblies (FDNs) and CD63 aptamer-modified magnetic beads (MNPs-AptCD63). In this system, the FDNs were firstly constructed by encapsulating different quantum dots (QDs) into rolling circle amplification (RCA) products that contained different aptamer sequences. Thus, the FDNs could selectively recognize the different exosomal proteins captured by the MNPs-AptCD63, and achieve the multiplex and sensitive detection according to the fluorescence of QDs. Benefiting from the signal amplification capacity and high selectivity of FDNs, this aptasensor not only could detect exosomes as low as 650 particles/µL, but also showed accurate analysis in clinical samples. In addition, we can also achieve point-of-care testing (POCT) due to the simple analysis steps and naked-eye observable fluorescence of QDs under the ultraviolet irradiation. We believe that our aptasensor could provide a promising platform for exosomes-based personalized diagnosis and precise monitoring of human health.

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De novo purine synthesis metabolism plays a crucial role in tumor cell survival and malignant progression. However, the specific impact of this metabolic pathway on chemoresistance in ovarian cancer remains unclear. This study aims to elucidate the influence of de novo purine synthesis on chemoresistance in ovarian cancer and its underlying regulatory mechanisms. We analyzed metabolic differences between chemosensitive and chemoresistant ovarian cancer tissues using mass spectrometry-based metabolomics. Cell growth, metabolism, chemoresistance, and DNA damage repair characteristics were assessed in vitro using cell line models. Tumor growth and chemoresistance were assessed in vivo using ovarian cancer xenograft tumors. Intervention of purines and NEK6-mediated purine metabolism on chemoresistance was investigated at multiple levels. Chemoresistant ovarian cancers exhibited higher purine abundance and NEK6 expression. Inhibiting NEK6 led to decreased de novo purine synthesis, resulting in diminished chemoresistance in ovarian cancer cells. Mechanistically, NEK6 directly interacted with FOXO3, contributing to the phosphorylation of FOXO3 at S7 through its kinase activity, thereby inhibiting its nuclear translocation. Nuclear FOXO3 promoted FBXW7 transcription, leading to c-MYC ubiquitination and suppression of de novo purine synthesis. Paeonol, by inhibiting NEK6, suppressed de novo purine synthesis and enhanced chemosensitivity. The NEK6-mediated reprogramming of de novo purine synthesis emerges as a critical pathway influencing chemoresistance in ovarian cancer. Paeonol exhibits the potential to interfere with NEK6, thereby inhibiting chemoresistance.

Asunto(s)

Resistencia a Antineoplásicos , Proteína Forkhead Box O3 , Quinasas Relacionadas con NIMA , Neoplasias Ováricas , Proteínas Proto-Oncogénicas c-myc , Purinas , Femenino , Humanos , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Proteína Forkhead Box O3/metabolismo , Proteína Forkhead Box O3/genética , Resistencia a Antineoplásicos/efectos de los fármacos , Purinas/farmacología , Purinas/metabolismo , Línea Celular Tumoral , Animales , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Quinasas Relacionadas con NIMA/metabolismo , Quinasas Relacionadas con NIMA/genética , Ratones , Ratones Desnudos , Núcleo Celular/metabolismo , Proteína 7 que Contiene Repeticiones F-Box-WD/metabolismo , Proteína 7 que Contiene Repeticiones F-Box-WD/genética , Proliferación Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos

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Enhanced spontaneous bladder contractions (SBCs) have been thought one of the important underlying mechanisms for detrusor overactivity (DO). Piezo1 channel has been demonstrated involved in bladder function and dysfunction in rodents. We aimed to investigate the modulating role of Piezo1 in SBCs activity of human bladder. Human bladder tissues were obtained from 24 organ donors. SBCs of isolated bladder strips were recorded in organ bath. Piezo1 expression was examined with reverse transcription-quantitative polymerase chain reaction and immunofluorescence staining. ATP and acetylcholine release in cultured human urothelial cells was measured. Piezo1 is abundantly expressed in the bladder mucosa. Activation of Piezo1 with its specific agonist Yoda1 (100 nM-100 µM) enhanced the SBCs activity in isolated human bladder strips in a concentration-dependent manner. The effect of Yoda1 mimicked the effect of a low concentration (30 nM) of carbachol, which can be attenuated by removing the mucosa, blocking muscarinic receptors with atropine (1 µM), and blocking purinergic receptors with pyridoxal-phosphate-6-azophenyl-2',4'-disulfonate (PPADS, 30 µM), but not by tetrodotoxin (1 µM). Activation of urothelial Piezo1 with Yoda1 (30 µM) or hypotonic solution induced the release of ATP and acetylcholine in cultured human urothelial cells. In patients with benign prostatic hyperplasia, greater Piezo1 expression was observed in bladder mucosa from patients with DO than patients without DO. We conclude that upregulation and activation of Piezo1 may contribute to DO generation in patients with bladder outlet obstruction by promoting the urothelial release of ATP and acetylcholine. Inhibition of Piezo1 may be a novel therapeutic approach in the treatment of overactive bladder.

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Widespread adoption for substitutes of artificial bone grafts based on proper bioceramics has been generated in recent years. Among them, calcium-silicate-based bioceramics, which possess osteoconductive properties and can directly attach to biological organs, have attracted substantial attention for broad ranges of applications in bone tissue engineering. Approaches exist for a novel strategy to promote the drawbacks of bioceramics such as the incorporation of Zn2+, Mg2+, and Zr4+ ions into calcium-silicate networks, and the improvement of their physical, mechanical, and biological properties. Recently, hardystonite (Ca2ZnSi2O7) bioceramics, as one of the most proper calcium-silicate-based bioceramics, has presented excellent biocompatibility, bioactivity, and interaction. Due to its physical, mechanical, and biological behaviors and ability to be shaped utilizing a variety of fabrication techniques, hardystonite possesses the potential to be applied in biomedical and tissue engineering, mainly bone tissue engineering. A notable potential exists for the newly developed bioceramics to help therapies supply clinical outputs. The promising review paper has been presented by considering major aims to summarize and discuss the most applicable studies carried out for its physical, mechanical, and biological behaviors.

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As a byproduct of steelmaking, steel slag occupies significant land resources and poses potential environmental and safety challenges due to its extensive accumulation. Recently, steel slag has shown promising applications in the field of concrete. However, considering the complexity of the plateau environment, the utilization of steel slag is relatively lacking, and its low reactivity and poor volume stability remain the main factors restricting its application in plateau concrete. This paper reviews the research status of steel slag activation techniques for concrete, including wet grinding, chemi-excitation, high-temperature activation, and carbonation treatment. The effects of different treatment techniques on the mechanical and durability properties of concrete and the potential issues are discussed. Although different modification methods can improve the activity and volume stability of steel slag to varying degrees, a single modification technology is difficult to achieve the high-quality utilization of steel slag in concrete on the plateau. Based on this, a steel slag grading grinding-magnetic separation utilization technique suitable for high-altitude areas is proposed, which is beneficial for improving the added value and utilization rate of steel slag in concrete.

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BACKGROUND: Primary familial brain calcification (PFBC) is a monogenic disorder characterized by bilateral calcifications in the brain. The genetic basis remains unknown in over half of the PFBC patients, indicating the existence of additional novel causative genes. NAA60 was a recently reported novel causative gene for PFBC. OBJECTIVE: The aim was to identify the probable novel causative gene in an autosomal recessive inherited PFBC family. METHODS: We performed a comprehensive genetic study on a consanguineous Chinese family with 3 siblings diagnosed with PFBC. We evaluated the effect of the variant in a probable novel causative gene on the protein level using Western blot, immunofluorescence, and coimmunoprecipitation. Possible downstream pathogenic mechanisms were further explored in gene knockout (KO) cell lines and animal models. RESULTS: We identified a PFBC co-segregated homozygous variant of c.460_461del (p.D154Lfs*113) in NAA60. Functional assays showed that this variant disrupts NAA60 protein localization to Golgi and accelerated protein degradation. The mutant NAA60 protein alters its interaction with the PFBC-related proteins PiT2 and XPR1, affecting intracellular phosphate homeostasis. Further mass spectrometry analysis in NAA60 KO cell lines revealed decreased expression of multiple brain calcification-associated proteins, including reduced folate carrier (RFC), a folate metabolism-related protein. CONCLUSIONS: Our study replicated the identification of NAA60 as a novel causative gene for autosomal recessive PFBC, demonstrating our causative variant leads to NAA60 loss of function. The NAA60 loss of function disrupts not only PFBC-related proteins (eg, PiT2 and XPR1) but also a wide range of other brain calcification-associated membrane protein substrates (eg, RFC), and provided a novel probable pathogenic mechanism for PFBC. © 2024 International Parkinson and Movement Disorder Society.

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Luteolin-7-O-glucoside(L7G), a glycosylation product of luteolin, is present in a variety of foods, vegetables, and medicinal herbs and is commonly used in dietary supplements due to its health benefits. Meanwhile, luteolin-7-O-glucoside is an indicator component for the quality control of honeysuckle in the pharmacopoeia. However, its low content in plants has hindered its use in animal pharmacological studies and clinical practice. In this study, a novel 7-O-glycosyltransferase CmGT from Cucurbita moschata was cloned, which could efficiently convert luteolin into luteolin-7-O-glucoside under optimal conditions (40 °C and pH 8.5). To further improve the catalytic efficiency of CmGT, a 3D structure of CmGT was constructed, and directed evolution was performed. The mutant CmGT-S16A-T80W was obtained by using alanine scanning and iterative saturation mutagenesis. This mutant exhibited a kcat/Km value of 772 s-1·M-1, which was 3.16-fold of the wild-type enzyme CmGT. Finally, by introducing a soluble tag and UDPG synthesis pathway, the strain BXC was able to convert 1.25 g/L of luteolin into 1.91 g/L of luteolin-7-O-glucoside under optimal conditions, achieving a molar conversion rate of 96% and a space-time yield of 27.08 mg/L/h. This study provides an efficient method for the biosynthesis of luteolin-7-O-glucoside, which holds broad application prospects in the food and pharmaceutical industry.

Asunto(s)

Biocatálisis , Cucurbita , Glucósidos , Glicosiltransferasas , Luteolina , Proteínas de Plantas , Glucósidos/metabolismo , Glucósidos/química , Glucósidos/biosíntesis , Luteolina/química , Luteolina/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/química , Glicosiltransferasas/genética , Glicosiltransferasas/metabolismo , Glicosiltransferasas/química , Cucurbita/genética , Cucurbita/enzimología , Cucurbita/química , Cucurbita/metabolismo , Clonación Molecular , Cinética , Evolución Molecular Dirigida

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Loss of ovarian homeostasis is associated with ovary dysfunction and female diseases; however, the underlying mechanisms responsible for the establishment of homeostasis and its function in the ovary have not been fully elucidated. Here, we showed that conditional knockout of Rab37 in oocytes impaired macroautophagy/autophagy proficiency in the ovary and interfered with follicular homeostasis and ovary development in mice. Flunarizine treatment upregulated autophagy, thus rescuing the impairment of follicular homeostasis and ovarian dysfunction in rab37 knockout mice by reprogramming of homeostasis. Notably, both the E2F1 and EGR2 transcription factors synergistically activated Rab37 transcription and promoted autophagy. Thus, RAB37-mediated autophagy ensures ovary function by maintaining ovarian homeostasis.Abbreviations: AMH: anti-Mullerian hormone; ATG: autophagy related; BECN1: beclin 1; cKO: conditional knockout; Cre: cyclization recombination enzyme; dpp: days postpartum; E2: estradiol; E2F1: E2F transcription factor 1; EBF1: EBF transcription factor 1; EGR2: early growth response 2; FSH: follicle stimulating hormone; LH: luteinizing hormone; mpp: months postpartum; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; RAB37: RAB37, member RAS oncogene family; SQSTM1: sequestosome 1; TFEB: transcription factor EB; Zp3: zona pellucida glycoprotein 3.

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Objective. To address the quality and accuracy issues in the distribution of nanophosphors (NPs) using Cone-beam x-ray luminescence computed tomography (CB-XLCT) by proposing a novel reconstruction strategy.Approach. This paper introduces a sparse Bayesian learning reconstruction method termed SBL-LCGL, which is grounded in the Lipschitz continuous gradient condition and the Laplace prior to overcome the ill-posed inverse problem inherent in CB-XLCT.Main results. The SBL-LCGL method has demonstrated its effectiveness in capturing the sparse features of NPs and mitigating the computational complexity associated with matrix inversion. Both numerical simulation andin vivoexperiments confirm that the method yields satisfactory imaging results regarding the position and shape of the targets.Significance. The advancements presented in this work are expected to enhance the clinical applicability of CB-XLCT, contributing to its broader adoption in medical imaging and diagnostics.

Asunto(s)

Teorema de Bayes , Tomografía Computarizada de Haz Cónico , Procesamiento de Imagen Asistido por Computador , Tomografía Computarizada de Haz Cónico/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Luminiscencia , Aprendizaje Automático

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Background: Porcine deltacoronavirus (PDCoV) is a newly discovered porcine intestinal pathogenic coronavirus with a single-stranded positive-sense RNA genome and an envelope. PDCoV infects pigs of different ages and causes acute diarrhea and vomiting in newborn piglets. In severe cases, infection leads to dehydration, exhaustion, and death in sick piglets, entailing great economic losses on pig farms. The clinical symptoms of PDCoV infection are very similar to those of other porcine enteroviruses. Although it is difficult to distinguish these viral infections without testing, monitoring PDCoV is very important because it can spread in populations. The most commonly used methods for the detection of PDCoV is qPCR, which is time-consuming and require skilled personnel and equipment. Many farms cannot meet the conditions required for detection. Therefore, it is necessary to establish a faster and more convenient method for detecting PDCoV. Aims: To establish a rapid and convenient detection method for PDCoV by combining RPA (Recombinase Polymerase Isothermal Amplification) with CRISPR/Cas13a. Methods: Specific RPA primers and crRNA for PDCoV were designed, and the nucleic acids in the samples were amplified with RPA. Fluorescent CRISPR/Cas13a detection was performed. We evaluated the sensitivity and specificity of the RPA-CRISPR/Cas13a assay using qPCR as the control method. Results: CRISPR/Cas13a-assisted detection was completed within 90 min. The minimum detection limit of PDCoV was 5.7 × 101 copies/µL. A specificity analysis showed that the assay did not cross-react with three other porcine enteroviruses. Conclusion: The RPA-CRISPR/Cas13a method has the advantages of high sensitivity, strong specificity, fast response, and readily accessible results, and can be used for the detection of PDCoV.

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The management of produced water (PW) generated during oil and gas operations requires effective treatment and comprehensive chemical and toxicological assessment to reduce the environmental risks associated with reuse or discharge. This study evaluated a treatment train that included a low-temperature thermal distillation pilot system followed by granular activated carbon (GAC) and zeolite post-treatment for processing hypersaline Permian Basin PW. Our study provides a unique and comprehensive assessment of the treatment efficiency considering a targeted chemical scheme together with whole effluent toxicity (WET) tests across four trophic levels regarding aquatic critical receptors of concern (ROC): Raphidocelis subcapitata, Vibrio fischeri, Ceriodaphnia dubia, and Danio rerio. The distillate from the thermal distillation process met various numeric discharge standards for salinity and major ions. However, it did not meet toxicity requirements established by the United States National Pollutant Discharge Elimination System program. Subsequent post-treatment using GAC and zeolite reduced the concentration of potential stressors, including volatile organics, NH3, Cd, Cr, Zn, and Mn in the final effluent to below detection limits. This resulted in a consistent toxicity reduction across all WET tests, with no observable adverse effects for R. subcapitata, C. dubia, and D. rerio (no observed effect concentration >100%), and V. fischeri effects reduced to 19%. This study realizes the feasibility of treating PW to non-toxic levels and meeting reuse and discharge requirements. It underscores the importance of implementing integrated treatment trains to remove the contaminants of concern and provides a systematic decision framework to predict and monitor environmental risks associated with PW reuse.

Asunto(s)

Aliivibrio fischeri , Benchmarking , Carbón Orgánico , Daphnia , Destilación , Contaminantes Químicos del Agua , Pez Cebra , Zeolitas , Zeolitas/química , Animales , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/toxicidad , Aliivibrio fischeri/efectos de los fármacos , Carbón Orgánico/química , Daphnia/efectos de los fármacos , Purificación del Agua/métodos , Eliminación de Residuos Líquidos/métodos , Aguas Residuales/química

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BACKGROUND: Few large-scale studies have evaluated the effectiveness of percutaneous coronary intervention (PCI) technological advances in the treatment of patients with unprotected left main coronary artery disease (LM-CAD). We aim to identify independent factors that affect the prognosis of PCI in patients with unprotected LM-CAD and to assess the impact of PCI technological advances on long-term clinical outcomes. METHODS AND RESULTS: A total of 4512 consecutive patients who underwent unprotected LM-CAD PCI at Fuwai Hospital from 2004 to 2016 were enrolled. Multivariable Cox proportional hazards model was used to identify which techniques can independently affect the incidence of major adverse cardiac events (MACEs; a composite of cardiac death, myocardial infarction, or target vessel revascularization). The incidence of 3-year MACEs was 9.0% (406/4512). Four new PCI techniques were identified as the independent protective factors of MACEs, including second-generation drug-eluting stents (hazard ratio [HR], 0.61 [95% CI, 0.37-0.99]), postdilatation (HR, 0.75 [95% CI, 0.59-0.94]), final kissing balloon inflation (HR, 0.78 [95% CI, 0.62-0.99]), and using intravascular ultrasound (HR, 0.78 [95% CI, 0.63-0.97]). The relative hazard of 3-year MACEs was reduced by ≈50% with use of all 4 techniques compared with no technique use (HR, 0.53 [95% CI, 0.32-0.87]). CONCLUSIONS: PCI technological advances including postdilatation, second-generation drug-eluting stent, final kissing balloon inflation, and intravascular ultrasound guidance were associated with improved clinical outcomes in patients who underwent unprotected LM-CAD PCI.

Asunto(s)

Enfermedad de la Arteria Coronaria , Stents Liberadores de Fármacos , Intervención Coronaria Percutánea , Humanos , Femenino , Masculino , Enfermedad de la Arteria Coronaria/terapia , Enfermedad de la Arteria Coronaria/cirugía , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/tendencias , Intervención Coronaria Percutánea/instrumentación , Intervención Coronaria Percutánea/métodos , Anciano , Persona de Mediana Edad , Resultado del Tratamiento , Factores de Riesgo , Estudios Retrospectivos , Factores de Tiempo , China/epidemiología , Medición de Riesgo

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This study presents a comprehensive analysis of global, regional, and national trends in the burden of hearing loss (HL) among children and adolescents from 1990 to 2019, using data from the Global Burden of Disease study. Over this period, there was a general decline in HL prevalence and years lived with disability (YLDs) globally, with average annual percentage changes (AAPCs) of -0.03% (95% uncertainty interval [UI], -0.04% to -0.01%; p = 0.001) and -0.23% (95% UI, -0.25% to -0.20%; p < 0.001). Males exhibited higher rates of HL prevalence and YLDs than females. Mild and moderate HL were the most common categories across all age groups, but the highest proportion of YLDs was associated with profound HL [22.23% (95% UI, 8.63%-57.53%)]. Among females aged 15-19 years, the prevalence and YLD rates for moderate HL rose, with AAPCs of 0.14% (95% UI, 0.06%-0.22%; p = 0.001) and 0.13% (95% UI, 0.08%-0.18%; p < 0.001). This increase is primarily attributed to age-related and other HL (such as environmental, lifestyle factors, and occupational noise exposure) and otitis media, highlighting the need for targeted research and interventions for this demographic. Southeast Asia and Western Sub-Saharan Africa bore the heaviest HL burden, while High-income North America showed lower HL prevalence and YLD rates but a slight increasing trend in recent years, with AAPCs of 0.13% (95% UI, 0.1%-0.16%; p < 0.001) and 0.08% (95% UI, 0.04% to 0.12%; p < 0.001). Additionally, the analysis revealed a significant negative correlation between sociodemographic index (SDI) and both HL prevalence (r = -0.74; p < 0.001) and YLD (r = -0.76; p < 0.001) rates. However, the changes in HL trends were not significantly correlated with SDI, suggesting that factors beyond economic development, such as policies and cultural practices, also affect HL. Despite the overall optimistic trend, this study emphasizes the continued need to focus on specific high-risk groups and regions to further reduce the HL burden and enhance the quality of life for affected children and adolescents.

Asunto(s)

Carga Global de Enfermedades , Salud Global , Pérdida Auditiva , Humanos , Adolescente , Niño , Femenino , Prevalencia , Masculino , Pérdida Auditiva/epidemiología , Pérdida Auditiva/diagnóstico , Carga Global de Enfermedades/tendencias , Adulto Joven , Preescolar , Lactante , Distribución por Edad , Factores de Riesgo , Distribución por Sexo , Años de Vida Ajustados por Discapacidad/tendencias , Factores de Edad , Factores de Tiempo

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Achieving a desired whitening effect through short treatments without using peroxide and without compromising the integrity of tooth enamel remains a challenge in teeth whitening. Here, we developed a highly safe and efficient photodynamic therapy (PDT) strategy based on visible light-activated bismuth oxyiodide nanoparticles for nondestructive tooth whitening. The Bi7O9I3 nanoparticles (NPs) exhibited efficient photocatalytic activity owing to their narrow band gap, effectively harnessing the broad spectrum of visible light to generate ample electrons and holes. Meanwhile, the presence of oxygen vacancies, low oxidation state Bi3+ and the high specific surface area endow Bi7O9I3 NPs with effective electron-hole separation ability and potent redox potentials. Empowered by these characteristics, Bi7O9I3 NPs effectively catalyzed O2 into radicals (O2•-), facilitating the degradation of dental surface pigment molecules for tooth whitening. Concurrently, they eradicated oral bacteria and bacterial biofilms adhering to tooth surfaces, thereby having a positive effect on the effectiveness of tooth whitening. This PDT strategy with Bi7O9I3 NPs shows broad application prospects in tooth whitening.

Asunto(s)

Bismuto , Nanopartículas , Fotoquimioterapia , Blanqueamiento de Dientes , Bismuto/química , Bismuto/farmacología , Nanopartículas/química , Blanqueamiento de Dientes/métodos , Humanos , Biopelículas/efectos de los fármacos , Luz , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Tamaño de la Partícula , Yoduros/química , Yoduros/farmacología , Animales , Propiedades de Superficie

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The manipulation of interactions between light and matter plays a crucial role in the evolution of organisms and a better life for humans. As a result of natural selection, precise light-regulatory systems of biology have been engineered that provide many powerful and promising bioinspired strategies. As the "king of disguise", cephalopods, which can perfectly control the propagation of light and thus achieve excellent surrounding-matching via their delicate skin structure, have made themselves an exciting source of inspiration for developing optical and thermal regulation nanomaterials. This review presents cutting-edge advancements in cephalopod-inspired optical and thermal regulation nanomaterials, highlighting the key milestones and breakthroughs achieved thus far. We begin with the underlying mechanisms of the adaptive color-changing ability of cephalopods, as well as their special hierarchical skin structure. Then, different types of bioinspired nanomaterials and devices are comprehensively summarized. Furthermore, some advanced and emerging applications of these nanomaterials and devices, including camouflage, thermal management, pixelation, medical health, sensing and wireless communication, are addressed. Finally, some remaining but significant challenges and potential directions for future work are discussed. We anticipate that this comprehensive review will promote the further development of cephalopod-inspired nanomaterials for optical and thermal regulation and trigger ideas for bioinspired design of nanomaterials in multidisciplinary applications.

Asunto(s)

Cefalópodos , Nanoestructuras , Cefalópodos/química , Nanoestructuras/química , Animales , Temperatura , Humanos , Materiales Biomiméticos/química

RESUMEN

BACKGROUND: Lung cancer has maintained a high prevalence and mortality. Besides, venous thromboembolism (VTE) is the third most common disease of cardiovascular disease. Lung cancer with VTE usually influenced the overall survival in the follow-up. In the development of lung cancer, vigilance against and early diagnosis of VTE is of significance. METHODS: We searched the databases of PubMed, Web of Science, Embase and Cochrane for related research up to 30 November 2023 and extracted information of incidence, odds ratio (OR), hazard ratio (HR) and their 95% confidence intervals (CIs), for evaluating the incidence of VTE and its risk factors. RESULTS: A total of 54 articles and 873,292 records were included in our study. The pooled incidences of VTE and PE were 6% and 3%, respectively. Subgroup analysis revealed that the tumour, node and metastasis (TNM) stage (HR= 5.43, 95% CI: 2.42, 12.22), metastasis (HR= 2.67, 95% CI: 1.35, 5.29) and chemotherapy (HR= 2.27, 95% CI: 1.11, 4.65) had major influence on VTE occurrence. CONCLUSIONS: Lung cancer complicated with VTE is unignorable, and its occurrence varies widely by tumour staging, tissue type and treatment. The results may aid in clinical decision-making about lung cancer in higher risk with VTE and weather receiving anticoagulant prophylaxis.

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The pooled incidences of VTE and PE were 6% and 3% in lung cancer.LUAD, NSCLC and tumour stage III-IV have significant relevant with VTE in lung cancer.

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Neoplasias Pulmonares , Tromboembolia Venosa , Humanos , Incidencia , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/complicaciones , Estadificación de Neoplasias , Embolia Pulmonar/epidemiología , Embolia Pulmonar/etiología , Factores de Riesgo , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/etiología

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Polyploidization drives regulatory and phenotypic innovation. How the merger of different genomes contributes to polyploid development is a fundamental issue in evolutionary developmental biology and breeding research. Clarifying this issue is challenging because of genome complexity and the difficulty in tracking stochastic subgenome divergence during development. Recent single-cell sequencing techniques enabled probing subgenome divergent regulation in the context of cellular differentiation. However, analyzing single-cell data suffers from high error rates due to high-dimensionality, noise, and sparsity, and the errors stack up in polyploid analysis due to the increased dimensionality of comparisons between subgenomes of each cell, hindering deeper mechanistic understandings. Here, we developed a quantitative computational framework, pseudo-genome divergence quantification (pgDQ), for quantifying and tracking subgenome divergence directly at the cellular level. Further comparing with cellular differentiation trajectories derived from scRNA-seq data allowed for an examination of the relationship between subgenome divergence and the progression of development. pgDQ produces robust results and is insensitive to data dropout and noise, avoiding high error rates due to multiple comparisons of genes, cells, and subgenomes. A statistical diagonostic approach is proposed to identify genes that are central to subgenome divergence during development, which facilitates the integration of different data modalities, enabling the identification of factors and pathways that mediate subgenome-divergent activity during development. Case studies demonstrated that applying pgDQ to single cell and bulk tissue transcriptome data promotes a systematic and deeper understanding of how dynamic subgenome divergence contributes to developmental trajectories in polyploid evolution.

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Developing active sites with flexibility and diversity is crucial for single atom catalysts (SACs) towards sustainable nitrogen fixation at ambient conditions. Herein, the effects of doping main group metal elements (MGM) on the stability, catalytic activity, and selectivity of vanadium-based SACs is systematically investigated based on density functional theory calculations. It is found that the catalytic activity of V site can be significantly enhanced by the synergistic effect between MGM and vanadium atoms. More importantly, a volcano curve between the catalytic activity and the adsorption free energy of NNH* can be established, in which V-Pb dimer embedded on N-coordinated graphene (VPb-NG) exhibits optimal NRR activity due to its location at the top of volcano. Further analysis of electronic structures reveals that the unoccupancy ratio (eg/t2g) of V site is dramatically increased by the strong d-p orbital hybridization between V and Pb atoms, subsequently, N2 is activated to a larger extent. These interesting findings may provide a new path for designing active sites in SACs with excellent performance.

RESUMEN

Monosubstituted tetrazines are important bioorthogonal reactive tools due to their rapid ligation with trans-cyclooctene. However, their application is limited by the reactivity-stability paradox in biological environments. In this study, we demonstrated that steric effects are crucial in resolving this paradox through theoretical methods and developed a simple synthetic route to validate our computational findings, leading to the discovery of 1,3-azole-4-yl and 1,2-azole-3-yl monosubstituted tetrazines as superior bioorthogonal tools. These new tetrazines surpass previous tetrazines in terms of high reactivities and elevated stabilities. The most stable tetrazine exhibits a reasonable stability (71% remaining after 24 h incubation in cell culture medium) and an exceptionally high reactivity (k2 > 104 M-1 s-1 toward trans-cyclooctene). Due to its good stability in biological systems, a noncanonical amino acid containing such a tetrazine side chain was genetically encoded into proteins site-specifically via an expanded genetic code. The encoded protein can be efficiently labeled using cyclopropane-fused trans-cyclooctene dyes in living mammalian cells with an ultrafast reaction rate exceeding 107 M-1 s-1, making it one of the fastest protein labeling reactions reported to date. Additionally, we showed its superiority through in vivo reactions in living mice, achieving an efficient local anchoring of proteins. These tetrazines are expected to be optimal bioorthogonal reactive tools within living systems.

RESUMEN

DNA degradation has been a thorny problem in forensic science. Shortening the amplicon length of the genetic markers improves the analysis of degraded DNA effectively. Microhaplotype (MH) has been proposed as a potential genetic marker that can be used for degraded DNA analysis. In the present study, a 146-plex MH-next-generation sequencing (NGS) system with an average Ae of 6.876 was constructed. Unlike other MH studies, a single-primer extension (SPE)-based NGS library preparation method was used to improve the detection of MH markers for degraded DNA. SPE employs a locus-specific and universal primer to amplify target fragments, reducing the necessity for complete fragment sequences. SPE might effectively mitigate the impact of degradation on amplification. However, SPE produces amplicons of varying lengths, posing challenges in allele calling for SPE-NGS data. To address this issue, this study proposed a flexible allele-calling strategy to improve amplicon detection. In addition, this study evaluated the forensic efficacy of the system using 12 low-template samples (from 1 ng to 7.8 pg), 10 mock-degraded DNA with various degrees of degradation, and 8 forensic casework samples. When the template is as low as 7.8 pg, our system can accurately detect at least 37 loci and achieves a random match probability (RMP) of 10-30 using the complete allele-calling strategy. Eighty-two loci can be detected, and RMP can reach 10-54 using a flexible allele-calling strategy. After 150 min of 98°C treatment, 36 loci can still be detected, and an RMP of 10-5 can be obtained using the flexible allele-calling strategy. Furthermore, the number of single nucleotide polymorphism detected at different DNA amounts and degradation levels suggests that the SPE method combined with a flexible allele-calling strategy is effective.