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Materials with multifunctionality affect society enormously. However, the inability to surmount multiple functionality trade-offs limits the discovery of next-generation multifunctional materials. Departing from conventional alloying design philosophy, we present a hierarchical nanostructure (HNS) strategy to simultaneously break multiple performance trade-offs in a material. Using a praseodymium-cobalt (PrCo5) ferromagnet as a proof of concept, the resulting HNS outperforms contemporary high-temperature ferromagnets with a 50 to 138% increase in electrical resistivity while achieving their highest energy density. Our strategy also enables an exceptional thermal stability of coercivity (-0.148%/°C)-a key characteristic for device accuracy and reliability-surpassing that of existing commercial rare-earth magnets. The multifunctionality stems from the deliberately introduced nanohierarchical structure, which activates multiple micromechanisms to resist domain wall movement and electron transport, offering an advanced design concept for multifunctional materials.
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Cactus spinelike materials have attracted much attention due to high fog harvesting efficiency, but great challenges in structure fabrication and structural controllability still remain. In this study, we proposed a magnetically driven spray-coating method to fabricate a cactus spinelike superhydrophobic Fe3O4 vertical array on nonwoven cotton fabric. This method is simple and controllable; a mixture containing magnetic Fe3O4 particles and organosilicon resin was atomized into tiny droplets and arranged along the magnetic field lines. Different from the traditional method to prepare a cactus spinelike structure via liquid flow under magnet, which is usually accompanied with a big structure size and an unobvious structure feature due to the high viscosity of magnetic liquid. However, if the magnetic liquid is transformed into tiny magnetic droplets by a spraying method, it is promising to prepare micrometer-scale conical structures, and the reduction degree of bionic structures is high. When the fabricated structure is used for fog harvesting, it shows an extremely high efficiency of approximately 6.33 g cm-2 h-1, which is superior to most state-of-the-art fog harvesting materials. Considering the advantages of simplicity, structure controllability, and high fog harvesting rate, the reported strategy provides an avenue to build up high-performance fog harvesting materials.
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PRNP Q160X is one of the five dominantly inheritable nonsense mutations causing familial prion diseases. Till now, it remains unclear how this type of nonsense mutations causes familial prion diseases with unique clinical and pathological characteristics. Human prion protein (PrP) Q160X mutation is equivalent to Q159X in mouse PrP, which produces the mutant fragment PrP1-158. Through intracerebroventricular injection of recombinant adeno-associated virus in newborn mice, we successfully overexpressed mouse PrP1-158-FLAG in the central nervous system. Interestingly, high level PrP1-158-FLAG expression in the brain caused death in these mice with an average survival time of 60 ± 9.1 days. Toxicity correlated with levels of PrP1-158-FLAG but was independent of endogenous PrP. Histopathological analyses showed microgliosis and astrogliosis in mouse brains expressing PrP1-158-FLAG and most of PrP1-158-FLAG staining appeared intracellular. Biochemical characterization revealed that the majority of PrP1-158-FLAG were insoluble and a significant part of PrP1-158-FLAG appeared to contain an un-cleaved signal peptide that may contribute to its cytoplasmic localization. Importantly, an ~10-kDa proteinase K-resistant PrP fragment was detected, which was the same as those observed in patients suffering from this type of prion diseases. To our knowledge, this is the first animal study of familial prion disease caused by Q159X that recapitulates key features of human disease. It will be a valuable tool for investigating the pathogenic mechanisms underlying familial prion diseases caused by nonsense mutations.
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Purpose: Adverse childhood experiences (ACEs) have been associated with various aspects of morality, but their precise impact on moral decision-making remains unclear. This study aims to explore how ACEs influence moral decision-making in sacrificial dilemmas. Methods: Study 1 employed traditional dilemma analysis to quantify utilitarian responses and compare them among groups with no, low, and high ACEs. Study 2 utilized the CNI model to quantify three determinants of moral decision-making: sensitivity to consequences (C parameter), sensitivity to norms (N parameter), and general action tendencies (I parameter). Differences in these parameters among groups with no, low, and high ACEs were investigated. Results: Both Study 1 and Study 2 revealed that the high-ACE and low-ACE groups showed significantly higher utilitarian responses compared to the no-ACE group. However, no notable differences emerged between the high-ACE and low-ACE groups. Study 2 found that the N parameter was significantly lower in the high-ACE group compared to the low and no-ACE groups. Similarly, the low-ACE group exhibited significantly lower scores in the N parameter compared to the no-ACE group. Additionally, no significant differences were observed in the C and I parameters among groups with no, low, and high ACEs. Conclusion: These findings suggest that individuals with a high number of ACEs tend to exhibit more utilitarian responses, attributed to decreased affective response to the violation of moral rules, rather than increased deliberative cost-benefit reasoning or a general preference for action. Such insights deepen our understanding of the precise aspects of moral decision-making influenced by ACEs.
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The engineering of multifunctional structures with special surface wettability is highly desirable for all-weather freshwater production, but relevant research is scarce. In this study, a Janus conical vertical array was designed and fabricated via a magnetically driven spray-coating method for the first time. Benefiting from the special structure and wettability enhancement of the array in terms of solar absorption, fog capture and merging, droplet movement and evaporation area, all-weather freshwater production consisting of high-quality daytime solar vapor generation (water evaporation rate approximately 2.43 kg m-2 h-1, 1 kW m-2) and nighttime fog collection (water collection rate approximately 3.536 g cm-2 h-1) can be realized concurrently. When the designed array is employed for outdoor environments (114°35'E, 30°38'N, average daily temperature 34.9 °C, average daily humidity 64.0%), reliable and efficient daily pure water yields of 19.13 kg m-2-26.09 kg m-2 are obtainable. We believe that the proposed strategy for fabricating a Janus conical vertical array is novel in the integration of solar vapor generation and fog collection, which has great significance for all-weather freshwater production.
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This study addresses the challenge of designing simple and environmentally friendly methods for the preparation of effective electromagnetic wave (EMW) absorbing materials with tailored microstructures and multi-component regulation. N, O doped walnut-like porous carbon composite microspheres loaded with FeCo nanoparticles (WPCM/Fe-Co) are synthesized through high-temperature carbonization combined with soap-free emulsion polymerization and hydrothermal methods, avoiding the use of toxic solvents and complex conditions. The incorporation of magnetic components enhances magnetic loss, complementing dielectric loss to optimize EMW attenuation. The unique walnut-like morphology further improves impedance matching. The proportions of Fe and Co components can be adjusted to regulate the material's reflection loss, thickness, and bandwidth, allowing for fine-tuning of absorption performance. At a low filling ratio (16.7%), the optimal WPCM/Fe-Co composites exhibit a minimum reflection loss (RLmin) of -48.34 dB (10.33 GHz, 3.0 mm) and an overall effective absorbing bandwidth (EAB) covering the entire C bands, X bands, and Ku bands. This work introduces a novel approach to composition regulation and presents a green synthesis method for magnetic carbon composite absorbers with high-performance EMW absorption at low loading.
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BACKGROUND: In clinical medicine, low-dose radiographic image noise reduces the quality of the detected image features and may have a negative impact on disease diagnosis. OBJECTIVE: In this study, Adaptive Projection Network (APNet) is proposed to reduce noise from low-dose medical images. METHODS: APNet is developed based on an architecture of the U-shaped network to capture multi-scale data and achieve end-to-end image denoising. To adaptively calibrate important features during information transmission, a residual block of the dual attention method throughout the encoding and decoding phases is integrated. A non-local attention module to separate the noise and texture of the image details by using image adaptive projection during the feature fusion. RESULTS: To verify the effectiveness of APNet, experiments on lung CT images with synthetic noise are performed, and the results demonstrate that the proposed approach outperforms recent methods in both quantitative index and visual quality. In addition, the denoising experiment on the dental CT image is also carried out and it verifies that the network has a certain generalization. CONCLUSIONS: The proposed APNet is an effective method that can reduce image noise and preserve the required image details in low-dose radiographic images.
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Algoritmos , Tomografía Computarizada por Rayos X , Relación Señal-Ruido , Dosis de Radiación , Tomografía Computarizada por Rayos X/métodos , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
We verified whether social class shapes different models of the self in China, by integrating individuals' social mobility beliefs and exploring the mediating effect of sense of control. Participants were randomly assigned to one of 2 (subjective social class: upper vs. low class) × 2 (social mobility beliefs: high vs. low mobility) manipulation conditions. They then completed the sense of control questionnaire and self-focused attention task. High mobility belief could alleviate the difference in perception among different subjective social classes and improve lower classes' control perception. Sense of control mediates subjective social class effects and social mobility beliefs on self-focused attention.
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The analysis and communication of underwater images are often impeded by various elements such as blur, color cast, and noise. Existing restoration methods only address specific degradation factors and struggle with complex degraded images. Furthermore, traditional convolutional neural network (CNN) based approaches may only restore local color while ignoring global features. The proposed hybrid attention network combining CNN and Transformer focuses on addressing these issues. CNN captures local features and the Transformer uses multi-head self-attention to model global relationships. The network also incorporates degraded channel attention and supervised attention mechanisms to refine relevant features and correlations. The proposed method fared better than existing methods in a variety of qualitative criteria when evaluated against the public EUVP dataset of underwater images.
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BACKGROUND Optimizing surgical approaches for robot-assisted partial nephrectomy (RAPN) is vital for better patient outcomes. This retrospective study aimed to examine how visceral fat area (VFA) and body mass index (BMI) correlate with intraoperative complexities, thereby guiding the selection of surgical techniques for RAPN. MATERIAL AND METHODS The study analyzed the medical records of 213 Chinese patients diagnosed with a range of benign and malignant renal neoplasms and treated with RAPN in 2020. Visceral fat area was quantified using computed tomography (CT) scans taken at the umbilical level. Various perioperative indicators, such as demographic details, clinicopathological parameters, operation time, estimated blood loss (EBL), warm ischemic time (WIT), and intraoperative complications, were assessed. RESULTS For the retroperitoneal approach, patients with either visceral obesity or general obesity had longer operation times (P<0.001 and P=0.004) and had a tendency for higher EBL (P=0.003 and P=0.001) compared to non-obese patients. In the transperitoneal approach, those with visceral obesity had significantly longer operation times (P=0.008) than their non-viscerally obese counterparts; however, general obesity showed no impact on operation time (P=0.251). Estimated blood loss was higher for patients with visceral obesity (P=0.004), but no significant difference was noted among those with general obesity (P=0.980). CONCLUSIONS VFA appears to offer predictive advantages over BMI in assessing intraoperative complexities for transperitoneal RAPN. When used in conjunction with BMI, it could serve as a valuable tool in selecting the most appropriate surgical approach for RAPN.
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Neoplasias Renales , Procedimientos Quirúrgicos Robotizados , Robótica , Humanos , Índice de Masa Corporal , Obesidad Abdominal/complicaciones , Grasa Intraabdominal , Estudios Retrospectivos , Nefrectomía/métodos , Procedimientos Quirúrgicos Robotizados/métodos , Neoplasias Renales/cirugía , Neoplasias Renales/complicaciones , Obesidad/complicaciones , Resultado del TratamientoRESUMEN
High-quality solar evaporators with all-in-one design are highly desirable for vapor generation, but relevant research is scarce. In this study, a three-dimensional (3D) porous polypyrrole/polydopamine (PPY/PDA) structure was fabricated via a simple heating-assisted rapid oxidative polymerization method. The obtained evaporator has multiple features, and can simultaneously provide rapid water transport channels (average pore sizes â¼ 18.37 nm), low thermal conductivity (0.071 W m-1 K-1), high solar absorbance (97.08%), and good mechanical properties. When it is employed as an evaporator, the calculated water evaporation rate is approximately 2.12 kg m-2h-1, which is comparable to other reported 3D evaporators. Additionally, the evaporator displays great potential for purification toward various nonpotable water, as well as reliable pure water yields in an outdoor application (from 8:00 am to 5:00 pm, the evaporator can produce at least 13.95 L of drinkable water for a 1 m2 sample). We believe that the proposed strategy to fabricate all-in-one evaporators has great significance for scientific research and practical applications.
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Purpose: Although several studies have investigated the association between alexithymia and moral decision-making in sacrificial dilemmas, the evidence remains mixed. The current work investigated this association and how alexithymia affects moral choice in such dilemmas. Methods: The current research used a multinomial model (ie, CNI model) to disentangle (a) sensitivity to consequences, (b) sensitivity to moral norms, and (c) general preference for inaction versus action irrespective of consequences and norms in responses to moral dilemmas. Results: Higher levels of alexithymia were associated with a greater preference for utilitarian judgments in sacrificial dilemmas (Study 1). Furthermore, individuals with high alexithymia showed significantly weaker sensitivity to moral norms than did those with low alexithymia, whereas there were no significant differences in sensitivity to consequences or a general preference for inaction versus action (Study 2). Conclusion: The findings suggest that alexithymia affects moral choice in sacrificial dilemmas by blunting emotional reactions to causing harm, rather than through increased deliberative cost-benefit reasoning or general preference for inaction.
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SARS-CoV-2 mutation is minimized through a proofreading function encoded by NSP-14. Most estimates of the SARS-CoV-2 mutation rate are derived from population based sequence data. Our understanding of SARS-CoV-2 evolution might be enhanced through analysis of intra-host viral mutation rates in specific populations. Viral genome analysis was performed between paired samples and mutations quantified at allele frequencies (AF) ≥ 0.25, ≥ 0.5 and ≥ 0.75. Mutation rate was determined employing F81 and JC69 evolution models and compared between isolates with (ΔNSP-14) and without (wtNSP-14) non-synonymous mutations in NSP-14 and by patient comorbidity. Forty paired samples with median interval of 13 days [IQR 8.5-20] were analyzed. The estimated mutation rate by F81 modeling was 93.6 (95%CI 90.8-96.4], 40.7 (95%CI 38.9-42.6) and 34.7 (95%CI 33.0-36.4) substitutions/genome/year at AF ≥ 0.25, ≥ 0.5, ≥ 0.75 respectively. Mutation rate in ΔNSP-14 were significantly elevated at AF ≥ 0.25 vs wtNSP-14. Patients with immune comorbidities had higher mutation rate at all allele frequencies. Intra-host SARS-CoV-2 mutation rates are substantially higher than those reported through population analysis. Virus strains with altered NSP-14 have accelerated mutation rate at low AF. Immunosuppressed patients have elevated mutation rate at all AF. Understanding intra-host virus evolution will aid in current and future pandemic modeling.
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COVID-19 , Humanos , COVID-19/epidemiología , Tasa de Mutación , SARS-CoV-2/genética , Pandemias , Mutación , Genoma Viral/genéticaRESUMEN
OBJECTIVES: The vesicoprostatic muscle (VPM) is a longitudinal smooth muscle that originates from the trigone of the bladder or the opening of the ureter and is involved in urination as part of the detrusor apron. We explored the effect of VPM reconstruction on immediate and early recovery of urinary continence in patients undergoing robot-assisted laparoscopic radical prostatectomy (RALP). PATIENTS AND METHODS: A total of 523 patients with localized prostate cancer were enrolled from June 2018 to June 2020. All patients were diagnosed in our department based on magnetic resonance imaging and pathological findings on prostate biopsy. After 1:1 propensity score matching, 105 patient pairs were matched. The study was approved by our institutional review board and all surgeries were performed by three experienced high-volume surgeons. Demographic data, total operation time, pathological outcomes, the urinary continence rates of the two groups at different times after RALP, and factors influencing postoperative urinary continence after RALP were recorded. Student's t test was used to compare continuous variables and the Pearson χ2 test to compare categorical variables. Logistic regression analysis was used to identify factors affecting immediate and early postoperative urinary control. RESULTS: VPM reconstruction promoted immediate and early recovery of urinary continence (immediate continence, 66.67 vs. 40.00%, P = 0.000; 3-month continence, 80.95 vs. 64.76%, P = 0.008). CONCLUSIONS: VPM reconstruction improved immediate and early urinary continence in patients who underwent RALP.
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Laparoscopía , Neoplasias de la Próstata , Procedimientos Quirúrgicos Robotizados , Masculino , Humanos , Procedimientos Quirúrgicos Robotizados/métodos , Micción , Próstata/patología , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/patología , Prostatectomía/métodos , Músculos , Recuperación de la Función , Laparoscopía/métodosRESUMEN
Background: Germline pathogenic variants are estimated to affect 3-5% of patients with renal cell carcinoma (RCC). The identification of patients with hereditary RCC is important for cancer screening and treatment guidance. Methods: Whole-exome sequencing (WES) (n=69) or gene panel sequencing containing 139 genes (n=54) related to germline cancer predisposition was used to analyze germline mutations in 123 patients with RCC admitted to Department of Urology, The Third Medical Center of Chinese PLA General Hospital. Chi-square test (χ2) was used to analyze relationship between clinicopathologic parameters and germline mutations. Results: A total of 13 (10.57%) patients carried pathogenic or likely pathogenic germline mutations in 10 cancer predisposition genes, including VHL, FH, FLCN, SDHB, MUTYH, RAD51C, NBN, RAD50, FANCI, and FANCM. A total of 6 of these 10 cancer predisposition genes were associated with maintenance of genomic stability and DNA repair. Patients harboring pathogenic germline mutations tended to have an earlier RCC onset. The prevalence of deleterious mutations was higher in patients with bilateral or multifocal RCC compared to patients without bilateral or multifocal RCC. Patients with non-clear cell RCC (nccRCC) were significantly more likely to have RCC-associated gene mutations. Conclusions: To our knowledge, this is the first report of pathogenic germline mutations in the FANCI and FANCM genes and heterozygous germline missense mutation in exon 5 of the FH gene c.563A>T:p.N188I in RCC. Young RCC patients, patients with bilateral or multifocal RCC, or patients with nccRCC are more likely to have pathogenic/potentially pathogenic germline mutations.
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Many functional materials are approaching their performance limits due to inherent trade-offs between essential physical properties. Such trade-offs can be overcome by engineering a material that has an ordered arrangement of structural units, including constituent components/phases, grains, and domains. By rationally manipulating the ordering with abundant structural units at multiple length scales, the structural ordering opens up unprecedented opportunities to create transformative functional materials, as amplified properties or disruptive functionalities can be realized. In this perspective article, a brief overview of recent advances in the emerging ordered functional materials across catalytic, thermoelectric, and magnetic materials regarding the fabrication, structure, and property is presented. Then the possibility of applying this structural ordering strategy to highly efficient neuromorphic computing devices and durable battery materials is discussed. Finally, remaining scientific challenges are highlighted, and the prospects for ordered functional materials are made. This perspective aims to draw the attention of the scientific community to the emerging ordered functional materials and trigger intense studies on this topic.
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The subgenus Rhizirideum in the genus Allium consists of 38 species worldwide and forms five sections (A. sect. Rhizomatosa, A. sect. Tenuissima, A. sect. Rhizirideum, A. sect. Eduardia, and A. sect. Caespitosoprason), A. sect. Caespitosoprason being merged into A. sect. Rhizomatosa recently. Previous studies on this subgenus mainly focused on separate sections. To investigate the inter-section and inter-subgenera phylogenetic relationships and adaptive evolution of A. subg. Rhizirideum, we selected thirteen representative species, which cover five sections of this subgenus and can represent four typical phenotypes of it. We conducted the comparative plastome analysis with our thirteen plastomes. And phylogenetic inferences with CDSs and complete sequences of plastomes of our thirteen species and another fifty-four related species were also performed. As a result, the A. subg. Rhizirideum plastomes were relatively conservative in structure, IR/SC borders, codon usage, and repeat sequence. In phylogenetic results, the inter-subgenera relationships among A. subg. Rhizirideum and other genus Allium subgenera were generally similar to the previous reports. In contrast, the inter-section relationships within our subgenus A. subg. Rhizirideum were newly resolved in this study. A. sect. Rhizomatosa and A. sect. Tenuissima were sister branches, which were then clustered with A. sect. Rhizirideum and A. sect. Eduardia successively. However, Allium Polyrhizum Turcz. ex Regel, type species of A. sect. Caespitosoprason, was resolved as the basal taxon of A. subg. Rhizirideum. Allium siphonanthum J. M. Xu was also found in clade A. subg. Cyathophora instead of clade A. subg. Rhizirideum. The selective pressure analysis was also conducted, and most protein-coding genes were under purifying selection. At the same time, just one gene, ycf2, was found under positive selection, and another three genes (rbcL, ycf1a, ycf1b) presented relaxed selection, which were all involved in the photosynthesis. The low temperature, dry climate, and high altitude of the extreme habitats where A. subg. Rhizirideum species grow might impose intense natural selection forces on their plastome genes for photosynthesis. In summary, our research provides new insights into the phylogeny and adaptive evolution of A. subg. Rhizirideum. Moreover, we suggest that the positions of the A. subg. Rhizirideum species A. polyrhizum and A. siphonanthum should be reconsidered.
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Allium , Amaryllidaceae , Genoma de Plastidios , Allium/genética , Amaryllidaceae/genética , Filogenia , Secuencias Repetitivas de Ácidos Nucleicos , Evolución MolecularRESUMEN
Scarcity goods have generally been perceived as high in value in real-world and empirical studies. However, few studies have investigated this value over time, such as performance in intertemporal decision making. This study's chief objective was to determine how scarcity evaluation changes temporally. We used the electroencephalogram technique and an outcome evaluation task with the valuation of scarcity and ordinary rewards delivered at different times to explore the effect of scarcity on delay discounting. The feedback-related negativity (FRN) results show that ordinary goods were associated with a more negative amplitude than scarcity goods, and that rewards delivered in the future evoked more negative deflection compared to those delivered immediately. The prominent FRN effect was derived mainly from ordinary trials rather than scarcity trials in the immediate condition and in the future rather than only in the immediate condition. The Frontal Asymmetry Index (FAI) results show that the scarcity condition was associated with greater relative left frontal cortical activity than the ordinary condition when delivered immediately. The frontal asymmetry indicated greater approach motivation. Our electrophysiology data indicate that scarcity goods have a perceived high value, particularly when delivered immediately.
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Solar driven interfacial vapor generation is considered to be an effective strategy to alleviate the impact of water crisis on human activities. However, great efforts of researchers have been devoted to improving the solar steam generation efficiency, while less attention has been paid to the long-term stability of evaporators. Herein, we proposed a robust core-shell structured evaporator prepared by a simple fast curing assisted spray-coating method. Owing to the inherent superelasticity of melamine-formaldehyde (MF) sponge, the finely designed novel 3D core-shell structure, and the quick curing of branched polyethyleneimine (BPEI) and 5-pentaerythritol pentaacrylate (5Acl) induced special knot shaped photothermal coating, the as-obtained evaporator (CB/MF) performed well in vapor generation with a high water evaporation rate of 2.082 kg m-2 h-1 under 1 sun illumination, and the evaporation efficiency reached 123.5%, which is comparable to the state-of-the-art artificial solar evaporator. Even in strict application situations, such as long-term recycling testing for 40 h, 500 compression-release cycles (20%, 40% or 60%), sonication for 12 h, or shaking for 30 h, the water evaporation rate of the obtained evaporator remains at a high level of above 2.00 kg m-2 h-1. Additionally, the evaporator shows effective purification toward high-concentration brine, acid-base solutions, simulated seawater, dye wastewater, and heavy metal wastewater, as well as reliable pure water, providing an outdoor application. With the advantages of a high evaporation rate, stable long-term vapor generation, and effective purification toward various non-potable water sources, we believe that the fabricated core-shell structured CB/MF evaporator is a promising candidate for practical solar steam generation.
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Ferredoxin 1 (FDX1), an iron-sulphur protein, is responsible for electron transfer in a range of metabolic redox reactions. Clear cell renal cell carcinoma (ccRCC) is an aggressive cancer characterised by metabolic reprogramming, and FDX1 is a critical regulator of cuproptosis. However, the expression profile and prognostic value of FDX1 associated with clinicopathological features in ccRCC remain largely unelucidated. In this study, we integrated a series of public bioinformatic analysis to explore the mRNA and protein profiles of FDX1 across human cancers and cell lines and validated its expression and prognostic value, especially in ccRCC. In this study, FDX1 mRNA and protein expression were aberrantly downregulated and associated with ccRCC grade, stage, and nodal metastasis, whereas in adjacent non-tumour kidney tissue, it was abundantly expressed and cytoplasmically localised in renal tubular epithelial cells. Multivariate analysis indicated that low FDX1 expression contributed to unfavourable overall and disease-free survival. The functional enrichment of FDX1 co-expressed genes in ccRCC involved mainly mitochondrial dysfunction in various metabolic processes and biological oxidation, besides iron-sulphur cluster biogenesis. Furthermore, FDX1 modulates immunological infiltration to affect prognosis. Thus, FDX1 downregulation is mechanistically because of ccRCC tumourigenesis and is a promising prognostic biomarker to stratify patients with ccRCC.