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Solar steam interfacial evaporation represents a promising strategy for seawater desalination and wastewater purification owing to its environmentally friendly character1-3. To improve the solar-to-steam generation, most previous efforts have focused on effectively harvesting solar energy over the full solar spectrum4-7. However, the importance of tuning joint densities of states in enhancing solar absorption of photothermal materials is less emphasized. Here we propose a route to greatly elevate joint densities of states by introducing a flat-band electronic structure. Our study reveals that metallic λ-Ti3O5 powders show a high solar absorptivity of 96.4% due to Ti-Ti dimer-induced flat bands around the Fermi level. By incorporating them into three-dimensional porous hydrogel-based evaporators with a conical cavity, an unprecedentedly high evaporation rate of roughly 6.09 kilograms per square metre per hour is achieved for 3.5 weight percent saline water under 1 sun of irradiation without salt precipitation. Fundamentally, the Ti-Ti dimers and U-shaped groove structure exposed on the λ-Ti3O5 surface facilitate the dissociation of adsorbed water molecules and benefit the interfacial water evaporation in the form of small clusters. The present work highlights the crucial roles of Ti-Ti dimer-induced flat bands in enchaining solar absorption and peculiar U-shaped grooves in promoting water dissociation, offering insights into access to cost-effective solar-to-steam generation.
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Prostate cancer is the second most common cancer in men worldwide1. Over the past decade, large-scale integrative genomics efforts have enhanced our understanding of this disease by characterizing its genetic and epigenetic landscape in thousands of patients2,3. However, most tumours profiled in these studies were obtained from patients from Western populations. Here we produced and analysed whole-genome, whole-transcriptome and DNA methylation data for 208 pairs of tumour tissue samples and matched healthy control tissue from Chinese patients with primary prostate cancer. Systematic comparison with published data from 2,554 prostate tumours revealed that the genomic alteration signatures in Chinese patients were markedly distinct from those of Western cohorts: specifically, 41% of tumours contained mutations in FOXA1 and 18% each had deletions in ZNF292 and CHD1. Alterations of the genome and epigenome were correlated and were predictive of disease phenotype and progression. Coding and noncoding mutations, as well as epimutations, converged on pathways that are important for prostate cancer, providing insights into this devastating disease. These discoveries underscore the importance of including population context in constructing comprehensive genomic maps for disease.
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Povo Asiático/genética , Epigênese Genética , Epigenômica , Genoma Humano/genética , Genômica , Mutação , Neoplasias da Próstata/classificação , Neoplasias da Próstata/genética , Proteínas de Transporte/genética , Transformação Celular Neoplásica/genética , China , Estudos de Coortes , DNA Helicases/genética , Metilação de DNA , Proteínas de Ligação a DNA/genética , Regulação Neoplásica da Expressão Gênica , Fator 3-alfa Nuclear de Hepatócito/genética , Humanos , Masculino , Proteínas do Tecido Nervoso/genética , Neoplasias da Próstata/patologia , RNA-Seq , Transcriptoma/genéticaRESUMO
Carotenoids perform a broad range of important functions in humans; therefore, carotenoid biofortification of maize (Zea mays L.), one of the most highly produced cereal crops worldwide, would have a global impact on human health. PLASTID TERMINAL OXIDASE (PTOX) genes play an important role in carotenoid metabolism; however, the possible function of PTOX in carotenoid biosynthesis in maize has not yet been explored. In this study, we characterized the maize PTOX locus by forward- and reverse-genetic analyses. While most higher plant species possess a single copy of the PTOX gene, maize carries two tandemly duplicated copies. Characterization of mutants revealed that disruption of either copy resulted in a carotenoid-deficient phenotype. We identified mutations in the PTOX genes as being causal of the classic maize mutant, albescent1. Remarkably, overexpression of ZmPTOX1 significantly improved the content of carotenoids, especially ß-carotene (provitamin A), which was increased by ~threefold, in maize kernels. Overall, our study shows that maize PTOX locus plays an important role in carotenoid biosynthesis in maize kernels and suggests that fine-tuning the expression of this gene could improve the nutritional value of cereal grains.
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Oxirredutases , Zea mays , Humanos , Oxirredutases/genética , Oxirredutases/metabolismo , Zea mays/genética , Zea mays/metabolismo , Carotenoides/metabolismo , beta Caroteno/metabolismo , Grão Comestível/genética , Grão Comestível/metabolismo , Plastídeos/genética , Plastídeos/metabolismoRESUMO
MOTIVATION: Accurately detecting pathogenic microorganisms requires effective primers and probe designs. Literature-derived primers are a valuable resource as they have been tested and proven effective in previous research. However, manually mining primers from published texts is time-consuming and limited in species scop. RESULTS: To address these challenges, we have developed MiPRIME, a real-time Microbial Primer Mining platform for primer/probe sequences extraction of pathogenic microorganisms with three highlights: (i) comprehensive integration. Covering >40 million articles and 548 942 organisms, the platform enables high-frequency microbial gene discovery from a global perspective, facilitating user-defined primer design and advancing microbial research. (ii) Using a BioBERT-based text mining model with 98.02% accuracy, greatly reducing information processing time. (iii) Using a primer ranking score, PRscore, for intelligent recommendation of species-specific primers. Overall, MiPRIME is a practical tool for primer mining in the pan-microbial field, saving time and cost of trial-and-error experiments. AVAILABILITY AND IMPLEMENTATION: The web is available at {{https://www.ai-bt.com}}.
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Primers do DNA , Mineração de Dados , Mineração de Dados/métodos , Software , Bactérias/genética , Bactérias/classificaçãoRESUMO
Secreted phosphoprotein 1 (SPP1), also known as osteopontin, is a phosphorylated protein. High SPP1 expression levels have been detected in multiple cancers and are associated with poor prognosis and reduced survival rates. However, only a few pan-cancer analyses have targeted SPP1. We conducted a comprehensive analysis using multiple public databases, including TIMER and TCGA, to investigate the expression levels of SPP1 in 33 different tumor types. In addition, we verified the effect of SPP1 on osteosarcoma. To assess the impact of SPP1 on patient outcomes, we employed univariate Cox regression and Kaplan-Meier survival analyses to analyze overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in these tumor patients. We also explored SPP1 gene alterations in various tumor tissues using cBioPortal. We then examined the relationship between SPP1 and clinical characteristics, TME, immune regulatory genes, immune checkpoints, TMB, and MSI using R language. In addition, we used GSEA to investigate the molecular mechanisms underlying the role of SPP1. Bioinformatics analysis indicated that SPP1 was upregulated in 17 tumors. Overexpression of SPP1 results in poor OS, DSS, and PFI in CESC, ESCA, GBM, LGG, LIHC, PAAD, PRAD, and skin cutaneous melanoma. SPP1 expression was positively associated with immunocyte infiltration, immune regulatory genes, immune checkpoints, TMB, MSI, and drug sensitivity in certain cancers. We found that high expression of SPP1 in osteosarcoma was related to drug resistance and metastasis and further demonstrated that SPP1 can stimulate osteosarcoma cell proliferation via CCND1 by activating the PI3K/Akt pathway. These findings strongly suggest that SPP1 is a potential prognostic marker and novel target for cancer immunotherapy.
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Biomarcadores Tumorais , Osteopontina , Osteossarcoma , Humanos , Osteossarcoma/imunologia , Osteossarcoma/mortalidade , Osteossarcoma/genética , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Osteopontina/genética , Osteopontina/metabolismo , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Prognóstico , Neoplasias Ósseas/imunologia , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Regulação Neoplásica da Expressão Gênica , Linhagem Celular TumoralRESUMO
Rational construction of broadband and strong visible-light-absorbing (BSVLA) earth-abundant complexes is of great importance for efficient and sustainable solar energy utilization. Herein, we explore a universal Cu(I) center to couple with multiple strong visible-light-absorbing antennas to break the energy level limitations of the current noble-metal complexes, resulting in the BSVLA nonprecious complex (Cu-3). Systematic investigations demonstrate that double "ping-pong" energy-transfer processes in Cu-3 involving resonance energy transfer and Dexter mechanism enable a BSVLA between 430 and 620 nm and an antenna-localized long-lived triplet state for efficient intermolecular electron/energy transfer. Impressively, Cu-3 exhibited an outstanding performance for both energy- and electron-transfer reactions. Pseudo-first-order rate constant of photooxidation of 1,5-dihydroxynaphthalene with Cu-3 can achieve a record value of 190.8 × 10-3 min-1 among the molecular catalytic systems, over 30 times higher than that with a noble-metal photosensitizer (PS) [Ru(bpy)3]2+. These findings pave the way to develop BSVLA earth-abundant PSs for boosting photosynthesis.
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Complexos de Coordenação , Luz , Fotossíntese , Fármacos Fotossensibilizantes , Transferência de EnergiaRESUMO
BACKGROUND: CD74 is ectopically expressed in many tumors and can regulate tumor immunity. However, there are many gaps in the study of the prognostic value of CD74 expression and immune infiltration in hepatocellular carcinoma (HCC). METHODS: An online tumor database was searched to obtain data on gene/protein expression. Immune infiltration analysis was performed using the Tumor Immune Estimation Resource and Comprehensive Analysis on Multi-Omics of Immunotherapy in Pan-cancer databases. Single-cell data were obtained from the Tissue-specific Gene Expression and Regulation, Single-cell Transcriptomes of Tumor Immune Microenvironment and Tumor Immune Single-cell Hub 2 databases. RESULTS: CD74 was highly expressed in HCC patients. HCC patients with high CD74 expression who consumed alcohol or were negative for hepatitis virus had a better prognosis than patients with low CD74 expression. CD74 was mainly enriched in immune response regulation pathways. Both copy number variations in CD74 and CD74 expression patterns affected the infiltration levels of immune cells. Interestingly, CD74 regulated the differentiation of myeloid cells. CD74 in macrophages and dendritic cells (DCs) forms complex networks with malignant cells and hepatic progenitor cell (HPC)-like cells, respectively. High CD74 expression in HPC-like cells and malignant cells significantly decreased the fraction of C-type lectin domain family 9 A (CLEC9A)-cDC1+ DCs and IL-1B+ macrophages, respectively. Their crosstalk subsequently shaped the tumor microenvironment of HCC, possibly through the CD74-MIF axis. Importantly, patients with high CD74 expression presented higher immune scores and achieved good outcomes after receiving immunotherapy. CONCLUSION: High CD74 expression is associated with the abundance of a variety of immune cell types, mediating interactions among tumor and immune cells and shaping the malignant behavior of HCC. In summary, CD74 may be a hallmark for determining the prognosis and immune cell infiltration levels of HCC patients.
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Antígenos de Diferenciação de Linfócitos B , Carcinoma Hepatocelular , Antígenos de Histocompatibilidade Classe II , Imunoterapia , Neoplasias Hepáticas , Microambiente Tumoral , Humanos , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/etiologia , Microambiente Tumoral/imunologia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/etiologia , Antígenos de Diferenciação de Linfócitos B/metabolismo , Antígenos de Diferenciação de Linfócitos B/genética , Imunoterapia/métodos , Antígenos de Histocompatibilidade Classe II/metabolismo , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe II/imunologia , Prognóstico , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais , Biologia Computacional/métodosRESUMO
Synthesis of covalent organic framework nanosheets (CONs) with high aspect ratio is crucial to their assembly into advanced membranes. Nonetheless, the π-π stacking between covalent organic framework (COF) layers often leads to thick CONs. Herein, inspired by biomineralization process, a series of aspect ratio CONs >15 000 is synthesized by multifunctional polyelectrolytes which not only provide the nucleation sites for pre-assembly with COF monomer, but also suppress π-π interaction for anisotropic growth through protonation. The membrane assembled from CONs exhibited water permeance of 341 kg m-2 h-1 and salt rejection of 99.5% in desalination, outperforming ever-reported membranes. This method establishes a platform for the synthesis of crystalline nanosheets.
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ConspectusSolar-driven CO2 reduction into value-added chemicals, such as CO, HCOOH, CH4, and C2+ products, has been regarded as a potential way to alleviate environmental pollution and the energy crisis. In the past decades, numerous pioneered homogeneous catalytic systems composed of soluble photosensitizers (PSs) and catalytic active sites (CASs) have been explored for CO2 photoreduction. Nevertheless, inefficient electron migration based on random collision between CASs and PSs in homogeneous catalytic systems usually causes mediocre performance. Moreover, the relatively poor separation/recycling capability of the homogeneous systems has inevitably reduced their reusability and practicality. The rational combination of PSs and CASs have been proven to play critical roles in the development of highly efficient heterogeneous catalysts to improve their performance, such as anchoring them onto the solid matrixes or connecting them through bridging ligands. However, developing effective assembly strategies to achieve the ordered orientation and uniform heterogenization of PSs and CASs remains a great challenge, mainly due to the lack of crystallinity heterogeneous transformation and structural tailoring ability of traditional solid catalysts. Moreover, due to the lack of assembly and synthesis strategies, many efficient homogeneous photocatalytic systems are still unable to achieve high crystallinity heterogeneous transformation.Metal-organic frameworks (MOFs) and covalent-organic frameworks (COFs) have recently attracted broad interest toward CO2 photocatalysis because of their diverse precursors, well-defined and tailorable structures, abundant exposed CASs and high surface areas, etc. Especially, the highly ordered orientation and uniform combination of PSs and CASs in MOFs and COFs are beneficial for improved light harvesting and charge separation, greatly helping to address the aforementioned challenges. Moreover, the well-defined crystalline structures of MOFs and COFs facilitate the establishment of the structure-activity relationship. Therefore, it is increasingly important to summarize the integration of PSs and catalysts to provide deep insight into MOF/COF-based photocatalysts.In this Account, we summarize the ordered integration of PSs and CASs in MOFs and COFs for CO2 photoconversion and describe the structure-activity relationships to guide the design of effective catalysts. Given the unique structural features of MOFs and COFs, we have emphasized the integration of PSs and CASs to optimize their photocatalytic performance, including the confinement of catalytic active nanoparticles (NPs) into photosensitizing frameworks, co-coordination of PSs and CASs, and ligand-to-metal charge-transfer and anchoring CASs on the secondary building units of the photosensitizing frameworks. The catalytic activity, selectivity, sacrificial agent, and stability of these systems were then discussed. More importantly, MOFs and COFs provide powerful platforms to understand the key steps for boosting CO2 photoreduction and exploring the catalytic mechanism, involving light harvesting, electron-hole separation/migration, and surface redox reactions. Finally, the perspective and challenge of CO2 photoreduction in MOF/COF platforms are further proposed and discussed. It is expected that this Account would provide deep insight into the integration of PSs and catalysts in COFs and MOFs with well-defined structures and afford significant inspiration toward enhanced performance in heterogeneous catalysis.
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BACKGROUND: As the most malignant tumor of the female reproductive system, ovarian cancer (OC) has garnered increasing attention. The Warburg effect, driven by glycolysis, accounts for tumor cell proliferation under aerobic conditions. However, the metabolic heterogeneity linked to glycolysis in OC remains elusive. METHODS: We integrated single-cell data with OC to score glycolysis level in tumor cell subclusters. This led to the identification of a subcluster predominantly characterized by glycolysis, with a strong correlation to patient prognosis. Core transcription factors were pinpointed using hdWGCNA and metaVIPER. A specific transcription factor regulatory network was then constructed. A glycolysis-related prognostic model was developed and tested for estimating OC prognosis with a total of 85 machine-learning combinations, focusing on specific upregulated genes of two subtypes. We identified IGF2 as a key within the prognostic model and investigated its impact on OC progression and drug resistance through in vitro experiments, including the transwell assay, lactate production detection, and the CCK-8 assay. RESULTS: Analysis showed that the Malignant 7 subcluster was primarily related to glycolysis. Two OC molecular subtypes, CS1 and CS2, were identified with distinct clinical, biological, and microenvironmental traits. A prognostic model was built, and IGF2 emerged as a key gene linked to prognosis. Experiments have proven that IGF2 can promote the glycolysis pathway and the malignant biological progression of OC cells. CONCLUSIONS: We developed two novel OC subtypes based on glycolysis score, established a stable prognostic model, and identified IGF2 as the marker gene. These insights provided a new avenue for exploring OC's molecular mechanisms and personalized treatment approaches.
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Glicólise , Fator de Crescimento Insulin-Like II , Neoplasias Ovarianas , Análise de Célula Única , Humanos , Feminino , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/tratamento farmacológico , Glicólise/genética , Fator de Crescimento Insulin-Like II/genética , Fator de Crescimento Insulin-Like II/metabolismo , Prognóstico , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Proliferação de Células , Transcriptoma , Análise da Expressão Gênica de Célula ÚnicaRESUMO
BACKGROUND: Autophagy is a lysosome-dependent degradation pathway that regulates macrophage activation, differentiation, and polarization. Autophagy related 5 (Atg5) is a key protein involved in phagocytic membrane elongation in autophagic vesicles that forms a complex with Atg12 and Atg16L1. Alterations in Atg5 are related to both acute and chronic kidney diseases in experimental models. However, the role of macrophage-expressed Atg5 in acute kidney injury remains unclear. METHODS: Using a myeloid cell-specific Atg5 knockout (MΦ atg5-/-) mouse, we established renal ischemia/reperfusion and unilateral ureteral obstruction models to evaluate the role of macrophage Atg5 in renal macrophage migration and fibrosis. RESULTS: Based on changes in the serum urea nitrogen and creatinine levels, Atg5 deletion had a minimal effect on renal function in the early stages after mild injury; however, MΦ atg5-/- mice had reduced renal fibrosis and reduced macrophage recruitment after 4 weeks of ischemia/reperfusion injury and 2 weeks of unilateral ureteral obstruction injury. Atg5 deficiency impaired the CCL20-CCR6 axis after severe ischemic kidneys. Chemotactic responses of bone marrow-derived monocytes (BMDMs) from MΦ atg5-/- mice to CCL20 were significantly attenuated compared with those of wild-type BMDMs, and this might be caused by the inhibition of PI3K, AKT, and ERK1/2 activation. CONCLUSIONS: Our data indicate that Atg5 deficiency decreased macrophage migration by impairing the CCL20-CCR6 axis and inhibited M2 polarization, thereby improving kidney fibrosis.
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Obstrução Ureteral , Animais , Camundongos , Proteína 5 Relacionada à Autofagia/metabolismo , Fibrose , Isquemia/metabolismo , Rim/metabolismo , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Receptores CCR6/metabolismo , Obstrução Ureteral/complicações , Obstrução Ureteral/metabolismo , Obstrução Ureteral/patologiaRESUMO
Traditional Chinese medicine (TCM) has been extensively employed for the treatment of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there is demand for discovering more SARS-CoV-2 Mpro inhibitors with diverse scaffolds to optimize anti-SARS-CoV-2 lead compounds. In this study, comprehensive in silico and in vitro assays were utilized to determine the potential inhibitors from TCM compounds against SARS-CoV-2 Mpro, which is an important therapeutic target for SARS-CoV-2. The ensemble docking analysis of 18263 TCM compounds against 15 SARS-CoV-2 Mpro conformations identified 19 TCM compounds as promising candidates. Further in vitro testing validated three compounds as inhibitors of SARS-CoV-2 Mpro and showed IC50 values of 4.64 ± 0.11, 7.56 ± 0.78, and 11.16 ± 0.26 µM, with EC50 values of 12.25 ± 1.68, 15.58 ± 0.77, and 29.32 ± 1.25 µM, respectively. Molecular dynamics (MD) simulations indicated that the three complexes remained stable over the last 100 ns of production run. An analysis of the binding mode revealed that the active compounds occupy different subsites (S1, S2, S3, and S4) of the active site of SARS-CoV-2 Mpro via specific poses through noncovalent interactions with key amino acids (e.g., HIS 41, ASN 142, GLY 143, MET 165, GLU 166, or GLN 189). Overall, this study provides evidence indicating that the three natural products obtained from TCM could be further used for anti-COVID-19 research, justifying the investigation of Chinese herbal medicinal ingredients as bioactive constituents for therapeutic targets.
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COVID-19 , Proteases 3C de Coronavírus , Humanos , SARS-CoV-2/metabolismo , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Inibidores de Proteases/químicaRESUMO
BACKGROUND: Ischemia-reperfusion (I/R) injury is a major factor in liver damage following hepatic resection and liver transplantation, with anesthetics demonstrating the ability to shield organs from this type of injury. METHODS: Hypoxia-reoxygenation (H/R) was used to create in vitro I/R hepatocyte cell injury models. The CCK-8 assay, flow cytometer, LDH assay, and ELSIA were utilized to assess hepatocyte injury. The in vivo I/R injury rat model was then built. HE and TUNEL staining were used to assess liver tissue damage. Western-blot was applied to assess the activation of the MAPK/ERK pathway. RESULTS: Remimazolam (RMZL) remarkably improved cell viability and decreased apoptosis in H/R-induced hepatocyte injury. RMZL reduced the release of H/R-induced inflammatory mediators (TNF-α and IL-6) as well as LDH levels. We also discovered that RMZL inhibited p38 and ERK1/2 phosphorylation in vivo and in vitro. The stimulation of MAPK/ERK, on the other hand, abolished RMZL's anti-inflammation effects in H/R-induced hepatocyte injury. Furthermore, RMZL reduced liver tissue injury in I/R rats. CONCLUSION: RMZL prevented hepatic I/R damage by inhibiting MAPK/ERK signaling.
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Hepatócitos , Fígado , Sistema de Sinalização das MAP Quinases , Ratos Sprague-Dawley , Traumatismo por Reperfusão , Animais , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/metabolismo , Ratos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/fisiologia , Masculino , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/metabolismo , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Sobrevivência Celular/efeitos dos fármacos , BenzodiazepinasRESUMO
BACKGROUND: Individuals with osteoarthritis present with comorbidities, and the potential causal associations remain incompletely elucidated. The present study undertook a large-scale investigation about the causality between osteoarthritis and variable traits, using the summary-level data of genome-wide association studies (GWAS). METHODS: The present study included the summary-level GWS data of knee osteoarthritis, hip osteoarthritis, hip or knee osteoarthritis, hand osteoarthritis, and other 1355 traits. Genetic correlation analysis was conducted between osteoarthritis and other traits through cross-trait bivariate linkage disequilibrium score regression. Subsequently, latent causal variable analysis was performed to explore the causal association when there was a significant genetic correlation. Genetic correlation and latent causal variable analysis were conducted on the Complex Traits Genomics Virtual Lab platform ( https://vl.genoma.io/ ). RESULTS: We found 133 unique phenotypes showing causal relationships with osteoarthritis. Our results confirmed several well-established risk factors of osteoarthritis, such as obesity, weight, BMI, and meniscus derangement. Additionally, our findings suggested putative causal links between osteoarthritis and multiple factors. Socioeconomic determinants such as occupational exposure to dust and diesel exhaust, extended work hours exceeding 40 per week, and unemployment status were implicated. Furthermore, our analysis revealed causal associations with cardiovascular and metabolic disorders, including heart failure, deep venous thrombosis, type 2 diabetes mellitus, and elevated cholesterol levels. Soft tissue and musculoskeletal disorders, such as hallux valgus, internal derangement of the knee, and spondylitis, were also identified to be causally related to osteoarthritis. The study also identified the putative causal associations of osteoarthritis with digestive and respiratory diseases, such as Barrett's esophagus, esophagitis, and asthma, as well as psychiatric conditions including panic attacks and manic or hyperactive episodes. Additionally, we observed osteoarthritis causally related to pharmacological treatments, such as the use of antihypertensive medications, anti-asthmatic drugs, and antidepressants. CONCLUSION: Our study uncovered a wide range of traits causally associated with osteoarthritis. Further studies are needed to validate and illustrate the detailed mechanism of those causal associations.
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Diabetes Mellitus Tipo 2 , Osteoartrite do Quadril , Osteoartrite do Joelho , Humanos , Diabetes Mellitus Tipo 2/genética , Estudo de Associação Genômica Ampla , Herança Multifatorial , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Solid-state contact ion-selective electrodes (SC-ISEs) are an efficacious means of monitoring heavy metal contamination. Instability of the electrode potential is a key factor limiting their development, with biofouling in real water samples posing a significant challenge to maintaining stability. Therefore, addressing biofouling is crucial for optimizing solid-state ion-selective electrodes. In this work, high stability and antibiofouling capability in a solid-state contact lead ion-selective electrode (SC-Pb2+-ISE) based on polyaniline (PANI) was achieved through cathodic polarization. Specifically, PANI played a dual role in the ion-selective membrane (ISM) as an ion-to-electron transducer and antifouling agent. Given the excellent electrochemical performance of PANI, the prepared electrode (GC/PANI-Pb2+-ISM) demonstrated a remarkable antibiofouling efficiency of 98.2% under a cathodic polarization of -0.2 V. Furthermore, a standard deviation of standard potential (Eθ) as low as ± 0.5 mV was realized successfully. The excellent chrono-potentiometric stability of 17.0 ± 2.9 µV/s was also demonstrated. The electrode maintained a Nernstian response slope of 30.7 ± 0.2 (R2 = 0.998) after applying a cathode potential (-0.2 V) for 30 min. The developed GC/PANI-Pb2+-ISM electrode is suitable for practical applications in real environmental water sample monitoring.
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Multi-view stereo methods utilize image sequences from different views to generate a 3D point cloud model of the scene. However, existing approaches often overlook coarse-stage features, impacting the final reconstruction accuracy. Moreover, using a fixed range for all the pixels during inverse depth sampling can adversely affect depth estimation. To address these challenges, we present a novel learning-based multi-view stereo method incorporating attention mechanisms and an adaptive depth sampling strategy. Firstly, we propose a lightweight, coarse-feature-enhanced feature pyramid network in the feature extraction stage, augmented by a coarse-feature-enhanced module. This module integrates features with channel and spatial attention, enriching the contextual features that are crucial for the initial depth estimation. Secondly, we introduce a novel patch-uncertainty-based depth sampling strategy for depth refinement, dynamically configuring depth sampling ranges within the GRU-based optimization process. Furthermore, we incorporate an edge detection operator to extract edge features from the reference image's feature map. These edge features are additionally integrated into the iterative cost volume construction, enhancing the reconstruction accuracy. Lastly, our method is rigorously evaluated on the DTU and Tanks and Temples benchmark datasets, revealing its low GPU memory consumption and competitive reconstruction quality compared to other learning-based MVS methods.
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Natural reserves (NRs) play key roles in habitat integrity conservation and biodiversity loss mitigation, and the assessment of the conservation effectiveness of NRs is needed to better manage them. Habitat quality (HQ) comprehensively reflects habitat integrity and biodiversity, but the conservation effectiveness of NRs from the perspective of HQ has rarely been determined at high spatial resolution. Taking the southern section of the Hengduan Mountains (SSHM) in Southwest China as an example, combining an InVEST-HQ model and spatiotemporal change detection methods, the effectiveness of NRs from the perspective of HQ at 30-m spatial resolution was assessed in this study. The effectiveness disparities of NRs across different properties (i.e., management level, conservation target, size, and establishment age) was analyzed and the human pressures on NRs was investigated. The results showed that the HQ of the NRs is good in the SSHM, with the area ratio of the Higher and Highest HQ ≥ 93%. Most of the NR area (94.11%) was effective at improving or maintaining a good HQ. With regard to NR properties, county NRs, NRs designated to conserving wild animals, middle NRs, and younger NRs were more effective, corresponding to management level, conservation target, size, and establishment age, respectively. The human footprint for an effective area is significantly lower than that for an ineffective area, consistent with higher HQ in the effective area and lower HQ in the ineffective area. These findings support the management and zoning of NRs in the SSHM to ensure their effectiveness.
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Biodiversidade , Conservação dos Recursos Naturais , Ecossistema , China , Animais , HumanosRESUMO
BACKGROUND: The clinical efficacy and safety of intravenous immunoglobulin (IVIg) treatment for COVID-19 remain controversial. This study aimed to map the current status and gaps of available evidence, and conduct a meta-analysis to further investigate the benefit of IVIg in COVID-19 patients. METHODS: Electronic databases were searched for systematic reviews/meta-analyses (SR/MAs), primary studies with control groups, reporting on the use of IVIg in patients with COVID-19. A random-effects meta-analysis with subgroup analyses regarding study design and patient disease severity was performed. Our outcomes of interest determined by the evidence mapping, were mortality, length of hospitalization (days), length of intensive care unit (ICU) stay (days), number of patients requiring mechanical ventilation, and adverse events. RESULTS: We included 34 studies (12 SR/MAs, 8 prospective and 14 retrospective studies). A total of 5571 hospitalized patients were involved in 22 primary studies. Random-effects meta-analyses of very low to moderate evidence showed that there was little or no difference between IVIg and standard care or placebo in reducing mortality (relative risk [RR] 0.91; 95% CI 0.78-1.06; risk difference [RD] 3.3% fewer), length of hospital (mean difference [MD] 0.37; 95% CI - 2.56, 3.31) and ICU (MD 0.36; 95% CI - 0.81, 1.53) stays, mechanical ventilation use (RR 0.92; 95% CI 0.68-1.24; RD 2.8% fewer), and adverse events (RR 0.98; 95% CI 0.84-1.14; RD 0.5% fewer) of patients with COVID-19. Sensitivity analysis using a fixed-effects model indicated that IVIg may reduce mortality (RR 0.76; 95% CI 0.60-0.97), and increase length of hospital stay (MD 0.68; 95% CI 0.09-1.28). CONCLUSION: Very low to moderate certainty of evidence indicated IVIg may not improve the clinical outcomes of hospitalized patients with COVID-19. Given the discrepancy between the random- and fixed-effects model results, further large-scale and well-designed RCTs are warranted.
Assuntos
COVID-19 , Imunoglobulinas Intravenosas , Humanos , Imunoglobulinas Intravenosas/efeitos adversos , Estudos Prospectivos , Estudos Retrospectivos , Revisões Sistemáticas como AssuntoRESUMO
Floods are one of the most destructive disasters that cause loss of life and property worldwide every year. In this study, the aim was to find the best-performing model in flood sensitivity assessment and analyze key characteristic factors, the spatial pattern of flood sensitivity was evaluated using three machine learning (ML) models: Logistic Regression (LR), eXtreme Gradient Boosting (XGBoost), and Random Forest (RF). Suqian City in Jiangsu Province was selected as the study area, and a random sample dataset of historical flood points was constructed. Fifteen different meteorological, hydrological, and geographical spatial variables were considered in the flood sensitivity assessment, 12 variables were selected based on the multi-collinearity study. Among the results of comparing the selected ML models, the RF method had the highest AUC value, accuracy, and comprehensive evaluation effect, and is a reliable and effective flood risk assessment model. As the main output of this study, the flood sensitivity map is divided into five categories, ranging from very low to very high sensitivity. Using the RF model (i.e., the highest accuracy of the model), the high-risk area covers about 44% of the study area, mainly concentrated in the central, eastern, and southern parts of the old city area.
Assuntos
Inundações , Modelos Logísticos , Aprendizado de Máquina , China , Modelos Teóricos , Algoritmo Florestas AleatóriasRESUMO
Capturing short-lived intermediates at the molecular level is key to understanding the mechanism and dynamics of chemical reactions. Here, we have developed a paper-in-tip bipolar electrolytic electrospray mass spectrometry platform, in which a piece of triangular conductive paper incorporated into a plastic pipette tip serves not only as an electrospray emitter but also as a bipolar electrode (BPE), thus triggering both electrospray and electrolysis simultaneously upon application of a high voltage. The bipolar electrolysis induces a pair of redox reactions on both sides of BPE, enabling both electro-oxidation and electro-reduction processes regardless of the positive or negative ion mode, thus facilitating access to complementary structural information for mechanism elucidation. Our method enables real-time monitoring of transient intermediates (such as N,N-dimethylaniline radical cation, dopamine o-quinone (DAQ) and sulfenic acid with half-lives ranging from microseconds to minutes) and transient processes (such as DAQ cyclization with a rate constant of 0.15â s-1). This platform also provides key insights into electrocatalytic reactions such as Fe (III)-catalyzed dopamine oxidation to quinone species at physiological pH for neuromelanin formation.