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BACKGROUNDS: KLKs have been proved to be key regulators of the tumor microenvironment. In this study, we explored the potential of Kallikrein-related peptidases (KLKs) as clinical diagnostic and prognostic markers in patients with kidney renal clear cell carcinoma (KIRC) as well as their relationship with common immuno-inhibitor and immune cell infiltration in the tumor microenvironment to provide new targets and novel ideas for KIRC therapy. METHODS: Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), UCSC Xena, Genotype-Tissue Expression (GTEx), Kaplan-Meier plotter, cBioPortal, STRING, GeneMANIA, and TISIDB were used to analyze the differential expression, prognostic value, gene changes, molecular interaction, and immune infiltration of KLKs in patients with KIRC. RESULTS: From the gene expression level, it can be determined that KLK1, KLK6, and KLK7 are differentially expressed in KIRC and normal tissues. From the perspective of clinical prognosis, KLK1, KLK13, and KLK14 are highly correlated with the clinical prognosis of KIRC. The expression of KLKs is regulated by various immunosuppressive agents, with KDR, PVRL2, and VTCN1 being the most significant. The expression of KLKs is significantly correlated with the infiltration of various immune cells, of which Eosinophils and Neutrophils are the most significant. CONCLUSIONS: KLK1, KLK6, KLK7, KLK13, and KLK14 have potential as diagnostic and prognostic biomarkers, among which KLK1 is the most significant. This study may provide detailed immune information and promising targets for KIRC immunotherapy to assist in designing new immunotherapies.
Assuntos
Carcinoma de Células Renais , Biologia Computacional , Calicreínas , Neoplasias Renais , Humanos , Calicreínas/genética , Calicreínas/metabolismo , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Neoplasias Renais/genética , Neoplasias Renais/patologia , Neoplasias Renais/imunologia , Biologia Computacional/métodos , Regulação Neoplásica da Expressão Gênica , Prognóstico , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Perfilação da Expressão GênicaRESUMO
Patients with hemorrhagic stroke have high rates of morbidity and mortality, and drugs for prevention are very limited. Mendelian randomization (MR) analysis can increase the success rate of drug development by providing genetic evidence. Previous MR analyses only analyzed the role of individual drug target genes in hemorrhagic stroke; therefore, we used MR analysis to systematically explore the druggable genes for hemorrhagic stroke. We sequentially performed summary-data-based MR analysis and two-sample MR analysis to assess the associations of all genes within the database with intracranial aneurysm, intracerebral hemorrhage, and their subtypes. Validated genes were further analyzed by colocalization. Only genes that were positive in all three analyses and were druggable were considered desirable genes. We also explored the mediators of genes affecting hemorrhagic stroke incidence. Finally, the associations of druggable genes with other cardiovascular diseases were analyzed to assess potential side effects. We identified 56 genes that significantly affected hemorrhagic stroke incidence. Moreover, TNFSF12, SLC22A4, SPARC, KL, RELT, and ADORA3 were found to be druggable. The inhibition of TNFSF12, SLC22A4, and SPARC can reduce the risk of intracranial aneurysm, subarachnoid hemorrhage, and intracerebral hemorrhage. Gene-induced hypertension may be a potential mechanism by which these genes cause hemorrhagic stroke. We also found that blocking these genes may cause side effects, such as ischemic stroke and its subtypes. Our study revealed that six druggable genes were associated with hemorrhagic stroke, and the inhibition of TNFSF12, SLC22A4, and SPARC had preventive effects against hemorrhagic strokes.
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The utilization of seawater for hydrogen production via water splitting is increasingly recognized as a promising avenue for the future. The key dilemma for seawater electrolysis is the incompatibility of superior hydrogen- and oxygen-evolving activities at ampere-scale current densities for both cathodic and anodic catalysts, thus leading to large electric power consumption of overall seawater splitting. Here, in situ construction of Fe4N/Co3N/MoO2 heterostructure arrays anchoring on metallic nickel nitride surface with multilevel collaborative catalytic interfaces and abundant multifunctional metal sites is reported, which serves as a robust bifunctional catalyst for alkaline freshwater/seawater splitting at ampere-level current density. Operando Raman and X-ray photoelectron spectroscopic studies combined with density functional theory calculations corroborate that Mo and Co/Fe sites situated on the Fe4N/Co3N/MoO2 multilevel interfaces optimize the reaction pathway and coordination environment to enhance water adsorption/dissociation, hydrogen adsorption, and oxygen-containing intermediate adsorption, thus cooperatively expediting hydrogen/oxygen evolution reactions in base. Inspiringly, this electrocatalyst can substantially ameliorate overall freshwater/seawater splitting at 1000 mA cm-2 with low cell voltages of 1.65/1.69 V, along with superb long-term stability at 500-1500 mA cm-2 for over 200 h, outperforming nearly all the ever-reported non-noble electrocatalysts for freshwater/seawater electrolysis. This work offers a viable approach to design high-performance bifunctional catalysts for seawater splitting.
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The smart materials with multi-color and stimuli-responsive luminescence are very promising for next generation of optical information encryption and anti-counterfeiting, but these materials are still scarce. Herein, a multi-level information encryption strategy is developed based on the polychromatic emission of Sb-doped double perovskite powders (SDPPs). Cs2NaInCl6:Sb, Cs2KInCl6:Sb, and Cs2AgInCl6:Sb synthesized through coprecipitation methods exhibit broadband emissions with bright blue, cyan, and orange colors, respectively. The information transmitted by specific SDPP is encrypted when different SDPPs are mixed. The confidential information can be decrypted by selecting the corresponding narrowband filter. Then, an encrypted quick response (QR) code with improved security is demonstrated based on this multi-channel selection strategy. Moreover, the three types of SDPPs exhibit three different water-triggered luminescence switching behaviors. The confidential information represented by Cs2NaInCl6:Sb can be erased/recovered through a simple water spray/drying. Whereas, the information collected from the green channel is permanently erased by moisture, which fundamentally avoids information leakage. Therefore, different encryption schemes can be designed to meet a variety of encryption requirements. The multicolor and stimuli-responsive luminescence greatly enrich the flexibility of optical information encryption, which leaps the level of security and confidentiality.
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In the context of the vision to reach peak carbon dioxide emissions before 2030 and achieve carbon neutrality before 2060, Mainland China's agricultural development will face strict carbon constraints. This paper analyzes the agricultural land-use efficiency of Mainland China's agriculture under carbon emission constraint from 1996 to 2020, based on the unexpected super SBM (Slack-based measure)-Undesirable DEA, Malmquist index model, and quartile division-GIS method. The results show that: from 1996 to 2020, the agricultural output value per land and grain output per land show an upward trend, and the agricultural carbon emissions per land of most provinces show an increasing trend and larger emissions. The agricultural land-use efficiency in Mainland China rises first and then decreases, and technological progress is the decisive path to improving the agricultural land-use efficiency in Mainland China. The average MI in the prominent grain-selling area during 1996-2020 was as high as 1.071, which was significantly higher than that in the prominent grain-producing area (1.039) and the balance area (1.030). The improvement of agricultural land-use efficiency is mostly due to technological progress, but the instability of technical input and management in land use. To improve agricultural land-use efficiency in Mainland China, we should pay attention to the precise policy formulation of low-carbon and high-quality development and strengthen government investment in the difference between space resource endowment and development status.