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Dissolved black carbon (DBC) plays a crucial role in the migration and bioavailability of iron in water. However, the properties of DBC releasing under diverse pyrolysis conditions and dissolving processes have not been systematically studied. Here, the compositions of DBC released from biochar through redox processes dominated by bacteria and light were thoroughly studied. It was found that the DBC released from straw biochar possess more oxygen-containing functional groups and aromatic substances. The content of phenolic and carboxylic groups in DBC was increased under influence of microorganisms and light, respectively. The concentration of phenolic hydroxyl groups increased from 10.0â¼57.5 mmol/gC to 6.6 â¼65.2 mmol/gC, and the concentration of carboxyl groups increased from 49.7â¼97.5 mmol/gC to 62.1 â¼113.3 mmol/gC. Then the impacts of DBC on pyrite dissolution and microalgae growth were also investigated. The complexing Fe3+ was proved to play a predominant role in the dissolution of ferrous mineral in DBC solution. Due to complexing between iron ion and DBC, the amount of dissolved Fe in aquatic water may rise as a result of elevated number of aromatic components with oxygen containing groups and low molecular weight generated under light conditions. Fe-DBC complexations in solution significantly promoted microalga growth, which might be attributed to the stimulating effect of dissolved Fe on the chlorophyll synthesis. The results of study will deepen our understanding of the behavior and ultimate destiny of DBC released into an iron-rich environment under redox conditions.
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Carbono , Carbón Orgánico , Hierro , Oxidación-Reducción , Hierro/química , Carbón Orgánico/química , Carbono/química , Contaminantes Químicos del Agua/químicaRESUMEN
A novel ZnO/CuI/Cu foam electrode was constructed, which demonstrated excellent photoelectrocatalytic activity for the self-Fenton degradation of tetracycline in water. The H2O2 yield was 405.0 µmol L-1 over ZnO/CuI/Cu foam (CIZ-3) under light irradiation (100 mW cm-2) for 5 h at -1.23 V (vs NHE), which was 1.7 times higher than that of ZnO/Cu foam and 1.6 times higher than that of CuI/Cu foam, respectively. The 99.0% of tetracycline was degraded by CIZ-3 due to its efficient yield of H2O2 to self-catalyzed generation of â¢OH. The results of the open-circuit potential between CuI and ZnO displayed that the electrons from the conduction band of CuI flowed to ZnO and the holes from the valence band of ZnO migrated to CuI. As a result, the photogenerated electron-hole pairs of ZnO/CuI were efficiently separated, which greatly promoted the photoelectrocatalytic activity of ZnO/CuI/foam. The toxicity of the aqueous tetracycline solution was significantly reduced by observing the growth of Escherichia coli in the treated wastewater.
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Lodging presents a significant challenge in cultivating high-yield crops with extensive above-ground biomass, yet the molecular mechanisms underlying this phenomenon in the Solanaceae family remain largely unexplored. In this study, we identified a gene, CaSLR1 (Capsicum annuum Stem Lodging Resistance 1), which encodes a MYELOBLASTOSIS (MYB) family transcription factor, from a lodging-affected C. annuum EMS mutant. The suppression of CaSLR1 expression in pepper led to notable stem lodging, reduced thickness of the secondary cell wall, and decreased stem strength. A similar phenotype was observed in tomato with the knockdown of SlMYB61, the orthologous gene to CaSLR1. Further investigations demonstrated that CaNAC6, a gene involved in secondary cell wall (SCW) formation, is co-expressed with CaSLR1 and acts as a positive regulator of its expression, as confirmed through yeast one-hybrid, dual-luciferase reporter assays, and electrophoretic mobility shift assays. These findings elucidate the CaNAC6-CaSLR1 module that contributes to lodging resistance, emphasizing the critical role of CaSLR1 in the lodging resistance regulatory network.
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The severely low influent chemical oxygen demand (COD) concentration at wastewater treatment plants (WWTPs) has become a critical issue. A key factor is the excessive biodegradation of organic matter by microbial communities within sewer systems. Intense disinfection commonly adopted for medical wastewater leads to abundant residual chlorine entering sewers, likely causing significant changes in microbial communities and sewage quality in sewers, yet our understanding is limited. Through long-term sewer simulation batch tests, this study revealed the response mechanism of microbial communities to residual chlorine and its impact on organic matter concentration in sewage. Under residual chlorine stress, microbial community structure rapidly changed, and more complex microbial interactions were observed. Besides, pathways related to stress response such as two-component system were significantly enriched; pathways related to energy metabolism (such as carbon fixation in prokaryotes and citrate cycle) in microbial communities were inhibited, and carbon metabolism shifted from the Embden-Meyerhof pathway to the pentose phosphate pathway to enhance cellular reducing power, reduce oxidative stress, and consequently decrease organic matter degradation. Therefore, compared to sewers with normal disinfection, concentrations of COD and dissolved organic carbon in sewage under chlorine stress increased by 12.6 % and 7.4 %, respectively. Besides, the decay and transformation of residual chlorine in sewers were explored. These findings suggest a new approach to medical wastewater discharge management: placing the medical wastewater outlet at the upstream in sewer systems, which ensures that residual chlorine consumption reaches maximum during long-distance transportation, mitigating its harmful effects on WWTPs, and increases the influent organic matter concentration, thereby reducing the need for additional carbon sources.
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In this study, a one-step extrusion method is proposed to prepare blended polylactic acid (PLA)/thermoplastic starch (TPS) using a novel plant-derived compatibilizer, pyrogallic acid (PGA), to enhance the PLA/TPS compatibility. The effects of PGA on the mechanical behavior, fractured cross-section morphology, thermal and dynamic mechanical performance, and water resistance of PLA/TPS blends were systematically studied. Results demonstrate that the addition of PGA effectively improves the compatibility between TPS and PLA, resulting in enhanced tensile strength, crystallinity, elongation at break, thermal stability, and hydrophobicity of the blends. Specifically, incorporating 1.5 phr of PGA into the blend system yields the highest values for tensile strength (23.38 MPa) and elongation at break (16.96 %), which are 24.7 % and 233.2 %, respectively, higher than those observed for pure PLA/TPS blends. Furthermore, other properties exhibit obvious improvements upon incorporation of PGA into the blends. This approach provides a promising strategy for enhancing the performance of PLA/TPS blends and expanding their applications in food packaging, agricultural film, etc.
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Two Gram-stain-negative, aerobic, milk-white coloured, non-motile, short rod-shaped bacteria, designated as strains SYSU D60010T and SYSU D60012T, were isolated from sand samples collected from the Taklimakan Desert of Xinjiang Province in China. Both strains were positive for oxidase, catalase and nitrate reduction, but negative for amylase, H2S production, hydrolysis of gelatin and cellulase. Strains SYSU D60010T and SYSU D60012T grew well at 28â°C, at pH 7 and had the same NaCl tolerance range of 0-1â% (w/v). The major fatty acids (>5â%) of strains SYSU D60010T and SYSU D60012T were summed feature 8 (C18â:â1 ω7c and/or C18â:â1 ω6c), iso-C19â:â0 cyclo ω8c, C16â:â0 and iso-C18â:â1 2-OH. Q-10 was the only respiratory ubiquinone. Strains SYSU D60010T and SYSU D60012T showed high 16S rRNA gene sequence similarities to Aestuariivirga litoralis SYSU M10001T (94.2 and 94.1â%), Rhodoligotrophos jinshengii BUT-3T (92.0 and 91.9â%) and Rhodoligotrophos appendicifer 120-1T (91.8 and 91.7â%), and the genomes were 7.4 and 5.8 Mbp in size with DNA G+C contents of 62.8 and 63.0âmol%, respectively. Phylogenetic, phenotypic and chemotaxonomic characteristics indicated that these two strains represent a novel genus and two novel species within the family Aestuariivirgaceae. We propose the name Taklimakanibacter deserti gen. nov., sp. nov. for strain SYSU D60010T, representing the type strain of this species (=KCTC 52783T =NBRC 113344T) and Taklimakanibacter lacteus gen. nov., sp. nov. for strain SYSU D60012T, representing the type strain of this species (=KCTC 52785T=NBRC 113128T).
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Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano , Clima Desértico , Ácidos Grasos , Filogenia , ARN Ribosómico 16S , Análisis de Secuencia de ADN , Microbiología del Suelo , ARN Ribosómico 16S/genética , Ácidos Grasos/química , ADN Bacteriano/genética , China , Ubiquinona/análogos & derivados , Arena/microbiologíaRESUMEN
A novel rod-shaped bacterium, designated as strain SYSU D60015T that formed yellowish colonies was isolated from a sandy soil collected from the Kumtag Desert in Xinjiang, China. Cells were Gram-stain-negative, oxidase-positive, catalase-negative and motile with a single polar flagellum. Growth optimum occurred between 28 and 37 °C, pH 7.0 and with 0-0.5% (W/V) NaCl. The predominant cellular fatty acids (> 5%) were summed feature 8 (C18:1 ω7c and/or C18:1 ω6c), C19:0 cyclo ω8c, C18:1 ω7c 11-methyl and C16:0. The polar lipid profile contained one phosphatidylethanolamine, one diphosphatidylglycerol, one phosphatidylglycerol, one unidentified phospholipid, three unidentified aminolipids, two unidentified aminophospholipids and seven unidentified lipids. The only respiratory quinone was ubiquinone-10. Based on 16S rRNA gene sequence phylogenetic analysis, strain SYSU D60015T was found to form a distinct linage within the family Sneathiellaceae, and had 16S rRNA gene sequence similarities of 90.8% to Taonella mepensis H1T, and 90.2% to Ferrovibrio denitrificans S3T. The genome of SYSU D60015T was 5.66 Mb in size with 68.2% of DNA G + C content. The low digital DNA-DNA hybridization (dDDH, 18.0%), average nucleotide identity (ANI, 77.5%) and amino acid identity (AAI, 56.0%) values between SYSU D60015T and Ferrovibrio terrae K5T indicated that SYSU D60015T might represent a distinct genus. Based on the phylogenetic, phenotypic, chemotaxonomic and genomic data, we propose Desertibaculum subflavum gen. nov., sp. nov. as a novel species of a new genus within the family Sneathiellaceae. The type strain is SYSU D60015T (= NBRC 112952T = CGMCC 1.16256T).
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Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano , Clima Desértico , Ácidos Grasos , Filogenia , ARN Ribosómico 16S , Microbiología del Suelo , ARN Ribosómico 16S/genética , ADN Bacteriano/genética , China , Ácidos Grasos/análisis , Ácidos Grasos/química , Análisis de Secuencia de ADN , Fosfolípidos/análisis , Fosfolípidos/químicaRESUMEN
BACKGROUND: Megakaryocytic differentiation is a complicated process regulated by a series of transcription factors in a context- and stage-dependent manner. Recent studies have suggested that krüppel-like transcription factor 2 (KLF2) is involved in the control of embryonic erythroid precursor cell differentiation and maturation. However, the function and mechanism of KLF2 in regulating megakaryocytic differentiation remain unclear. METHODS: The expression patterns of krüppel-like transcription factors (KLFs) during megakaryocytic differentiation were identified from public databases. Phorbol 12-myristate 13-acetate (PMA) treatment of the myeloid-erythroid-leukemic cell lines K562 and HEL were used as cellular megakaryocytic differentiation models. A lentiviral transduction system was utilized to achieve the goal of amplifying or reducing KLF2. The expression of KLF2 was examined using real-time PCR and western blot. The impact of KLF2 on the megakaryocytic differentiation of K562 cells was examined by flow cytometry, Giemsa staining, Phalloidin staining and western blot. RNA-sequencing (RNA-seq) and chromatin immunoprecipitation-sequencing (ChIP-seq) technologies were used to identify the KLF2-regulated targets. RESULTS: KLF2 is increased in the maturation process of megakaryocytes. KLF2 overexpression accelerated the PMA-induced megakaryocytic differentiation, as reflected by an increased percentage of CD41/CD61 cells, an increased number of polyploid cells, and an elevated expression of P21 and P27. KLF2 knockdown exhibited the opposite results, indicating that KLF2 knockdown suppressed the megakaryocytic differentiation. Further, combination of the RNA-seq and ChIP-seq results suggested that chimerin 1 (CHN1) and potassium voltage-gated channel subfamily Q member 5 (KCNQ5) may be target genes regulated of KLF2. Both CHN1 and KCNQ5 knockdown could block the megakaryocytic differentiation to some content. CONCLUSION: This study implicated a regulatory role of KLF2 in megakaryocytic differentiation, which may suggest KLF2 as a target for illness with abnormal megakaryocytic differentiation.
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Taraxacum kok-saghyz (TKS) is a model plant and a potential rubber-producing crop for the study of natural rubber (NR) biosynthesis. The precise analysis of the NR biosynthesis mechanism is an important theoretical basis for improving rubber yield. The small rubber particle protein (SRPP) and rubber elongation factor (REF) are located in the membrane of rubber particles and play crucial roles in rubber biosynthesis. However, the specific functions of the SRPP/REF gene family in the rubber biosynthesis mechanism have not been fully resolved. In this study, we performed a genome-wide identification of the 10 TkSRPP and 2 TkREF genes' family members of Russian dandelion and a comprehensive investigation on the evolution of the ethylene/methyl jasmonate-induced expression of the SRPP/REF gene family in TKS. Based on phylogenetic analysis, 12 TkSRPP/REFs proteins were divided into five subclades. Our study revealed one functional domain and 10 motifs in these proteins. The SRPP/REF protein sequences all contain typical REF structural domains and belong to the same superfamily. Members of this family are most closely related to the orthologous species T. mongolicum and share the same distribution pattern of SRPP/REF genes in T. mongolicum and L. sativa, both of which belong to the family Asteraceae. Collinearity analysis showed that segmental duplication events played a key role in the expansion of the TkSRPP/REFs gene family. The expression levels of most TkSRPP/REF members were significantly increased in different tissues of T. kok-saghyz after induction with ethylene and methyl jasmonate. These results will provide a theoretical basis for the selection of candidate genes for the molecular breeding of T. kok-saghyz and the precise resolution of the mechanism of natural rubber production.
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Acetatos , Ciclopentanos , Etilenos , Regulación de la Expresión Génica de las Plantas , Familia de Multigenes , Oxilipinas , Filogenia , Proteínas de Plantas , Taraxacum , Oxilipinas/farmacología , Ciclopentanos/farmacología , Taraxacum/genética , Taraxacum/metabolismo , Taraxacum/efectos de los fármacos , Etilenos/farmacología , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Acetatos/farmacología , Genoma de Planta , Estudio de Asociación del Genoma CompletoRESUMEN
The Activator Protein 1 (AP-1) transcription factor complex plays a pivotal role in the regulation of cancer-related genes, influencing cancer cell proliferation, invasion, migration, angiogenesis, and apoptosis. Composed of multiple subunits, AP-1 has diverse roles across different cancer types and environmental contexts, but its specific mechanisms remain unclear. The advent of multi-omics approaches has shed light on a more comprehensive understanding of AP-1's role and mechanism in gene regulation. This review collates recent genome-wide data on AP-1 and provides an overview of its expression, structure, function, and interaction across different diseases. An examination of these findings can illuminate the intricate nature of AP-1 regulation and its significant involvement in the progression of different diseases. Moreover, we discuss the potential use of AP-1 as a target for individual therapy and explore the various challenges associated with such an approach. Ultimately, this review provides valuable insights into the biology of AP-1 and its potential as a therapeutic target for cancer and disease treatments.
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The type III-A (Csm) CRISPR-Cas systems are multi-subunit and multipronged prokaryotic enzymes in guarding the hosts against viral invaders. Beyond cleaving activator RNA transcripts, Csm confers two additional activities: shredding single-stranded DNA and synthesizing cyclic oligoadenylates (cOAs) by the Cas10 subunit. Known Cas10 enzymes exhibit a fascinating diversity in cOA production. Three major forms-cA3, cA4 and cA6have been identified, each with the potential to trigger unique downstream effects. Whereas the mechanism for cOA-dependent activation is well characterized, the molecular basis for synthesizing different cOA isoforms remains unclear. Here, we present structural characterization of a cA6-producing Csm complex during its activation by an activator RNA. Analysis of the captured intermediates of cA6 synthesis suggests a 3'-to-5' nucleotidyl transferring process. Three primary adenine binding sites can be identified along the chain elongation path, including a unique tyrosine-threonine dyad found only in the cA6-producing Cas10. Consistently, disrupting the tyrosine-threonine dyad specifically impaired cA6 production while promoting cA4 production. These findings suggest that Cas10 utilizes a unique enzymatic mechanism for forming the phosphodiester bond and has evolved distinct strategies to regulate the cOA chain length.
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Microplastic records from lake cores can reconstruct the plastic pollution history. However, the associations between anthropogenic activities and microplastic accumulation are not well understood. Huguangyan Maar Lake (HML) is a deep-enclosed lake without inlets and outlets, where the sedimentary environment is ideal for preserving a stable and historical microplastic record. Microplastic (size: 10-500 µm) characteristics in the HML core were identified using the Laser Direct Infrared Imaging system. The earliest detectable microplastics appeared unit in 1955 (1.1 items g-1). The microplastic abundance ranged from n.d. to 615.2 items g-1 in 1955-2019 with an average of 134.9 items g-1. The abundance declined slightly during the 1970s and then increased rapidly after China's Reform and Opening Up in 1978. Sixteen polymer types were detectable, with polyethylene and polypropylene dominating, accounting for 23.5 and 23.3% of the total abundance, and the size at 10-100 µm accounted for 80%. Socioeconomic factors dominated the microplastic accumulation based on the random forest modeling, and the contributions of GDP per capita, plastic-related industry yield, and total crop yield were, respectively, 13.9, 35.1, and 9.3% between 1955-2019. The total crop yield contribution further increased by 1.7% after 1978. Coarse sediment particles increased with soil erosion exacerbated microplastics discharging into the sediment.
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Monitoreo del Ambiente , Lagos , Microplásticos , China , Microplásticos/análisis , Contaminantes Químicos del Agua/análisis , Plásticos , Sedimentos Geológicos/químicaRESUMEN
BBX protein is a class of zinc finger transcription factors that have B-box domains at the N-terminus, and some of these proteins contain a CCT domain at the C-terminus. It plays an important role in plant growth, development, and metabolism. However, the expression pattern of BBX genes in alfalfa under hormonal and salt stresses is still unclear. In this study, we identified a total of 125 BBX gene family members by the available Medicago reference genome in diploid alfalfa (Medicago sativa spp. Caerulea), a model plant (M. truncatula), and tetraploid alfalfa (M. sativa), and divided these members into five subfamilies. We found that the conserved motifs of BBXs of the same subfamily reveal similarities. We analyzed the collinearity relationship and duplication mode of these BBX genes and found that the expression pattern of BBX genes is specific in different tissues. Analysis of the available transcriptome data suggests that some members of the BBX gene family are involved in multiple abiotic stress responses, and the highly expressed genes are often clustered together. Furthermore, we identified different expression patterns of some BBX genes under salt, ethylene, salt and ethylene, salicylic acid, and salt and salicylic acid treatments, verified by qRT-PCR, and analyzed the subcellular localization of MsBBX2, MsBBX17, and MsBBX32 using transient expression in tobacco. The results showed that BBX genes were localized in the nucleus. This study systematically analyzed the BBX gene family in Medicago plants, which provides a basis for the study of BBX gene family tolerance to abiotic stresses.
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Regulación de la Expresión Génica de las Plantas , Familia de Multigenes , Filogenia , Proteínas de Plantas , Estrés Salino , Factores de Transcripción , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estrés Salino/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Genoma de Planta , Medicago sativa/genética , Medicago sativa/metabolismo , Medicago sativa/efectos de los fármacos , Medicago/genética , Reguladores del Crecimiento de las Plantas/farmacología , Reguladores del Crecimiento de las Plantas/metabolismo , Perfilación de la Expresión Génica , Estudio de Asociación del Genoma Completo , Estrés Fisiológico/genéticaRESUMEN
Combinations of UV with oxidants can initiate advanced oxidation processes (AOPs) and enhance bacterial inactivation. However, the effectiveness and mechanisms of UV-AOPs in damaging nucleic acids (e.g., antibiotic resistance genes (ARGs)) and cell integrity represent a knowledge gap. This study comprehensively compared ARG degradation and cell membrane damage under three different UV-AOPs. The extracellular ARG (eARG) removal efficiency followed the order of UV/chlorine > UV/H2O2 > UV/peracetic acid (PAA). Hydroxyl radical (â¢OH) and reactive chlorine species (RCS) largely contributed to eARG removal, while organic radicals made a minor contribution. For intracellular ARGs (iARGs), UV/H2O2 did not remove better than UV alone due to the scavenging of â¢OH by cell components, whereas UV/PAA provided a modest synergism, likely due to diffusion of PAA into cells and intracellular â¢OH generation. Comparatively, UV/chlorine achieved significant synergistic iARG removal, suggesting the critical role of the RCS in resisting cellular scavenging and inactivating ARGs. Additionally, flow cytometry analysis demonstrated that membrane damage was mainly attributed to chlorine oxidation, while the impacts of radicals, H2O2, and PAA were negligible. These results provide mechanistic insights into bacterial inactivation and fate of ARGs during UV-AOPs, and shed light on the suitability of quantitative polymerase chain reaction (qPCR) and flow cytometry in assessing disinfection performance.
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Recent advancements in large language models (LLMs) such as ChatGPT and LLaMA have hinted at their potential to revolutionize medical applications, yet their application in clinical settings often reveals limitations due to a lack of specialized training on medical-specific data. In response to this challenge, this study introduces Me-LLaMA, a novel medical LLM family that includes foundation models - Me-LLaMA 13/70B, along with their chat-enhanced versions - Me-LLaMA 13/70B-chat, developed through continual pre-training and instruction tuning of LLaMA2 using large medical datasets. Our methodology leverages a comprehensive domain-specific data suite, including a large-scale, continual pre-training dataset with 129B tokens, an instruction tuning dataset with 214k samples, and a new medical evaluation benchmark (MIBE) across six critical medical tasks with 12 datasets. Our extensive evaluation using the MIBE shows that Me-LLaMA models achieve overall better performance than existing open-source medical LLMs in zero-shot, few-shot and supervised learning abilities. With task-specific instruction tuning, Me-LLaMA models outperform ChatGPT on 7 out of 8 datasets and GPT-4 on 5 out of 8 datasets. In addition, we investigated the catastrophic forgetting problem, and our results show that Me-LLaMA models outperform other open-source medical LLMs in mitigating this issue. Me-LLaMA is one of the largest open-source medical foundation LLMs that use both biomedical and clinical data. It exhibits superior performance across both general and medical tasks compared to other open-source medical LLMs, rendering it an attractive choice for medical AI applications. We release our models, datasets, and evaluation scripts at: https://github.com/BIDS-Xu-Lab/Me-LLaMA.
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Degradation of target proteins has been considered to be a promising therapeutic approach, but the rational design of compounds for degradation remains a challenge. In this study, we reasonably designed and synthesized only 10 compounds to discover effective CDK4/6 protein degraders. Among the newly synthesized compounds, 7f achieved dual degradation of CDK4/6 protein, with DC50 values of 10.5 and 2.5 nM, respectively. Compound 7f also exhibited inhibitory proliferative activity against Jurkat cells with an IC50 value of 0.18 µM. Furthermore, 7f induced cell apoptosis and G1 phase cell cycle arrest in a dose-dependent manner in Jurkat cells. In conclusion, these findings demonstrate the potential of 7f as a CDK4/6 degrader and a potential therapeutic strategy against cancer, thereby expanding the potential of CDK4/6 dual PROTACs.
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Antineoplásicos , Apoptosis , Proliferación Celular , Quinasa 4 Dependiente de la Ciclina , Quinasa 6 Dependiente de la Ciclina , Diseño de Fármacos , Humanos , Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 4 Dependiente de la Ciclina/metabolismo , Quinasa 6 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 6 Dependiente de la Ciclina/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Proliferación Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/síntesis química , Células Jurkat , Relación Estructura-Actividad , Proteolisis/efectos de los fármacos , Estructura MolecularAsunto(s)
Antineoplásicos , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Diseño Asistido por Computadora , Relación Dosis-Respuesta a Droga , Diseño de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/síntesis química , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Colorantes Fluorescentes/farmacología , N-Metiltransferasa de Histona-Lisina/antagonistas & inhibidores , N-Metiltransferasa de Histona-Lisina/metabolismo , Estructura Molecular , Relación Estructura-Actividad , Mutaciones Letales Sintéticas , Metionina Adenosiltransferasa/antagonistas & inhibidores , Metionina Adenosiltransferasa/química , Metionina Adenosiltransferasa/metabolismoRESUMEN
The consistent and persuasive evidence illustrating the influence of social determinants on health has prompted a growing realization throughout the health care sector that enhancing health and health equity will likely depend, at least to some extent, on addressing detrimental social determinants. However, detailed social determinants of health (SDoH) information is often buried within clinical narrative text in electronic health records (EHRs), necessitating natural language processing (NLP) methods to automatically extract these details. Most current NLP efforts for SDoH extraction have been limited, investigating on limited types of SDoH elements, deriving data from a single institution, focusing on specific patient cohorts or note types, with reduced focus on generalizability. This study aims to address these issues by creating cross-institutional corpora spanning different note types and healthcare systems, and developing and evaluating the generalizability of classification models, including novel large language models (LLMs), for detecting SDoH factors from diverse types of notes from four institutions: Harris County Psychiatric Center, University of Texas Physician Practice, Beth Israel Deaconess Medical Center, and Mayo Clinic. Four corpora of deidentified clinical notes were annotated with 21 SDoH factors at two levels: level 1 with SDoH factor types only and level 2 with SDoH factors along with associated values. Three traditional classification algorithms (XGBoost, TextCNN, Sentence BERT) and an instruction tuned LLM-based approach (LLaMA) were developed to identify multiple SDoH factors. Substantial variation was noted in SDoH documentation practices and label distributions based on patient cohorts, note types, and hospitals. The LLM achieved top performance with micro-averaged F1 scores over 0.9 on level 1 annotated corpora and an F1 over 0.84 on level 2 annotated corpora. While models performed well when trained and tested on individual datasets, cross-dataset generalization highlighted remaining obstacles. To foster collaboration, access to partial annotated corpora and models trained by merging all annotated datasets will be made available on the PhysioNet repository.
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This study employed a two-step hydrothermal reduction process and freeze-drying technique. Initially, carbon nanosphere composite aerogels (CNSs) were synthesized through the hydrothermal reduction of glucose. Subsequently, boron-doped graphene/carbon nanosphere composite aerogel (BGA/CNS) was prepared by utilizing graphene oxide (GO) and boric acid as carbon (C) and boron (B) sources, respectively, in conjunction with CNS. The photo-enhanced thermionic electron emission (PETE) performance of the samples was assessed using a custom-made device. Boron atom doping was found to modulate the bandgap of graphene aerogel and induce P-type semiconductor characteristics, while the addition of CNSs increased its specific surface area, thereby enhancing its photoelectric properties. The results indicated that BGA/CNS-8h exhibited superior PETE effects, with a short-circuit current, open-circuit voltage, and maximum power of 5.81 µA, -2.10V, and-1.57µW.
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Nitrogen-fixing cyanobacteria not only cause severe blooms but also play an important role in the nitrogen input processes of lakes. The production of extracellular polymeric substances (EPS) and the ability to fix nitrogen from the atmosphere provide nitrogen-fixing cyanobacteria with a competitive advantage over other organisms. Temperature and nitrogen availability are key environmental factors in regulating the growth of cyanobacteria. In this study, Dolichospermum (formerly known as Anabaena) was cultivated at three different temperatures (10 °C, 20 °C, and 30 °C) to examine the impact of temperature and nitrogen availability on nitrogen fixation capacity and the release of EPS. Initially, confocal laser scanning microscopy (CLSM) and the quantification of heterocysts at different temperatures revealed that lower temperatures (10 °C) hindered the differentiation of heterocysts under nitrogen-deprived conditions. Additionally, while heterocysts inhibited the photosynthetic activity of Dolichospermum, the secretion of EPS was notably affected by nitrogen limitation, particularly at 30 °C. Finally, real-time quantitative polymerase chain reaction (qPCR) was used to measure the expression of nitrogen-utilizing genes (ntcA and nifH) and EPS synthesis-related genes (wzb and wzc). The results indicated that under nitrogen-deprived conditions, the expression of each gene was upregulated, and there was a significant correlation between the upregulation of nitrogen-utilizing and EPS synthesis genes (P < 0.05). Our findings suggested that Dolichospermum responded to temperature variation by affecting the formation of heterocysts, impacting its potential nitrogen fixation capacity. Furthermore, the quantity of EPS released was more influenced by nitrogen availability than temperature. This research enhances our comprehension of interconnections between nitrogen deprivation and EPS production under the different temperatures.