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The blue emission-dominated NaYbF4@NaYF4:2%Ho@NaYF4 (CSS) upconversion nanoparticles (UCNPs) were designed to detect ascorbic acid (AA). The blue emission of CSS was increased, ∼34 and ∼8 times higher than that of NaYF4:2%Ho@NaYbF4@NaYF4 (CSS (I)) and NaYbF4@NaYF4:20%Yb,2%Ho@ NaYF4 (CSS (II)), respectively. The dominant blue emission of CSS might be attributed to three aspects: (1) the protected NaYbF4 core for high near-infrared absorption, (2) the spatial separation of Yb3+ and Ho3+ preventing back energy transfer, and (3) their inert shell inhibiting surface quenching. It is worth noting that the fluorescence resonance energy transfer (FRET) of the CSS (donor) to MnO2 nanosheets (acceptor) was developed to trace AA. The detection limit is 0.75 µM and the detection range is 0.5-100 µM. In summary, our work not only explored the blue emission mechanism of Ho3+, but also constructed a CSS/MnO2-based nanosensing platform for the rapid and sensitive detection of AA. The blue emission of Ho3+ has promising applications in the field of sensing and detection.

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Plants adapt to cold stress through a tightly regulated process involving metabolic reprogramming and tissue remodeling to enhance tolerance within a short timeframe. However, the precise differences and interconnections among various organs during cold adaptation remain poorly understood. This study employed dynamic transcriptomic and metabolite quantitative analyses to investigate cold adaptation and subsequent de-adaptation in Artemisia annua, a species known for its robust resistance to abiotic stress. Our findings revealed distinct expression patterns in most differentially expressed genes (DEGs) encoding transcription factors and components of the calcium signal transduction pathway within the two organs under cold stress. Notably, the long-distance transport of carbon sources from source organs (leaves) to sink organs (roots) experienced disruption followed by resumption, while nitrogen transport from roots to leaves, primarily in the form of amino acids, exhibited acceleration. These contrasting transport patterns likely contribute to the observed differences in cold response between the two organs. The transcriptomic analysis further indicated that leaves exhibited increased respiration, accumulated anti-stress compounds, and initiated the ICE-CBF-COR signaling pathway earlier than roots. Differential expression of genes associated with cell wall biosynthesis suggests that leaves may undergo cell wall thickening while roots may experience thinning. Moreover, a marked difference was observed in phenylalanine metabolism between the two organs, with leaves favoring lignin production and roots favoring flavonoid synthesis. Additionally, our findings suggest that the circadian rhythm is crucial in integrating temperature fluctuations with the plant's internal rhythms during cold stress and subsequent recovery. Collectively, these results shed light on the coordinated response of different plant organs during cold adaptation, highlighting the importance of inter-organ communication for successful stress tolerance.

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A one-step logical analysis of multiple targets remains challenging. Herein, we report a one-pot and intelligent DNA logical analysis platform for the diagnosis of avian influenza virus (AIV) biomarkers based on chemiluminescence resonance energy transfer (CRET) and logic operations. On the surface of Lum/PEI/CaCO3 microparticles, the excited state of luminol underwent CRET with fluorescein isothiocyanate or rhodamine B isothiocyanate, producing three well-separated light emissions at 425, 530, and 590 nm, respectively. Taking advantage of the close distance between fluorophores aligned by the catalytic hairpin assembly reaction, the CRET efficiency was greatly enhanced (53.1%). H1N1, H7N9, and H5N1 were detected with limits of detection values as low as 15, 34, and 58 pM, respectively. Three-input logic circuits were simultaneously conducted on the surface of Lum/PEI/CaCO3 microparticles, enabling the rapid and accurate discrimination of multiple AIV biomarkers in one solution. In terms of peak positions and the normalized value of the total peak intensity, three biomarkers can be simultaneously discriminated without any other complex operations. In summary, the CRET-based multiple analytical assay was developed as an intelligent biosensor for identifying AIV biomarkers, having promising application prospects in the field of multiple analysis and precise disease diagnosis.

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Ferroptosis is a newly defined form of programmed cell death characterized by iron-dependent lipid peroxide accumulation and is associated with the progression of cancer. Solute carrier family 7 member 11 (SLC7A11), a key component of cystine/glutamate antiporter, has been characterized as a critical regulator of ferroptosis. Although many studies have established the transcriptional regulation of SLC7A11, it remains largely unknown how the stability of SLC7A11 is regulated in cancers, especially in triple-negative breast cancer (TNBC). Here we demonstrated that ovarian tumor domain-containing protein 5 (OTUD5), which deubiquitinated and stabilized SLC7A11, played a key role in TNBC progression and paclitaxel chemosensitivity through modulating ferroptosis. The clinical data analysis showed OTUD5 was higher expressed in TNBC, which positively correlated with SLC7A11 level. Mechanistically, OTUD5 interacted with SLC7A11 and cleaved K48-linked polyubiquitin chains from SLC7A11 to enhance the stability of SLC7A11. Taken together, these findings uncover a functional and mechanistic role of OTUD5 in TNBC progression and paclitaxel sensitivity, indicating OTUD5 could be a potential target for TNBC treatment.

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In China, urban sprawl and developed land expansion challenge the country's "carbon peak" and "carbon neutrality" goals. Counties as the basic governance units are crucial for effective carbon reduction policies. This study examines land use carbon emissions (LUCE) in Shaanxi Province at the county level, essential for China's low-carbon strategy. Analyzing data from 107 counties between 2000 and 2020, we found that developed land, though increasing, is the primary carbon source with a slowing growth rate. The Conversion of Cropland to Forests and Grasslands national policy mitigated the impact on carbon absorption. Carbon emissions displayed positive autocorrelation and spatial heterogeneity, varying across the region. Using the Spatial Durbin Error Model, we linked county-level emissions to GDP per capita, population, urbanization rate, and research and development expenditure for direct and indirect influence. These factors correlate with fossil fuel use and high-quality industrial development. Promoting public transits and reducing private car use are vital for achieving local and regional low-carbon goals.

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Catheter ablation (CA) is an essential method for the interventional treatment of atrial fibrillation (AF), and it is very important to reduce long-term recurrence after CA. The mechanism of recurrence after CA is still unclear. We established a long-term model of beagle canines after circumferential pulmonary vein ablation (CPVA). The transcriptome and proteome were obtained using high-throughput sequencing and TMT-tagged LC-MS/LC analysis, respectively. Differentially expressed genes and proteins were screened and enriched, and the effect of fibrosis was found and verified in tissues. A downregulated protein, neuropeptide Y (NPY), was selected for validation and the results suggest that NPY may play a role in the long-term reinduction of AF after CPVA. Then, the molecular mechanism of NPY was further investigated. The results showed that the atrial effective refractory period (AERP) was shortened and fibrosis was increased after CPVA. Atrial myocyte apoptosis was alleviated by NPY intervention, and Akt activation was inhibited in cardiac fibroblasts. These results suggest that long-term suppression of NPY after CPVA may lead to induction of AF through promoting cardiomyocyte apoptosis and activating the Akt pathway in cardiac fibroblasts, which may make AF more likely to reinduce.

Asunto(s)

Apoptosis , Fibrilación Atrial , Ablación por Catéter , Miocardio , Neuropéptido Y , Venas Pulmonares , Animales , Perros , Apoptosis/efectos de los fármacos , Fibrilación Atrial/metabolismo , Fibrilación Atrial/cirugía , Fibrilación Atrial/patología , Ablación por Catéter/métodos , Modelos Animales de Enfermedad , Fibrosis , Atrios Cardíacos/metabolismo , Atrios Cardíacos/patología , Multiómica , Miocardio/metabolismo , Miocardio/patología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Neuropéptido Y/metabolismo , Proteoma/metabolismo , Proteómica/métodos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Venas Pulmonares/metabolismo , Venas Pulmonares/cirugía , Transcriptoma

RESUMEN

BACKGROUND: Nucleophosmin 1 (NPM1) gene-mutated acute myeloid leukemia (NPM1mut AML) is classified as a subtype with a favorable prognosis. However, some patients fail to achieve a complete remission or relapse after intensified chemotherapy. Genetic abnormalities in concomitant mutations contribute to heterogeneous prognosis of NPM1mut AML patients. METHODS: In this study, 91 NPM1-mutated and FLT3-ITD wild-type (NPM1mut/FLT3-ITDwt) AML patients with intermediate-risk karyotype were enrolled to analyze the impact of common genetic co-mutations on chemotherapeutic outcome. RESULTS: Our data revealed that TET1/2 (52/91, 57.1%) was the most prevalent co-mutation in NPM1mut AML patients, followed by IDH1/2 (36/91, 39.6%), DNMT3A (35/91, 38.5%), myelodysplastic syndrome related genes (MDS-related genes) (ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1 and ZRSR2 genes) (35/91, 38.5%), FLT3-TKD (27/91, 29.7%) and GATA2 (13/91, 14.3%) mutations. Patients with TET1/2mut exhibited significantly worse relapse-free survival (RFS) (median, 28.7 vs. not reached (NR) months; p = 0.0382) compared to patients with TET1/2wt, while no significant difference was observed in overall survival (OS) (median, NR vs. NR; p = 0.3035). GATA2mut subtype was associated with inferior OS (median, 28 vs. NR months; p < 0.0010) and RFS (median, 24 vs. NR months; p = 0.0224) compared to GATA2wt. By multivariate analysis, GATA2mut and MDS-related genesmut were independently associated with worse survival. CONCLUSION: Mutations in TET1/2, GATA2 and MDS-related genes were found to significantly influence the chemotherapeutic outcome of patients with NPM1mut AML. The findings of our study have significant clinical implications for identifying patients who have an adverse response to frontline chemotherapy and provide a novel reference for further prognostic stratification of NPM1mut/FLT3-ITDwt AML patients.

Asunto(s)

Leucemia Mieloide Aguda , Mutación , Proteínas Nucleares , Nucleofosmina , Tirosina Quinasa 3 Similar a fms , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/mortalidad , Femenino , Masculino , Persona de Mediana Edad , Proteínas Nucleares/genética , Adulto , Tirosina Quinasa 3 Similar a fms/genética , Anciano , Pronóstico , Adulto Joven , Resultado del Tratamiento , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico

RESUMEN

BACKGROUND: Approximately 25-30% of patients with acute myeloid leukemia (AML) have FMS-like receptor tyrosine kinase-3 (FLT3) mutations that contribute to disease progression and poor prognosis. Prolonged exposure to FLT3 tyrosine kinase inhibitors (TKIs) often results in limited clinical responses due to diverse compensatory survival signals. Therefore, there is an urgent need to elucidate the mechanisms underlying FLT3 TKI resistance. Dysregulated sphingolipid metabolism frequently contributes to cancer progression and a poor therapeutic response. However, its relationship with TKI sensitivity in FLT3-mutated AML remains unknown. Thus, we aimed to assess mechanisms of FLT3 TKI resistance in AML. METHODS: We performed lipidomics profiling, RNA-seq, qRT-PCR, and enzyme-linked immunosorbent assays to determine potential drivers of sorafenib resistance. FLT3 signaling was inhibited by sorafenib or quizartinib, and SPHK1 was inhibited by using an antagonist or via knockdown. Cell growth and apoptosis were assessed in FLT3-mutated and wild-type AML cell lines via Cell counting kit-8, PI staining, and Annexin-V/7AAD assays. Western blotting and immunofluorescence assays were employed to explore the underlying molecular mechanisms through rescue experiments using SPHK1 overexpression and exogenous S1P, as well as inhibitors of S1P2, ß-catenin, PP2A, and GSK3ß. Xenograft murine model, patient samples, and publicly available data were analyzed to corroborate our in vitro results. RESULTS: We demonstrate that long-term sorafenib treatment upregulates SPHK1/sphingosine-1-phosphate (S1P) signaling, which in turn positively modulates ß-catenin signaling to counteract TKI-mediated suppression of FLT3-mutated AML cells via the S1P2 receptor. Genetic or pharmacological inhibition of SPHK1 potently enhanced the TKI-mediated inhibition of proliferation and apoptosis induction in FLT3-mutated AML cells in vitro. SPHK1 knockdown enhanced sorafenib efficacy and improved survival of AML-xenografted mice. Mechanistically, targeting the SPHK1/S1P/S1P2 signaling synergizes with FLT3 TKIs to inhibit ß-catenin activity by activating the protein phosphatase 2 A (PP2A)-glycogen synthase kinase 3ß (GSK3ß) pathway. CONCLUSIONS: These findings establish the sphingolipid metabolic enzyme SPHK1 as a regulator of TKI sensitivity and suggest that combining SPHK1 inhibition with TKIs could be an effective approach for treating FLT3-mutated AML.

Asunto(s)

Glucógeno Sintasa Quinasa 3 beta , Leucemia Mieloide Aguda , Fosfotransferasas (Aceptor de Grupo Alcohol) , Proteína Fosfatasa 2 , beta Catenina , Tirosina Quinasa 3 Similar a fms , Tirosina Quinasa 3 Similar a fms/genética , Tirosina Quinasa 3 Similar a fms/metabolismo , Tirosina Quinasa 3 Similar a fms/antagonistas & inhibidores , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Glucógeno Sintasa Quinasa 3 beta/genética , beta Catenina/metabolismo , beta Catenina/genética , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Fosfotransferasas (Aceptor de Grupo Alcohol)/antagonistas & inhibidores , Animales , Ratones , Proteína Fosfatasa 2/metabolismo , Proteína Fosfatasa 2/genética , Proteína Fosfatasa 2/antagonistas & inhibidores , Línea Celular Tumoral , Sorafenib/farmacología , Apoptosis/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacología , Transducción de Señal/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Sinergismo Farmacológico , Ensayos Antitumor por Modelo de Xenoinjerto , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética

RESUMEN

The sluggish transition and shuttle of polysulfides (LiPS) significantly hinder the application and commercialization of Li-S batteries. Herein, carbon nanotubes (CNTs) supported 10 nm sized iron Hexadecafluorophthalocyanine (FePcF16/CNTs) are prepared using a solid synthesis approach. The well-exposed FePcF16 molecular improve the LiPS capture efficiency and redox kinetics by its central Fe-N4 units and F functional groups. The strong electron withdraw F groups significantly promote the conjugate effect and decrease the steric hindrance during mass migration procedure. Distribution of relaxation time (DRT) analysis shows that the Fe-N4 units exhibit strong affinity towards LiPS and the F groups further improve the Li+ diffusion rate in Li2S nucleation and oxidation procedure, accomplishing a porous surface on cathode. As a result, the FePcF16/CNTs separator exhibits a high initial capacity of 1136.2 mAh g-1 at 0.2 C, outstanding rate capacity of 624.9 mAh g-1 at 5 C and superior long-term stability at 2 C surviving 300 cycles with a low capacity decay of 0.43‰ per cycle.

RESUMEN

Biallelic mutations of the CEBPA gene (CEBPAbi) are generally associated with favorable prognosis in patients with acute myeloid leukemia (AML). Monoallelic mutations of the CEBPA gene in carboxy-terminal DNA-binding region (CEBPAsmbZIP) and amino-terminal transactivation domains (CEBPAsmTAD) indicate distinct clinical characteristics and therapeutic outcomes. However, further investigation is required to fully understand these differences. In this retrospective study, we enrolled 77 AML patients with CEBPA mutations, including 53 with CEBPAbi, 12 with CEBPAsmbZIP and 12 with CEBPAsmTAD. The clinical characteristics of the three CEBPAmut groups presented significant differences in age, FAB classification, hemoglobin level and platelet count at diagnosis. The CEBPAsmTAD group exhibited shorter 2-year overall survival (OS) and relapse-free survival (RFS) compared to the CEBPAbi group and CEBPAsmbZIP group in AML patients. The most common co-mutations observed in CEBPAmut AML patients were TET2 and GATA2, which had no effect on prognosis. 2-year RFS of 27 CEBPAmut AML patients who underwent allo-HSCT was better than those who did not. MRD3 positive was identified as an influencing factor for 2-year OS and RFS. Allo-HSCT was found to improve the prognosis of CEPBAmut AML patients with positive MRD3 and adverse co-mutations.

Asunto(s)

Proteínas Potenciadoras de Unión a CCAAT , Leucemia Mieloide Aguda , Mutación , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/diagnóstico , Proteínas Potenciadoras de Unión a CCAAT/genética , Masculino , Femenino , Persona de Mediana Edad , Adulto , Estudios Retrospectivos , Anciano , Trasplante de Células Madre Hematopoyéticas , Resultado del Tratamiento , Adulto Joven , Adolescente , Supervivencia sin Enfermedad , Pronóstico , Factor de Transcripción GATA2/genética , Tasa de Supervivencia

RESUMEN

Transcutaneous auricular vagus nerve stimulation (taVNS) is an emerging neuro modulation technology that has been reported to be beneficial in the treatment of diseases by several studies, but its exact mechanism of action is still unclear. It has been demonstrated that ta VNS can influence interoceptive signals. Notably, the processing of interoceptive signals is directly related to many diseases, such as depression, anxiety, and insomnia. The insula and the medial prefrontal cortex (MPFC) communicate during the bottom-up transmission of taVNS-induced signals, and both play a role in interoceptive signal processing. By focusing on the insula and MPFC, our research pioneers detail the potential interactions between interoceptive signal processing and the neuromodulation effects of taVNS, providing novel insights in to the neurobiological mechanisms of taVNS. Two functional connectivity (FC) analyses (region of interest-based and seed-based) were used in this study. We observed that negative connectivity between the insula and the MPFC was significantly weakened following taVNS, while there were no statistical changes in the sham group. Our findings elucidate potential mechanisms linking vagal activity with intrinsic FC among specific brain regions and networks. Specifically, our results indicate that taVNS may enhance the ability to flexibly balance interoceptive awareness and cognitive experiences by modulating the FC between the insula and MPFC. The modulation effects may impact body-brain interactions, suggesting the mechanism of taVNS in therapeutic applications.

RESUMEN

Major depressive disorder is a chronic mental health condition that seriously impacts afflicted individuals. Although electroacupuncture has proven to be an effective therapy for depression, its underlying biological mechanism remains largely unknown. In this study, we aimed to investigate the effects of electroacupuncture on depression-like behavior and to identify potential target genes related to those effects. To achieve this, we subjected rats to chronic unpredictable mild stress (CUMS) and used sucrose preference, forced swimming, and open-field tests to determine their depression-like behavior in the absence or after receipt of electroacupuncture treatment. RNA sequencing technology was then used to reveal the differentially expressed genes associated with depression and electroacupuncture treatment effects in the medial prefrontal cortex (mPFC). Repeated electroacupuncture treatments at the Baihui (GV20) and Taichong (LR3) acupoints significantly alleviated depression-like behavioral defects in the animals. Genomic RNA sequencing revealed several significant changes in the mPFC transcriptome of rats that received treatment. Through differential gene expression analysis, we found that electroacupuncture reversed the CUMS-induced downregulation of 46 genes and upregulation of 13 genes. Among the differentially expressed genes, Casr, Bdkrb2, Gnb3, and Ccl1 were found to be associated with depression and electroacupuncture treatment effects. In conclusion, we verified that electroacupuncture treatment has an effective antidepressant effect, and the underlying mechanism involves multiple systems and targets.

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The importance of sulfonyl-group-containing compounds, such as sulfonamides, sulfones, sulfinate esters, and sulfonyl fluorides, in pharmaceuticals, bioactive molecules, and natural products cannot be overstated. The new development of palladium-catalyzed sulfonylation via SO2 insertion represents a crucial advancement in organic synthesis, enabling the direct α,α-difunctionalization of SO2 and providing efficient access to an array of structure-diverse sulfonyl-containing compounds. Although there have been numerous reviews about SO2 insertion, many of them only cover specific aspects of palladium-catalyzed reactions, leading to an oversight of some important works. Besides, these reviews often lack detailed discussions and systematic conclusion on reaction mechanisms, and fail to comprehensively summarize the significant research achievements in palladium-catalyzed reactions over the past few years. Herein, we aim to systematically consolidate the recent advances in palladium-catalyzed sulfonylation via SO2 insertion, elucidate the underlying reaction mechanism, and highlight some unsolved challenges in this segment. This review seeks to serve as a valuable resource for researchers, assisting in the continued development of palladium-catalyzed sulfonylation methodologies.

RESUMEN

This study investigates the storage life of particle-filled polymer composites (PFPCs) under the influence of aging effects. High-temperature accelerated aging tests were conducted at 60 °C, 70 °C, and 80 °C for various days to analyze the impact of aging time and temperature on the mechanical behavior of the materials. A predictive model for crosslink density was established using the Arrhenius equation, and the relationship between crosslink density and relaxation modulus was determined based on polymer physics theory. On this basis, a viscoelastic constitutive model that incorporates aging effects was developed. Structural analyses of a PFPC column with a length of 2.3 m and outer diameter of 1.8 m were performed using the UMAT subroutine in ABAQUS. Subsequently, a safety margin assessment method based on dewetting strain was employed to predict the storage life of the PFPC column. The results indicate that the aging viscoelastic constitutive model effectively characterizes the hardening effects caused by aging in the composites during storage. The storage life for the PFPC column considering aging effects decreases from 22 years to 19 years compared to models that ignore such effects. This approach provides a reference for estimating the storage life of PFPC columns considering aging effects.

RESUMEN

To investigate the effects of different irrigation and nitrogen application modes on nitrogen gaseous loss in winter wheat farmland, we conducted a field experiment at Changqing Irrigation Experiment Station in Shandong Province, with two irrigation levels (80%-90% θf(I1) and 70%-80% θf(I2)) and three nitrogen application levels (conventional nitrogen application of 240 kg·hm-2(N1), nitrogen reduction of 12.5% (N2), and nitrogen reduction of 25% (N3)). The results showed that ammonia volatilization and nitrous oxide emission rate peak appeared within 2-4 days after fertilization or irrigation. The ammonia volatilization rate during the chasing fertilizer period was significantly higher than that during the basal fertilizer period. Compared with other treatments, the ave-rage ammonia volatilization rate of I2N2 treatment during the chasing fertilizer period was reduced by 10.1%-51.6%, and the average nitrous oxide emission rate over the whole growth period was reduced by 15.4%-52.2%. The ammonia volatilization rate was significantly positively associated with surface soil pH value and ammonium nitrogen content, while the nitrous oxide emission rate was significantly positively associated with nitrate content in topsoil. The accumulation amount of soil ammonia volatilization and nitrous oxide emission ranged from 0.83-1.42 and 0.11-0.33 kg·hm-2, respectively. Moderate reduction of irrigation water and nitrogen input could effectively reduce cumulative amounts of ammonia volatilization and nitrous oxide emission from winter wheat farmland. The cumulative amounts of ammonia volatilization and nitrous oxide emission under I1N3 and I2N2 treatments were signi-ficantly lower than those under other treatments. The highest winter wheat yield (5615.6 kg·hm-2) appeared in I2N2 treatment. The irrigation water utilization efficiency of I2 was significantly higher than that of I1, with the maximum increase rate of 45.2%. Compared with N1 and N3 treatments, the maximum increase rate of nitrogen fertilizer productivity and agricultural utilization efficiency in N2 reached 15.2% and 31.8%, respectively. In conclusion, the treatment with 70%-80% θf irrigation level and 210 kg·hm-2 nitrogen input could effectively improve the utilization efficiency of irrigation water and nitrogen fertilization and reduce gaseous loss from winter wheat farmland.

Asunto(s)

Amoníaco , Fertilizantes , Nitrógeno , Óxido Nitroso , Triticum , Agua , Triticum/crecimiento & desarrollo , Triticum/metabolismo , Óxido Nitroso/análisis , Óxido Nitroso/metabolismo , Nitrógeno/análisis , Nitrógeno/metabolismo , Amoníaco/análisis , Amoníaco/metabolismo , China , Agua/análisis , Agua/metabolismo , Riego Agrícola/métodos , Estaciones del Año , Biomasa , Suelo/química

RESUMEN

Multiplex detection can enhance diagnostic precision and improve diagnostic efficiency, providing important assistance for epidemiological investigation and epidemic prevention. There is a great need for multi-detection sensing platforms to accurately diagnose diseases. Herein, we reported a µPAD-based chemiluminescence (CL) assay for ultrasensitive multiplex detection of AIV biomarkers, based on three DNAzyme/Lum/PEI/CaCO3. Three time-resolved CL signals were sequentially generated with detection limits of 0.32, 0.34, and 0.29 pM for H1N1, H7N9, and H5N1, respectively, and with excellent selectivity against interfering DNA. The recovery test in human serum displayed satisfactory analysis capabilities for complex biological samples. The µPAD-based CL assay achieved multiplex detection within 70 s, with a high time resolution of 20 s. The proposed strategy has the advantages of low cost, high sensitivity, good selectivity, and wide time resolution, the µPAD-based CL assay has shown great potential in the early and accurate diagnosis of diseases.

Asunto(s)

Biomarcadores , Mediciones Luminiscentes , Mediciones Luminiscentes/métodos , Humanos , Biomarcadores/sangre , Biomarcadores/análisis , Papel , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Subtipo H5N1 del Virus de la Influenza A/aislamiento & purificación , Subtipo H5N1 del Virus de la Influenza A/genética , Subtipo H7N9 del Virus de la Influenza A/aislamiento & purificación , Subtipo H7N9 del Virus de la Influenza A/genética , Animales , Gripe Aviar/diagnóstico , Gripe Aviar/virología , ADN Catalítico/química , ADN Catalítico/metabolismo , Aves/virología , Límite de Detección , Gripe Humana/diagnóstico , Gripe Humana/virología , Técnicas Analíticas Microfluídicas/métodos , Técnicas Analíticas Microfluídicas/instrumentación

RESUMEN

Ferrate (Fe(VI)) is an environmentally friendly disinfectant that is widely used to eradicate microbes in reclaimed water. However, the potential health risks associated with inhalation of Fe(VI)-treated bacteria-laden reclaimed water remains uncertain. We aimed to explore the inhalation hazards and potential mechanisms of K2FeO4-treated Escherichia coli (E. coli, ATCC 25922). Our findings indicated that Fe(VI) disinfection induced a dose- and time-dependent E. coli inactivation, accompanied by a rapid release of the bacterial endotoxin, lipopolysaccharide (LPS). Scanning electron microscopy (SEM) observations indicate that Fe(VI)-induced endotoxin production consists of at least two stages: initial binding of endotoxin to bacteria and subsequent dissociation to release free endotoxin. Furthermore, Fe(VI) disinfection was not able to effectively eliminate pure or E. coli-derived endotoxins. The E. coli strain used in this study lacks lung infection capability, thus the inhalation of bacteria alone failed to induce severe lung injury. However, mice inhaled exposure to Fe(VI)-treated E. coli showed severe impairment of lung structure and function. Moreover, we observed an accumulation of neutrophil/macrophage recruitment, cell apoptosis, and ROS generation in the lung tissue of mice subjected to Fe(VI)-treated E. coli. RNA sequencing (RNA-seq) and PCR results revealed that genes involved with endotoxin stimuli, cell apoptosis, antioxidant defence, inflammation response, chemokines and their receptors were upregulated in response to Fe(VI)-treated E. coli. In conclusion, Fe(VI) is ineffective in eliminating endotoxins and can trigger secondary hazards owing to endotoxin release from inactivated bacteria. Aerosol exposure to Fe(VI)-treated E. coli causes considerable damage to lung tissue by inducing oxidative stress and inflammatory responses.

Asunto(s)

Endotoxinas , Escherichia coli , Inflamación , Lesión Pulmonar , Estrés Oxidativo , Escherichia coli/efectos de los fármacos , Ratones , Animales , Lesión Pulmonar/inducido químicamente , Lesión Pulmonar/microbiología , Hierro/metabolismo , Desinfección/métodos , Desinfectantes/toxicidad

RESUMEN

Objectives: The study aimed to propose a multimodal model that incorporates both macroscopic and microscopic images and analyze its influence on clinicians' decision-making with different levels of experience. Methods: First, we constructed a multimodal dataset for five skin disorders. Next, we trained unimodal models on three different types of images and selected the best-performing models as the base learners. Then, we used a soft voting strategy to create the multimodal model. Finally, 12 clinicians were divided into three groups, with each group including one director dermatologist, one dermatologist-in-charge, one resident dermatologist, and one general practitioner. They were asked to diagnose the skin disorders in four unaided situations (macroscopic images only, dermatopathological images only, macroscopic and dermatopathological images, all images and metadata), and three aided situations (macroscopic images with model 1 aid, dermatopathological images with model 2&3 aid, all images with multimodal model 4 aid). The clinicians' diagnosis accuracy and time for each diagnosis were recorded. Results: Among the trained models, the vision transformer (ViT) achieved the best performance, with accuracies of 0.8636, 0.9545, 0.9673, and AUCs of 0.9823, 0.9952, 0.9989 on the training set, respectively. However, on the external validation set, they only achieved accuracies of 0.70, 0.90, and 0.94, respectively. The multimodal model performed well compared to the unimodal models, achieving an accuracy of 0.98 on the external validation set. The results of logit regression analysis indicate that all models are helpful to clinicians in making diagnostic decisions [Odds Ratios (OR) > 1], while metadata does not provide assistance to clinicians (OR < 1). Linear analysis results indicate that metadata significantly increases clinicians' diagnosis time (P < 0.05), while model assistance does not (P > 0.05). Conclusions: The results of this study suggest that the multimodal model effectively improves clinicians' diagnostic performance without significantly increasing the diagnostic time. However, further large-scale prospective studies are necessary.

RESUMEN

BACKGROUND: To investigate the effectiveness of the intervention with critical value management and push short messaging service (SMS), and to determine improvement in the referral rate of patients with positive hepatitis C antibody (anti-HCV). METHODS: No intervention was done for patients with positive anti-HCV screening results from 1 January 2015 to 31 October 2021. Patients with positive anti-HCV results at our hospital from 1 November 2021 to 31 July 2022 were informed vide critical value management and push SMS. For inpatients, a competent physician was requested to liaise with the infectious disease physician for consultation, and patients seen in the OPD (outpatient department) were asked to visit the liver disease clinic. The Chi-square correlation test, one-sided two-ratio test and linear regression were used to test the relationship between intervention and referral rate. RESULTS: A total of 638,308 cases were tested for anti-hepatitis C virus (HCV) in our hospital and 5983 of them were positive. 51.8% of the referred patients were aged 18-59 years and 10.8% were aged ≥75 years. The result of Chi-square correlation test between intervention and referral was p = .0000, p < .05. One-sided two-ratio test was performed for statistics of pre-intervention referral rate (p1) and post-intervention referral rate (p2). Normal approximation and Fisher's exact test for the results obtained were 0.000, p < .05, and the alternative hypothesis p1 - p2 < 0 was accepted. The linear regression equation was referral = 0.1396 × intervention + 0.3743, and the result model p = 8.79e - 09, p < .05. The model was significant, and the coefficient of intervention was 0.1396. CONCLUSIONS: The interventions of critical value management and push SMS were correlated with the referral rate of patients with positive anti-HCV.

Asunto(s)

Hepatitis C , Derivación y Consulta , Humanos , Derivación y Consulta/estadística & datos numéricos , Persona de Mediana Edad , Masculino , Femenino , Adulto , Anciano , Adolescente , Hepatitis C/tratamiento farmacológico , Hepatitis C/diagnóstico , Adulto Joven , Anticuerpos contra la Hepatitis C/sangre , Envío de Mensajes de Texto , Mejoramiento de la Calidad

RESUMEN

BACKGROUND: Patients with immunodeficiency virus-1 (HIV-1) infection are challenging to be cured completely due to the existence of HIV-1 latency reservoirs. However, the knowledge of the mechanisms and biomarkers associated with HIV-1 latency is limited. Therefore, identifying proteins related to HIV-1 latency could provide new insights into the underlying mechanisms of HIV-1 latency, and ultimately contribute to the eradication of HIV reservoirs. METHODS: An Isobaric Tags for Relative and Absolute Quantification (iTRAQ)-labeled subcellular proteomic study was performed on an HIV-1 latently infected cell model (U1, a HIV-1-integrated U937 cell line) and its control (U937). Differentially expressed proteins (DEPs) were analyzed using STRING-DB. Selected DEPs were further evaluated by western blotting and multiple reaction monitoring technology in both cell model and patient-derived cluster of differentiation 4 (CD4)+ T cells. Finally, we investigated the relationship between a specific DEP lysosome-associated membrane glycoprotein 2 (LAMP2) and HIV-1 reactivation by panobinostat or lysosome regulation by a lysosomotropic agent hydroxychloroquine in U1 and U937 cells. RESULTS: In total, 110 DEPs were identified in U1 cells comparing to U937 control cells. Bioinformatics analysis suggested associations of the altered proteins with the immune response and endosomal/lysosomal pathway. LAMP2, leukocyte surface antigen CD47, CD55, and ITGA6 were downregulated in HIV-1 latent cells. Downregulated LAMP2 was further confirmed in resting CD4+ T cells from patients with latent HIV-1 infection. Furthermore, both HIV-1 reactivation by panobinostat and stimulation with hydroxychloroquine upregulated LAMP2 expression. CONCLUSIONS: Our results indicated the involvement of the endosomal/lysosomal pathway in HIV-1 latency in macrophage cell model. The down-modulation of LAMP2 was associated with HIV latency, and the restoration of LAMP2 expression accompanied the transition of viral latency to active infection. This study provides new insights into the mechanism of HIV-1 latency and potential strategies for eradicating HIV-1 reservoirs by targeting LAMP2 expression.