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Olfactory functioning involves multiple cognitive processes and the coordinated actions of various neural systems. Any disruption at any stage of this process may result in olfactory dysfunction, which is consequently widely used to predict the onset and progression of diseases, such as Alzheimer's Disease (AD). Although the underlying mechanisms have not yet been fully unraveled, apparent changes were observed in olfactory brain areas form patients who suffer from AD by means of medical imaging and electroencephalography (EEG). Olfactory dysfunction holds significant promise in detecting AD during the preclinical stage preceding mild cognitive impairment (MCI). Owing to the strong specificity, olfactory tests are prevalently applied for screening in community cohorts. And combining olfactory tests with other biomarkers may further establish an optimal model for AD prediction in studies of specific olfactory dysfunctions and improve the sensitivity and specificity of early AD diagnosis.
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BACKGROUND: Liver cancer represents a most common and fatal cancer worldwide. Xianglian Pill (XLP) is an herbal formula holding great promise in clearing heat for treating diseases in an integrative and holistic way. However, due to the complex constituents and multiple targets, the exact molecular mechanisms of action of XLP are still unclear. PURPOSE: This study is focused on hepatocellular carcinoma (HCC), the most common type of liver cancer. The aim of this study is to develop a fast and efficient model to investigate the anti-HCC effects of XLP, and its underlying mechanisms. MATERIALS AND METHODS: HepG2, Hep3B, Mahlavu, HuH-7, or Li-7 cells were employed in the studies. The ingredients were analyzed using liquid chromatography tandem mass spectrometry (LC-MS). RNA sequencing combined with network pharmacology was used to elucidate the therapeutic mechanism of XLP in HCC via in silico and in vitro studies. An approach was constructed to improve the accuracy of prediction in network pharmacology by combining big data and omics. RESULTS: First, we identified 13 potential ingredients in the serum of XLP-administered rats using LC-MS. Then the network pharmacology was performed to predict that XLP demonstrates anti-HCC effects via targeting 94 genes involving in 13 components. Modifying the database thresholds might impact the accuracy of network pharmacology analysis based on RNA sequencing data. For instance, when the matching rate peak is 0.43, the correctness rate peak is 0.85. Moreover, 9 components of XLP and 6 relevant genes have been verified with CCK-8 and RT-qPCR assay, respectively. CONCLUSION: Based on the crossing studies of RNA sequencing and network pharmacology, XLP was found to improve HCC through multiple targets and pathways. Additionally, the study provides a way to optimize network pharmacology analysis in herbal medicine research.
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Single-nucleotide polymorphism (SNP) detection is critical for diagnosing diseases, and the development of rapid and accurate diagnostic tools is essential for treatment and prevention. Allele-specific polymerase chain reaction (AS-PCR) is widely used for detecting SNPs with multiplexing capabilities, while CRISPR-based technologies provide high sensitivity and specificity in targeting mutation sites through specific guide RNAs (gRNAs). In this study, we have integrated the high sensitivity and specificity of CRISPR technology with the multiplexing capabilities of AS-PCR, achieving the simultaneous detection of ten single-base mutations. As for Multi-AS-PCR, our research identified that competitive inhibition of primers targeting the same loci, coupled with divergent amplification efficiencies of these primers, could result in diminished amplification efficiency. Consequently, we adjusted and optimized primer combinations and ratios to enhance the amplification efficacy of Multi-AS-PCR. Finally, we successfully developed a novel nested Multi-AS-PCR-Cas12a method for multiplex SNPs detection. To evaluate the clinical utility of this method in a real-world setting, we applied it to diagnose rifampicin-resistant tuberculosis (TB). The limit of detection (LoD) for the nested Multi-AS-PCR-Cas12a was 102 aM, achieving sensitivity, specificity, positive predictive value, and negative predictive value of 100 %, 93.33 %, 90.00 %, and 100 %, respectively, compared to sequencing. In summary, by employing an innovative design that incorporates a universal reverse primer alongside ten distinct forward allele-specific primers, the nested Multi-AS-PCR-Cas12a technique facilitates the parallel detection of ten rpoB gene SNPs. This method also holds broad potential for the detection of drug-resistant gene mutations in infectious diseases and tumors, as well as for the screening of specific genetic disorders.
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Sistemas CRISPR-Cas , Polimorfismo de Nucleótido Simple , Sistemas CRISPR-Cas/genética , Humanos , Reacción en Cadena de la Polimerasa/métodos , Mutación , Mycobacterium tuberculosis/genética , Rifampin/farmacología , Límite de Detección , Reacción en Cadena de la Polimerasa Multiplex/métodos , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis Resistente a Múltiples Medicamentos/genética , Proteínas Bacterianas , Endodesoxirribonucleasas , Proteínas Asociadas a CRISPRRESUMEN
Post-stroke patients often experience psychological distress and autonomic nervous system (ANS) dysregulation, impacting their well-being. This study evaluated the effectiveness of heart rate variability (HRV) biofeedback on cognitive, motor, psychological, and ANS functions in sixty-two ischemic stroke patients (43 males, mean age = 60.1) at a Medical Center in southern Taiwan. To prevent interaction, we allocated patients to the HRV biofeedback or control (usual care) group based on their assigned rehabilitation days, with 31 patients in each group. Assessments conducted at baseline, three, and six months included the Montreal Cognitive Assessment (MoCA), Fugl-Meyer Assessment for Upper Extremities (FMA-UE), Perceived Stress Scale, Hospital Anxiety and Depression Scales (HADS), and HRV indices. Mixed-effect models were used to analyze Group by Time interactions. The results revealed significant interactions across all functions. At 3 months, significant improvements in the HRV biofeedback group were observed only in MoCA, FMA-UE, and HADS-depression scores compared to the control group. By 6 months, all measured outcomes demonstrated significant improvements in the biofeedback group relative to the control group. These results suggest that HRV biofeedback may be an effective complementary intervention in post-stroke rehabilitation, warranting further validation.
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In this work, ß-NiS nanoparticles (NPs) were efficiently prepared by a straightforward hydrothermal process. The difference in morphology between these NiS NPs was produced by adding different amounts of thiourea, and the corresponding products were denoted as NiS-15 and NiS-5. Through electrochemical tests, the specific capacity (Cs) of NiS-15 was determined to be 638.34 C g-1 at 1 A g-1, compared to 558.17 C g-1 for NiS-5. To explore the practical application potential of such ß-NiS NPs in supercapacitors, a hybrid supercapacitor (HSC) device was assembled with activated carbon (AC) as an anode. Benefitting from the high capacity of the NiS cathode and the large voltage window of the device, the NiS-15//AC HSC showed a high energy density (Ed) of 43.57 W h kg-1 at 936.92 W kg-1, and the NiS-5//AC HSC provided an inferior Ed of 37.89 W h kg-1 at 954.79 W kg-1. Both HSCs showed excellent cycling performance over 6000 cycles at 10 A g-1. The experimental findings suggest that both NiS-15 and NiS-5 in this study can serve as potential cathodes for high-performance supercapacitors. This current synthesis method is simple and can be extended to the preparation of other transition metal sulfide (TMS)-based electrode materials with exceptional electrochemical properties.
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BACKGROUND: Despite rapid advances in genomic-resolved metagenomics and remarkable explosion of metagenome-assembled genomes (MAGs), the function of uncultivated anaerobic lineages and their interactions in carbon mineralization remain largely uncertain, which has profound implications in biotechnology and biogeochemistry. RESULTS: In this study, we combined long-read sequencing and metatranscriptomics-guided metabolic reconstruction to provide a genome-wide perspective of carbon mineralization flow from polymers to methane in an anaerobic bioreactor. Our results showed that incorporating long reads resulted in a substantial improvement in the quality of metagenomic assemblies, enabling the effective recovery of 132 high-quality genomes meeting stringent criteria of minimum information about a metagenome-assembled genome (MIMAG). In addition, hybrid assembly obtained 51% more prokaryotic genes in comparison to the short-read-only assembly. Metatranscriptomics-guided metabolic reconstruction unveiled the remarkable metabolic flexibility of several novel Bacteroidales-affiliated bacteria and populations from Mesotoga sp. in scavenging amino acids and sugars. In addition to recovering two circular genomes of previously known but fragmented syntrophic bacteria, two newly identified bacteria within Syntrophales were found to be highly engaged in fatty acid oxidation through syntrophic relationships with dominant methanogens Methanoregulaceae bin.74 and Methanothrix sp. bin.206. The activity of bin.206 preferring acetate as substrate exceeded that of bin.74 with increasing loading, reinforcing the substrate determinantal role. CONCLUSION: Overall, our study uncovered some key active anaerobic lineages and their metabolic functions in this complex anaerobic ecosystem, offering a framework for understanding carbon transformations in anaerobic digestion. These findings advance the understanding of metabolic activities and trophic interactions between anaerobic guilds, providing foundational insights into carbon flux within both engineered and natural ecosystems. Video Abstract.
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Carbono , Metagenómica , Metano , Metano/metabolismo , Carbono/metabolismo , Metagenómica/métodos , Reactores Biológicos/microbiología , Metagenoma , Bacterias/genética , Bacterias/metabolismo , Bacterias/clasificación , Filogenia , Anaerobiosis , Transcriptoma , Genoma Bacteriano , Microbiota , Perfilación de la Expresión GénicaRESUMEN
OBJECTIVES: To evaluate the impact of previous cardiac surgery (PCS) on clinical outcomes after reoperative extended arch repair for acute type A aortic dissection. METHODS: This study included 37 acute type A aortic dissection patients with PCS (PCS group) and 992 without PCS (no-PCS group). Propensity score-matching yielded a subgroup of 36 pairs (1:1). In-hospital outcomes and mid-term survival were compared between the 2 groups. RESULTS: The PCS group was older (56.7 ± 14.2 vs 52.2 ± 12.6 years, P = 0.036) and underwent a longer cardiopulmonary bypass (median, 212 vs 183 min, P < 0.001) compared with the no-PCS group. Operative death occurred in 88 (8.6%) patients, exhibiting no significant difference between groups (13.5% vs 8.4%, P = 0.237). Major postoperative morbidity was observed in 431 (41.9%) patients, also showing no difference between groups (45.9% vs 41.7%, P = 0.615). Moreover, the multivariable logistic regression analysis revealed that PCS was not significantly associated with operative mortality (adjusted odds ratio 2.58, 95% confidence interval 0.91-7.29, P = 0.075) or major morbidity (adjusted odds ratio 1.92, 95% confidence interval 0.88-4.18, P = 0.101). The 3-year cumulative survival rates were 71.1% for the PCS group and 83.9% for the no-PCS group (log-rank P = 0.071). Additionally, Cox regression indicated that PCS was not significantly associated with midterm mortality (adjusted hazard ratio 1.40, 95% confidence interval 0.44-4.41, P = 0.566). After matching, no significant differences were found between groups in terms of operative mortality (P > 0.999), major morbidity (P > 0.999) and midterm survival (P = 0.564). CONCLUSIONS: No significant differences were found between acute type A aortic dissection patients with PCS and those without PCS regarding in-hospital outcomes and midterm survival after extended arch repair.
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Aneurisma de la Aorta Torácica , Disección Aórtica , Procedimientos Quirúrgicos Cardíacos , Reoperación , Humanos , Disección Aórtica/cirugía , Disección Aórtica/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Reoperación/estadística & datos numéricos , Estudios Retrospectivos , Aneurisma de la Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/mortalidad , Anciano , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Procedimientos Quirúrgicos Cardíacos/métodos , Complicaciones Posoperatorias/epidemiología , Aorta Torácica/cirugía , Resultado del Tratamiento , Enfermedad Aguda , Adulto , Implantación de Prótesis Vascular/métodos , Implantación de Prótesis Vascular/efectos adversos , Puntaje de PropensiónRESUMEN
INTRODUCTION: Patients with resolved hepatitis B virus infection undergoing rituximab are at risk of hepatitis B virus reactivation without antiviral prophylaxis. However, the risk in such patients treated with rituximab-based regimens for membranous nephropathy is not clear. We evaluated the risk of hepatitis B virus reactivation in membranous nephropathy patients with resolved infection undergoing rituximab-based regimens without antiviral prophylaxis. METHODS: Clinical data of 51 membranous nephropathy patients with resolved hepatitis B virus infection undergoing rituximab-based regimens without antiviral prophylaxis were retrospectively analyzed. Among these, 21 patients were followed for more than 1 year after rituximab discontinuation. The clinical data collected aimed to assess patients' responses and the risk of hepatitis B virus reactivation during and after rituximab treatment. RESULTS: 30/51 (58.8 %) patients reached complete or partial remission at 12 months. None of the patients experienced HBsAg seroreversion during rituximab treatment. Alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase and total bilirubin levels, as well as the numbers of patients who exceeded the upper limits of normal for alkaline phosphatase and prothrombin time, did not show any statistically significant difference during rituximab-based therapy. Neither did the anti-HBs level, the number of patients with protective anti-HBs titers exceeding 10 U/L, nor the levels of CD19+ B cells, CD4+ T cells, CD8+ T cells, and natural killer cells. Among the 21 patients followed for 12 (ranging from 12 to 19) months after rituximab discontinuation, no hepatitis B virus reactivation was observed. The mean anti-HBs level and the number of patients with anti-HBs titers over 10 U/L did not show any statistically significant difference during the extended follow-up of 33 patient-years. Neither did the CD4+ T cell, CD8+ T cell, nor the natural killer cell counts. One patient presented with an ALT level that exceeded the baseline value by three times and reached above 100 U/L, accompanied by elevations in AST, GGT, and ALP levels. Meanwhile, the anti-HBs titer was 816.09 U/L, and HBsAg was negative. CONCLUSION: The administration of rituximab-based regimens in membranous nephropathy patients with hepatitis B virus resolved infection leads to a low risk of hepatitis B virus reactivation without antiviral prophylaxis. Patient's immune status, drug combination, rituximab strategy should be fully evaluated when considering antiviral prophylaxis therapy.
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Glomerulonefritis Membranosa , Virus de la Hepatitis B , Hepatitis B , Rituximab , Activación Viral , Humanos , Rituximab/uso terapéutico , Rituximab/efectos adversos , Masculino , Femenino , Hepatitis B/inmunología , Hepatitis B/tratamiento farmacológico , Glomerulonefritis Membranosa/tratamiento farmacológico , Glomerulonefritis Membranosa/inmunología , Glomerulonefritis Membranosa/virología , Activación Viral/efectos de los fármacos , Persona de Mediana Edad , Virus de la Hepatitis B/fisiología , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/inmunología , Estudios Retrospectivos , Adulto , Anciano , Antivirales/uso terapéuticoRESUMEN
BACKGROUND: Understanding the interactions and dynamics of microbiotas within biological wastewater treatment systems is essential for ensuring their stability and long-term sustainability. In this study, we developed a systematic framework employing multi-omics and Hi-C sequencing to extensively investigate prokaryotic and phage communities within a hybrid biofilm and activated sludge system. RESULTS: We uncovered distinct distribution patterns, metabolic capabilities, and activities of functional prokaryotes through the analysis of 454 reconstructed prokaryotic genomes. Additionally, we reconstructed a phage catalog comprising 18,645 viral operational taxonomic units (vOTUs) with high length and contiguity using hybrid assembly, and a distinct distribution of phages was depicted between activated sludge (AS) and biofilm. Importantly, 1340 host-phage pairs were established using Hi-C and conventional in silico methods, unveiling the host-determined phage prevalence. The majority of predicted hosts were found to be involved in various crucial metabolic processes, highlighting the potential vital roles of phages in influencing substance metabolism within this system. Moreover, auxiliary metabolic genes (AMGs) related to various categories (e.g., carbohydrate degradation, sulfur metabolism, transporter) were predicted. Subsequent activity analysis emphasized their potential ability to mediate host metabolism during infection. We also profiled the temporal dynamics of phages and their associated hosts using 13-month time-series metagenomic data, further demonstrating their tight interactions. Notably, we observed lineage-specific infection patterns, such as potentially host abundance- or phage/host ratio-driven phage population changes. CONCLUSIONS: The insights gained from this research contribute to the growing body of knowledge surrounding interactions and dynamics of host-phage and pave the way for further exploration and potential applications in the field of microbial ecology. Video Abstract.
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Bacterias , Bacteriófagos , Aguas del Alcantarillado , Aguas Residuales , Bacteriófagos/genética , Bacteriófagos/clasificación , Bacteriófagos/fisiología , Bacteriófagos/aislamiento & purificación , Aguas del Alcantarillado/virología , Aguas del Alcantarillado/microbiología , Aguas Residuales/virología , Aguas Residuales/microbiología , Bacterias/virología , Bacterias/genética , Bacterias/clasificación , Biopelículas , Metagenómica , Purificación del Agua/métodos , MicrobiotaRESUMEN
Objective Upper-limb coordination is crucial for daily activities, especially among stroke survivors who may encounter obstacles during upper-limb rehabilitation. This study aimed to investigate the effects of thermal stimulation (TS) and transcutaneous electrical nerve stimulation (TENS) on sensory and motor function during recovery in acute stroke patients. Design This is a parallel study with a randomized controlled design. The experiment was conducted in the E-Da Hospital Rehabilitation Department, Kaohsiung, Taiwan. Intervention Thirty participants were in-patients with acute stroke at the E-Da Hospital. Participants were randomly assigned to three groups for a one-week intervention: exercise combined with TS, exercise combined with TENS, or conventional physical therapy with exercise alone. The Fugl-Meyer upper extremity scale, Brunnstrom stage, minimal current perception (MCP), and modified Ashworth scale were collected for the assessment. Results The outcomes demonstrated considerable improvement in MCP in all the groups after treatment. Specifically, the groups receiving TS and TENS showed significant improvements in the Brunnstrom stage, suggesting that both treatments improved distal motor recovery. Conclusion The results, following a one-week intervention period, suggested that both TS and TENS contributed to the improvement of motor and sensory function, with a significant impact on the Brunnstrom stage in the upper extremity, particularly in the distal region. The inclusion of TS or TENS in rehabilitation protocols improved distal motor function compared to baseline measures, suggesting these treatments as effective components in acute stroke rehabilitation.
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Advancements in machining technology demand higher speeds and precision, necessitating improved control systems in equipment like CNC machine tools. Due to lead errors, structural vibrations, and thermal deformation, commercial CNC controllers commonly use rotary encoders in the motor side to close the position loop, aiming to prevent insufficient stability and premature wear and damage of components. This paper introduces a multivariable iterative learning control (MILC) method tailored for flexible feed drive systems, focusing on enhancing dynamic positioning accuracy. The MILC employs error data from both the motor and table sides, enhancing precision by injecting compensation commands into both the reference trajectory and control command through a norm-optimization process. This method effectively mitigates conflicts between feedback control (FBC) and traditional iterative learning control (ILC) in flexible structures, achieving smaller tracking errors in the table side. The performance and efficacy of the MILC system are experimentally validated on an industrial biaxial CNC machine tool, demonstrating its potential for precision control in modern machining equipment.
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Direct ammonia oxidation (Dirammox) might be of great significance to advance the innovation of biological nitrogen removal process in wastewater treatment systems. However, it remains unknown whether Dirammox bacteria can be selectively enriched in activated sludge. In this study, a lab-scale bioreactor was established and operated for 2 months to treat synthetic wastewater with hydroxylamine as a selection pressure. Three Dirammox strains (Alcaligenes aquatilis SDU_AA1, Alcaligenes aquatilis SDU_AA2, and Alcaligenes sp. SDU_A2) were isolated from the activated sludge, and their capability to perform Dirammox process was confirmed. Although these three Dirammox bacteria were undetectable in the seed sludge (0%), their relative abundances rapidly increased after a month of operation, reaching 12.65%, 0.69%, and 0.69% for SDU_A2, SDU_AA1, and SDU_AA2, respectively. Among them, the most dominant Dirammox (SDU_A2) exhibited higher nitrogen removal rate (32.35%) than the other two strains (13.57% of SDU_AA1 and 14.52% of SDU_AA2). Comparative genomic analysis demonstrated that the most dominant Dirammox bacterium (SDU_A2) possesses fewer complete metabolic modules compared to the other two less abundant Alcaligenes strains. Our findings expanded the understanding of the application of Dirammox bacteria as key functional microorganisms in a novel biological nitrogen and carbon removal process if they could be well stabilized. KEY POINTS: ⢠Dirammox-dominated microbial community was enriched in activated sludge bioreactor. ⢠The addition of hydroxylamine played a role in Dirammox enrichment. ⢠Three Dirammox bacterial strains, including one novel species, were isolated.
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Alcaligenes , Reactores Biológicos , Nitrógeno , Oxidación-Reducción , Aguas Residuales , Aguas Residuales/microbiología , Aguas Residuales/química , Reactores Biológicos/microbiología , Nitrógeno/metabolismo , Alcaligenes/metabolismo , Alcaligenes/aislamiento & purificación , Alcaligenes/genética , Aguas del Alcantarillado/microbiología , Amoníaco/metabolismo , Purificación del Agua/métodos , Hidroxilamina/metabolismo , Filogenia , ARN Ribosómico 16S/genética , Bacterias/metabolismo , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , MicrobiotaRESUMEN
BACKGROUND: Studies have highlighted a possible crosstalk between the pathogeneses of COVID-19 and systemic lupus erythematosus (SLE); however, the interactive mechanisms remain unclear. We aimed to elucidate the impact of COVID-19 on SLE using clinical information and the underlying mechanisms of both diseases. METHODS: RNA-seq datasets were used to identify shared hub gene signatures between COVID-19 and SLE, while genome-wide association study datasets were used to delineate the interaction mechanisms of the key signaling pathways. Finally, single-cell RNA-seq datasets were used to determine the primary target cells expressing the shared hub genes and key signaling pathways. RESULTS: COVID-19 may affect patients with SLE through hematologic involvement and exacerbated inflammatory responses. We identified 14 shared hub genes between COVID-19 and SLE that were significantly associated with interferon (IFN)-I/II. We also screened and obtained four core transcription factors related to these hub genes, confirming the regulatory role of the IFN-I/II-mediated Janus kinase/signal transducers and activators of transcription (JAK-STAT) signaling pathway on these hub genes. Further, SLE and COVID-19 can interact via IFN-I/II and IFN-I/II receptors, promoting the levels of monokines, including interleukin (IL)-6/10, tumor necrosis factor-α, and IFN-γ, and elevating the incidence rate and risk of cytokine release syndrome. Therefore, in SLE and COVID-19, both hub genes and core TFs are enriched within monocytes/macrophages. CONCLUSIONS: The interaction between SLE and COVID-19 promotes the activation of the IFN-I/II-triggered JAK-STAT signaling pathway in monocytes/macrophages. These findings provide a new direction and rationale for diagnosing and treating patients with SLE-COVID-19 comorbidity.
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COVID-19 , Estudio de Asociación del Genoma Completo , Lupus Eritematoso Sistémico , SARS-CoV-2 , Transducción de Señal , Humanos , COVID-19/genética , Lupus Eritematoso Sistémico/genética , SARS-CoV-2/fisiología , Femenino , Quinasas Janus/metabolismo , Factores de Transcripción STAT/metabolismo , Factores de Transcripción STAT/genética , Masculino , Transcriptoma , Perfilación de la Expresión Génica , MultiómicaRESUMEN
The reconstruction of Cu catalysts during electrochemical reduction of CO2 is a widely known but poorly understood phenomenon. Herein, we examine the structural evolution of Cu nanocubes under CO2 reduction reaction and its relevant reaction conditions using identical location transmission electron microscopy, cyclic voltammetry, in situ X-ray absorption fine structure spectroscopy and ab initio molecular dynamics simulation. Our results suggest that Cu catalysts reconstruct via a hitherto unexplored yet critical pathway - alkali cation-induced cathodic corrosion, when the electrode potential is more negative than an onset value (e.g., -0.4 VRHE when using 0.1 M KHCO3). Having alkali cations in the electrolyte is critical for such a process. Consequently, Cu catalysts will inevitably undergo surface reconstructions during a typical process of CO2 reduction reaction, resulting in dynamic catalyst morphologies. While having these reconstructions does not necessarily preclude stable electrocatalytic reactions, they will indeed prohibit long-term selectivity and activity enhancement by controlling the morphology of Cu pre-catalysts. Alternatively, by operating Cu catalysts at less negative potentials in the CO electrochemical reduction, we show that Cu nanocubes can provide a much more stable selectivity advantage over spherical Cu nanoparticles.
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Pathogenic bacteria have consistently posed a formidable challenge to human health, creating the critical need for effective antibacterial solutions. In response, enzyme-metal-organic framework (MOF) composites have emerged as a promising class of antibacterial agents. This study focuses on the development of an enzyme-MOF composite based on HZIF-8, incorporating the advantages of simple synthesis, ZIF-8 antibacterial properties, lysozyme hydrolysis, and high biological safety. Through a one-pot method, core-shell nanoparticles (HZIF-8) were synthesized. This structure enables efficient immobilization of lysozyme and lactoferrin within the HZIF-8, resulting in the formation of the lysozyme-lactoferrin@HZIF-8 (LYZ-LF@HZIF-8) composite. Upon exposure to light irradiation, HZIF-8 itself possessed antibacterial properties. Lysozyme initiated the degradation of bacterial peptidoglycan and lactoferrin synergistically enhanced the antibacterial effect of lysozyme. All of the above ultimately contributed to comprehensive antibacterial activity. Antibacterial assessments demonstrated the efficacy of the LYZ-LF@HZIF-8 composite, effectively eradicating Staphylococcus aureus at a cell density of 1.5 × 106 CFU/mL with a low dosage of 200 µg/mL and completely inactivating Escherichia coli at 400 µg/mL with the same cell density. The enzyme-MOF composite exhibited significant and durable antibacterial efficacy, with no apparent cytotoxicity in vitro, thereby unveiling expansive prospects for applications in the medical and food industries.
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Antibacterianos , Escherichia coli , Lactoferrina , Estructuras Metalorgánicas , Pruebas de Sensibilidad Microbiana , Muramidasa , Staphylococcus aureus , Zeolitas , Muramidasa/farmacología , Muramidasa/química , Muramidasa/metabolismo , Lactoferrina/química , Lactoferrina/farmacología , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Estructuras Metalorgánicas/síntesis química , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Staphylococcus aureus/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Zeolitas/química , Zeolitas/farmacología , Imidazoles/química , Imidazoles/farmacología , Imidazoles/síntesis química , Porosidad , Propiedades de Superficie , Tamaño de la Partícula , Enzimas Inmovilizadas/química , Enzimas Inmovilizadas/farmacologíaRESUMEN
Digestive tract cancers are among the most common malignancies worldwide and have high incidence and mortality rates. Thus, the discovery of more effective diagnostic and therapeutic targets is urgently required. The development of technologies to accurately detect RNA modification has led to the identification of numerous RNA chemical modifications in humans (epitranscriptomics) that are involved in the occurrence and development of digestive tract cancers. RNA modifications can cooperatively regulate gene expression to facilitate normal physiological functions of the digestive system. However, the dysfunction of relevant RNA-modifying enzymes ("writers," "erasers," and "readers") can lead to the development of digestive tract cancers. Consequently, targeting dysregulated enzyme activity could represent a potent therapeutic strategy for the treatment of digestive tract cancers. In this review, we summarize the most widely studied roles and mechanisms of RNA modifications (m6A, m1A, m5C, m7G, A-to-I editing, pseudouridine [Ψ]) in relation to digestive tract cancers, highlight the crosstalk between RNA modifications, and discuss their roles in the interactions between the digestive system and microbiota during carcinogenesis. The clinical significance of novel therapeutic methods based on RNA-modifying enzymes is also discussed. This review will help guide future research into digestive tract cancers that are resistant to current therapeutics.
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Epigénesis Genética , Humanos , Animales , ARN/genética , ARN/metabolismo , Neoplasias Gastrointestinales/genética , Procesamiento Postranscripcional del ARN , Neoplasias del Sistema Digestivo/genética , Neoplasias del Sistema Digestivo/terapiaRESUMEN
Organic fluorescent materials with red/near-infrared (NIR) emission are highly promising for use in biotechnology due to their exceptional advantages. However, traditional red/NIR fluorophores often exhibit weak emission at high concentrations or in an aggregated state due to the aggregate-caused quenching effect, which severely limits their applicability in biological imaging. To address this challenge, we developed a series of cyanostyrene derivatives with aggregation-induced emission characteristics, including 2,3-Bis-(4-styryl-phenyl)-but-2-enedinitrile (DPB), 2,3-Bis-{4-[2-(4-methoxy- phenyl)-vinyl]-phenyl}-but-2-enedinitrile (DOB), 2,3-Bis-{4-[2-(4-diphenylamino- phenyl)-vinyl]-phenyl}-but-2-enedinitrile (DTB), and 2,3-Bis-[4-(2-{4-[phenyl- (4-triphenylvinyl-phenyl)-amino]-phenyl}-vinyl)- phenyl]-but-2-enedinitrile (DTTB). Notably, these compounds exhibited intense solid state fluorescence owing to AIE effect, especially DTTB shows NIR emission with high solid state quantum efficiency (712â nm, ΦF=14.2 %). Then we prepared DTTB@PS-PEG NPs nanoparticles by encapsulating DTTB with the amphiphilic polymer polystyrene-polyethylene glycol (PS-PEG). Importantly, DTTB@PS-PEG NPs exhibited highly efficient NIR luminescence (ΦF=28.7 %) and a large two-photon absorption cross-section (1900â GM) under 800â nm laser excitation. The bright two-photon fluorescence of DTTB@PS-PEG indicated that it can be a highly promising candidate for two-photon fluorescence probe. Therefore, this work provides valuable insights for the design of highly efficient and NIR-emitting two-photon fluorescent probes.
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OBJECTIVES: To observe the effect of electroacupuncture (EA) on behavior and hippocampal protein phosphorylation in rats with chronic fatigue syndrome (CFS), so as to explore its mechanisms underlying improvement of CFS. METHODS: Male SD rats were randomly divided into control, model and EA groups (n=12 rats in each group). The CFS model was established by chronic multifactor combined with stress stimulation (treadmill training + restraint stress + sleep disturbance + crowded environment). For rats of the EA group, EA (1 mA, frequency of 10 Hz) was applied to "Shenting" (GV24) (with an acupuncture needle penetrated from GV24 to "Baihui" ï¼»GV20ï¼½) and "Dazhui" (GV14) for 15 min, once daily for 28 days. After treatment, the body weight, food intake and water intake of rats in each group were observed. The fatigue degree of rats was evaluated by Semi-quantitative score observation table of the general condition of experimental rats.The open field test (OFT) was used to assess the rats'anxiety severity by detecting the total number of grid-crossing and the times of the central area entered in 5 min, and Morris water maze test was employed to assess the rats' learning-memory ability by detecting the escape latency in 1 min, and the times of the original platform quadrant crossing in 1 min. The hippocampaus was taken for phosphorylated Label-free quantitative proteomics analysis by using Maxquant technology based on full scan mode to calculate the integral of each peptide signal of liquid chromatography-mass spectrometry(LC-MS). The differentially-expressed proteins (>1.5 folds for up-regulation or <0.67 folds for down-regulation) were evaluated by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. RESULTS: Compared with the control group, the body weight, food intake, and the times of original-platform quadrant crossing of spatial exploring of Morris water maze test were significantly decreased (P<0.01, P<0.05) , and the score of general conditions, times of grid-crossing and center area-entering of OFT, and the escape latency of navigation task were apparently increased (P<0.01) in rats of the model group. After EA intervention, the decreased original-platform quadrant crossing, and the increased score of general conditions, times of grid-crossing and the escape latency of navigation task were all reversed (P<0.01, P<0.05). Outcomes of proteomics analysis indicated that compared with the model group, there were 297 differentially expressed peptide (48 up-regulated and 249 down-regulated) segments in the control group, and there were 245 differentially expressed peptide (185 up-regulated and 60 down-regulated) segments in the EA group, in which, 25 overlapping peptide segments were reversed after EA treatment, corresponding to 24 proteins, mainly involving cytoskeletal structure. GO function annotation analysis showed that the top three differentially expressed phosphorylated proteins involved in the effect of EA intervention were the actin filament polymerization, protein depolymerization and cytoskeletal tissue in the biological process, the actin binding, structural molecular activity and cytoskeletal protein binding in the molecular function, and the cytoskeleton, dendrites and dendritic trees in the cellular component, respectively. The KEGG pathway annotation analysis for differentially expressed phosphorylated proteins showed that theinsulin secretion, axon guidance, phosphatidylinositol signaling system and lysine biosynthesis, etc. were involved in the effect of EA intervention. CONCLUSIONS: EA of GV24-GV20 and GV14 can improve the general state, anxiety and learning-memory ability of CFS model rats, which may be related to its functions in regulating the hippocampal protein phosphorylation level, and repairing the structure and function of synapses in hippocampus.