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Alcoholic liver disease (ALD) is a chronic toxic liver injury caused by long-term heavy drinking. Due to the increasing incidence, ALD is becoming one of important medical tasks. Many studies have shown that the main mechanism of liver damage caused by large amounts of alcohol may be related to antioxidant stress. As an important antioxidant, cysteine (Cys) is involved in maintaining the normal redox balance and detoxifying metabolic function of the liver, which may be closely related to the pathogenesis of ALD. Therefore, it is necessary to develop a simple non-invasive method for rapid monitoring of Cys in liver. Thus, a near-infrared (NIR) fluorescent probe DCI-Ac-Cys which undergoes Cys triggered cascade reaction to form coumarin fluorophore is developed. Using the DCI-Ac-Cys, decreased Cys was observed in the liver of ALD mice. Importantly, different levels of Cys were monitored in the livers of ALD mice taking silybin and curcumin with the antioxidant effects, indicating the excellent therapeutic effect on ALD. This study provides the important references for the accurate diagnosis of ALD and the pharmacodynamic evaluation of silybin and curcumin in the treatment of ALD, and support new ideas for the pathogenesis of ALD.
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Cumarinas , Cisteína , Colorantes Fluorescentes , Hepatopatías Alcohólicas , Animales , Cisteína/análisis , Cisteína/metabolismo , Cumarinas/química , Colorantes Fluorescentes/química , Hepatopatías Alcohólicas/metabolismo , Hepatopatías Alcohólicas/patología , Masculino , Hígado/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Ratones , Ratones Endogámicos C57BL , Espectroscopía Infrarroja Corta/métodos , Curcumina/farmacología , Espectrometría de Fluorescencia , Silibina/farmacología , Silibina/químicaRESUMEN
The family Diatrypaceae is a less well-known group within the order Xylariales (Ascomycota). Initially, the focus on its metabolites was related to the pathogenicity of one of its members, Eutypa lata. To date, a total of 254 natural products have been identified from Diatrypaceae strains. These compounds include terpenoids, sterols, polyketones, phenols, and acetylene aromatic compounds, which have shown anticancer, cytotoxic, anti-inflammatory, antimicrobial, and antiviral activities. The complex and diverse structural types, along with the diverse bioactivities, highlight the potential of Diatrypaceae as a valuable source of bioactive natural products. In this review, a deep analysis of the biosynthesis of pimarane diterpenes and scoparasin-type cytochalasins is provided, coupled with a compilation of the biosynthetic pathways of aromatic acetylene compounds in filamentous fungi. This comprehensive review not only enhances our understanding of the natural product chemistry, biological activities, and biosynthesis of secondary metabolites from the Diatrypaceae family but also promotes the exploitation and development of important bioactive compounds and potential strains.
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Background: The tcdA gene codes for an important toxin produced by Clostridioides difficile (C. difficile), but there is currently no simple and cost-effective method of detecting it. This article establishes and validates a rapid and visual loop-mediated isothermal amplification (LAMP) assay for the detection of the tcdA gene. Methods: Three sets of primers were designed and optimized to amplify the tcdA gene in C. difficile using a LAMP assay. To evaluate the specificity of the LAMP assay, C. difficile VPI10463 was used as a positive control, while 26 pathogenic bacterial strains lacking the tcdA gene and distilled water were utilized as negative controls. For sensitivity analysis, the LAMP assay was compared to PCR using ten-fold serial dilutions of DNA from C. difficile VPI10463, ranging from 207 ng/µl to 0.000207 pg/µl. The tcdA gene of C.difficile was detected in 164 stool specimens using both LAMP and polymerase chain reaction (PCR). Positive and negative results were distinguished using real-time monitoring of turbidity and chromogenic reaction. Results: At a temperature of 66 °C, the target DNA was successfully amplified with a set of primers designated, and visualized within 60 min. Under the same conditions, the target DNA was not amplified with the tcdA12 primers for 26 pathogenic bacterial strains that do not carry the tcdA gene. The detection limit of LAMP was 20.700 pg/µl, which was 10 times more sensitive than that of conventional PCR. The detection rate of tcdA in 164 stool specimens using the LAMP method was 17% (28/164), significantly higher than the 10% (16/164) detection rate of the PCR method (X2 = 47, p < 0.01). Conclusion: LAMP method is an effective technique for the rapid and visual detection of the tcdA gene of C. difficile, and shows potential advantages over PCR in terms of speed, simplicity, and sensitivity. The tcdA-LAMP assay is particularly suitable for medical diagnostic environments with limited resources and is a promising diagnostic strategy for the screening and detection of C. difficile infection in populations at high risk.
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Toxinas Bacterianas , Clostridioides difficile , Infecciones por Clostridium , Enterotoxinas , Heces , Técnicas de Amplificación de Ácido Nucleico , Sensibilidad y Especificidad , Clostridioides difficile/genética , Clostridioides difficile/aislamiento & purificación , Técnicas de Amplificación de Ácido Nucleico/métodos , Humanos , Toxinas Bacterianas/genética , Infecciones por Clostridium/diagnóstico , Infecciones por Clostridium/microbiología , Heces/microbiología , Heces/química , Enterotoxinas/genética , Cartilla de ADN/genética , Técnicas de Diagnóstico Molecular/métodos , Reacción en Cadena de la Polimerasa/métodos , Adulto , Persona de Mediana EdadRESUMEN
Scheuchzeria palustris, the only species in the Scheuchzeriaceae family, plays a crucial role in methane production and transportation, influencing the global carbon cycle and maintaining ecosystem stability. However, it is now threatened by human activities and global warming. In this study, we generated new organelle genomes for S. palustris, with the plastome (pt) measuring 158,573 bp and the mitogenome (mt) measuring 420,724 bp. We predicted 296 RNA editing sites in mt protein-coding genes (PCGs) and 142 in pt-PCGs. Notably, abundant RNA editing sites in pt-PCGs likely originated from horizontal gene transfer between the plastome and mitogenome. Additionally, we identified positive selection signals in four mt-PCGs (atp4, ccmB, nad3, and sdh4) and one pt-PCG (rps7), which may contribute to the adaptation of S. palustris to low-temperature and high-altitude environments. Furthermore, we identified 35 mitochondrial plastid DNA (MTPT) segments totaling 58,479 bp, attributed to dispersed repeats near most MTPT. Phylogenetic trees reconstructed from mt- and pt-PCGs showed topologies consistent with the APG IV system. However, the conflicting position of S. palustris can be explained by significant differences in the substitution rates of its mt- and pt-PCGs (p < .001). In conclusion, our study provides vital genomic resources to support future conservation efforts and explores the adaptation mechanisms of S. palustris.
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BACKGROUND: The netrin-1/CD146 pathway regulates colorectal cancer (CRC) liver metastasis, angiogenesis, and vascular development. However, few investigations have yet examined the biological function of netrin-1/CD146 complex in CRC. In this work, we investigated the relationship between the netrin-1/CD146 axis and S100 proteins in sentinel lymph node, and revealed a possible new clue for vascular metastasis of CRC. METHODS: The expression levels of netrin-1 and CD146 proteins in CRC, as well as S100A8 and S100A9 proteins in the sentinel lymph nodes were determined by immunohistochemistry. Using GEPIA and UALCAN, we analyzed netrin-1 and CD146 gene expression in CRC, their association with CRC stage, and their expression levels and prognosis in CRC patients. RESULTS: The expression level of netrin-1 in N1a+1b (CRC lymphatic metastasis groups, exculded N1c) was positively increased with N0 (p = 0.012). The level of netrin-1 protein was positively correlated with CD146 protein (p < 0.05). The level of S100A9 protein was positively correlated with CD146 protein (r = 0.492, p = 0.007). Moreover, netrin-1 expression was obviously correlated with S100A9 expression in the N1 stage (r = 0.867, p = 0.000). CD146 level was correlated with S100A9 level in the N2 stage (r = 0.731, p = 0.039). CD146 mRNA expression was higher in normal colorectal tissues than in CRC (p < 0.05). Netrin-1 and CD146 expression were not significantly associated with the tumor stages and prognosis of patients with CRC (p > 0.05). CONCLUSIONS: The netrin-1/CD146 and netrin-1/S100A9 axis in CRC tissues might related with early stage of lymph node metastasis, thus providing potential novel channels for blocking lymphatic metastasis and guiding biomarker discovery in CRC patients.
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Antígeno CD146 , Calgranulina B , Neoplasias Colorrectales , Metástasis Linfática , Netrina-1 , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Calgranulina A/genética , Calgranulina A/metabolismo , Calgranulina B/genética , Calgranulina B/metabolismo , Antígeno CD146/genética , Antígeno CD146/metabolismo , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Ganglios Linfáticos/patología , Ganglios Linfáticos/metabolismo , Metástasis Linfática/genética , Metástasis Linfática/patología , Estadificación de Neoplasias , Netrina-1/metabolismo , Netrina-1/genética , PronósticoRESUMEN
By integrating the thermal characteristics from thermal-infrared remote sensing with the physiological and structural information of vegetation revealed by multispectral remote sensing, a more comprehensive assessment of the crop soil-moisture-status response can be achieved. In this study, multispectral and thermal-infrared remote-sensing data, along with soil-moisture-content (SMC) samples (0~20 cm, 20~40 cm, and 40~60 cm soil layers), were collected during the flowering stage of soybean. Data sources included vegetation indices, texture features, texture indices, and thermal-infrared vegetation indices. Spectral parameters with a significant correlation level (p < 0.01) were selected and input into the model as single- and fuse-input variables. Three machine learning methods, eXtreme Gradient Boosting (XGBoost), Random Forest (RF), and Genetic Algorithm-optimized Backpropagation Neural Network (GA-BP), were utilized to construct prediction models for soybean SMC based on the fusion of UAV multispectral and thermal-infrared remote-sensing information. The results indicated that among the single-input variables, the vegetation indices (VIs) derived from multispectral sensors had the optimal accuracy for monitoring SMC in different soil layers under soybean cultivation. The prediction accuracy was the lowest when using single-texture information, while the combination of texture feature values into new texture indices significantly improved the performance of estimating SMC. The fusion of vegetation indices (VIs), texture indices (TIs), and thermal-infrared vegetation indices (TVIs) provided a better prediction of soybean SMC. The optimal prediction model for SMC in different soil layers under soybean cultivation was constructed based on the input combination of VIs + TIs + TVIs, and XGBoost was identified as the preferred method for soybean SMC monitoring and modeling, with its R2 = 0.780, RMSE = 0.437%, and MRE = 1.667% in predicting 0~20 cm SMC. In summary, the fusion of UAV multispectral and thermal-infrared remote-sensing information has good application value in predicting SMC in different soil layers under soybean cultivation. This study can provide technical support for precise management of soybean soil moisture status using the UAV platform.
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Enantioenriched monofluoroalkenes are important structural motifs in life science and functional materials. To date, only limited strategies were reported for the synthesis of monofluoroalkenes with stereogenic carbon centers; the axially chiral counterpart is still highly desirable. Herein, we report Ni-catalyzed defluorinative cross-electrophile coupling of gem-difluoroalkenes with biaryl electrophiles for the synthesis of axially chiral monofluoroalkenes. The resulting axially chiral monofluoroalkenes are formed with excellent regio- and stereoselectivities. Synthetic transformation of these axially enantioenriched monofluoroalkenes was also demonstrated.
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Coherent optics has profoundly impacted diverse applications ranging from communications, LiDAR to quantum computations. However, developing coherent systems in integrated photonics comes at great expense in hardware integration and energy efficiency. Here we demonstrate a high-coherence parallelization strategy for advanced integrated coherent systems at minimal cost. By using a self-injection locked microcomb to injection lock distributed feedback lasers, we achieve a record high on-chip gain of 60 dB with no degradation in coherence. This strategy enables highly coherent channels with linewidths down to 10 Hz and power over 20 dBm. The overall electrical-to-optical efficiency reaches 19%, comparable to that of advanced semiconductor lasers. This method supports a silicon photonic communication link with an unprecedented data rate beyond 60 Tbit/s and reduces phase-related DSP consumption by 99.99999% compared to traditional III-V laser pump schemes. This work paves the way for realizing scalable, high-performance coherent integrated photonic systems, potentially benefiting numerous applications.
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Treatment with a magnetic induced electric field (MIEF) under acidic conditions has proven to be an effective method for modifying pectin, enhancing its functional attributes. In this study, the effects of varying excitation voltages of MIEF under acidic conditions on the physicochemical, structural, and functional properties of citrus pectin (CP) were explored. The results demonstrated that compared to CP without MIEF treatment, MIEF-treated CP exhibited enhanced thermal stability, rheological behavior, emulsifying and gel-forming abilities, and antioxidant capacity. These improvements were attributed to higher degrees of esterification, reduced molecular weights, and increased levels of galacturonic acid and homogalacturonan in the structural backbone of the treated CP. Additionally, MIEF treatment under acidic conditions altered the surface morphology and crystalline structure of CP. Therefore, our findings suggest that applying moderate excitation voltages (150-200 V) during MIEF treatment can enhance the functional properties of CP, leading to the production of high-quality modified pectin.
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Triple negative breast cancer (TNBC) is a particularly lethal breast cancer (BC) subtype driven by cancer stem cells (CSCs) and an immunosuppressive microenvironment. Our study reveals that nucleus accumbens associated protein 1 (NAC1), a member of the BTB/POZ gene family, plays a crucial role in TNBC by maintaining tumor stemness and influencing myeloid-derived suppressor cells (MDSCs). High NAC1 expression correlates with worse TNBC prognosis. NAC1 knockdown reduced CSC markers and tumor cell proliferation, migration, and invasion. Additionally, NAC1 affects oncogenic pathways such as the CD44-JAK1-STAT3 axis and immunosuppressive signals (TGFß, IL-6). Intriguingly, the impact of NAC1 on tumor growth varies with the host immune status, showing diminished tumorigenicity in natural killer (NK) cell-competent mice but increased tumorigenicity in NK cell-deficient ones. This highlights the important role of the host immune system in TNBC progression. In addition, high NAC1 level in MDSCs also supports TNBC stemness. Together, this study implies NAC1 as a promising therapeutic target able to simultaneously eradicate CSCs and mitigate immune evasion.
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Proliferación Celular , Células Supresoras de Origen Mieloide , Células Madre Neoplásicas , Neoplasias de la Mama Triple Negativas , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/genética , Humanos , Animales , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Femenino , Ratones , Células Supresoras de Origen Mieloide/metabolismo , Proteínas Represoras/metabolismo , Proteínas Represoras/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Microambiente Tumoral , Pronóstico , Movimiento Celular , Células Asesinas Naturales/metabolismo , Células Asesinas Naturales/inmunología , Proteínas de NeoplasiasRESUMEN
Long nanowires offer an increased surface area for biomolecule immobilization, facilitating enhanced binding capacity and sensitivity in the detection of target analytes. However, robust long-nanowire fabrication remains a significant challenge. In this paper, we developed a novel construction of a micro chemical pen (MCP), called a clean-assisted micro chemical pen (CAMCP), for robust long-nanowire fabrication. CAMCP, based on localized hydrodynamic flow confinement, was conducted by incorporating a clean phase to effectively dissolve aggregated silver particles in the aspiration channel's shell, thereby enhancing the MCP's longevity by 60.84%, allowing for an 840 µm extension in nanowire patterning capability. A 4600-aspect ratio (length:1200 µm, width: 260 nm) nanowire was fabricated by CAMCP and utilized as a nanowire sensor, showing a 39.7% increase in IgA detection sensitivity compared to a 3000-aspect ratio sensor. Furthermore, the longer nanowire sensor exhibited enhanced signal responses, a higher signal-to-noise ratio, and a lower limit of detection (LOD). The preponderant bioassay performances of the longer nanowire sensor in bioassays, facilitated by CAMCP, open up its possibilities for chemical-synthesis nanowires (NWs) in ultrasensitive biodetection.
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Nanocables , Nanocables/química , Bioensayo , Límite de Detección , Plata/química , Técnicas BiosensiblesRESUMEN
Seawater batteries are attracting continuous attention because seawater as an electrolyte is inexhaustible, eco-friendly, and free of charge. However, the rechargeable seawater batteries developed nowadays show poor reversibility and short cycle life, due to the very limited electrode materials and complicated yet inappropriate working mechanism. Here, we propose a rechargeable seawater battery that works through a rocking-chair mechanism encountered in commercial lithium ion batteries, enabled by intercalation-type inorganic electrode materials of open-framework-type cathode and Na-ion conducting membrane-type anode. The rechargeable seawater battery achieves a high specific energy of 80.0 Wh/kg at 1,226.9 W/kg and a high specific power of 7,495.0 W/kg at 23.7 Wh/kg. Additionally, it exhibits excellent cycling stability, retaining 66.3% of its capacity over 1,000 cycles. This work represents a promising avenue for developing sustainable aqueous batteries with low costs.
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Eighteen nitrogen-containing compounds (1-18) were isolated from cultures of the lichen-associated Streptomyces flavidovirens collected from the Qinghai-Tibet Plateau, including seven phenazine derivatives with three new ones, named subphenazines A-C (2-4), two new furan pyrrolidones (8-9), and nine known alkaloids. The structures were elucidated by spectroscopic data analysis, and absolute configurations were determined by single-crystal X-ray diffraction and ECD calculations. The phenazine-type derivatives, in particular compound 3, exhibited significantly better antineuroinflammatory activity than other isolated compounds (8-18). Compound 3 inhibited the release of proinflammatory cytokines including IL-6, TNF-α, and PGE2, and the nuclear translocation of NF-κB; it also reduced the oxidative stress and activated the Nrf2 signaling pathway in LPS-induced BV2 microglia cells. In vivo anti-inflammatory activity in zebrafish indicated that 3 inhibited LPS-stimulated ROS generation. These findings suggested that compound 3 might be a potent antineuroinflammatory agent through the regulation of the NF-κB/Nrf2 signaling pathways.
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Antiinflamatorios , Líquenes , FN-kappa B , Fenazinas , Streptomyces , Pez Cebra , Animales , Streptomyces/química , Líquenes/química , Antiinflamatorios/farmacología , Antiinflamatorios/química , Fenazinas/farmacología , Fenazinas/química , Estructura Molecular , FN-kappa B/metabolismo , Ratones , Factor 2 Relacionado con NF-E2/metabolismo , Transducción de Señal/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Microglía/efectos de los fármacos , Lipopolisacáridos/farmacología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND: Anemia is a common long-term metabolic sequela caused by anatomical changes after major gastrointestinal surgery, such as bariatric surgery and gastrectomy. Pancreaticoduodenectomy (PD) involves resection of the duodenum and enteral bypass, which may contribute to malabsorption and nutrient deficiency. Hence, PD may cause anemia. METHODS: This study included 322 patients who presented with PD during the 5-year follow-up from 2006 to 2017. The Kaplan-Meier method and the Cox regression model were used to investigate the association between risk factors and anemia. RESULTS: Approximately 44.4% of patients developed post-PD anemia during the 5-year post-PD follow-up. Further, 30 (9.3%) patients were treated with oral iron supplementation for anemia with associated symptoms. In the Cox multivariate model, a higher Charlson Comorbidity Index (CCI) score and pancreatic ductal adenocarcinoma were significantly associated with the development of post-PD anemia. CONCLUSION: Post-PD anemia is a common sequela among long-term survivors. A higher CCI and pancreatic ductal adenocarcinoma diagnosis were considered as independent risk factors for post-PD anemia. Therefore, regular monitoring of hematological profiles and appropriate management of post-PD anemia are required during follow-up.
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Pyrrolocarbazole skeletons are well known to possess a variety of biological activities that might be therapeutically useful in the treatment of cancers. Herein, an acid-catalyzed stereoselective hydroarylation/Diels-Alder cycloaddition/aromatization of ynamide-indoles is described. We newly designed and synthesized a variety of piperazine-fused pyrrolocarbazole derivatives that could be further applied to the synthesis of potent Wee1 inhibitors.
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We here show that the typical poison of thiols, if below a certain level, promotes rather than suppresses the catalytic activity of gold nanoclusters (AuNCs). A few thiol groups functionalized hyperbranched polyethylenimine (PEI, Mn = 2000 Da) patched on a mesoporous polymeric bead aid the direct synthesis of AuNCs. The nucleation efficiency of AuNC is 93-fold favored at a level of 2 thiols per PEI (0.04 equiv of the amino units) than that by neat PEI, and AuNCs (1.3 nm) are obtained up to a gold load of 6.3% on the support. Unexpectedly, the catalytic activity of AuNCs is favored by the thiol up to 2 thiols per PEI, as evaluated from the surface-normalized rate constant of the model reaction of 4-nitrophenol-reduction. The catalytic promotion by thiols probably stems from optimized electron density on AuNC. If the residual NH groups of PEI were further fully treated with glycidyltrimethylammonium chloride, the catalytic activity is again enhanced, where the accelerated mass transfer is responsible for the promotion. Overall, the catalytic activity reaches an unprecedented value (metal-normalized rate constant kc = 29.4 L mmol-1 s-1 and turnover frequency = 1623 h-1, as evaluated with the model reaction of 4-nitrophenol reduction) ever reported for supported AuNCs. Our results suggest that orthogonal ligand optimization is an effective manner of triggering the release of the catalytic potential of AuNCs, among which thiol is unique.