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BACKGROUND: Cancer-associated fibroblasts (CAFs) play a crucial role in the progression of colorectal cancer (CRC). However, the impact of CAF subpopulation trajectory differentiation on CRC remains unclear. METHODS: In this study, we first explored the trajectory differences of CAFs subpopulations using bulk and integrated single-cell sequencing data, and then performed consensus clustering of CRC samples based on the trajectory differential genes of CAFs subpopulations. Subsequently, we analyzed the heterogeneity of CRC subtypes using bioinformatics. Finally, we constructed relevant prognostic signature using machine learning and validated them using spatial transcriptomic data. RESULTS: Based on the differential genes of CAFs subpopulation trajectory differentiation, we identified two CRC subtypes (C1 and C2) in this study. Compared to C1, C2 exhibited worse prognosis, higher immune evasion microenvironment and high CAF characteristics. C1 was primarily associated with metabolism, while C2 was primarily associated with cell metastasis and immune regulation. By combining 101 combinations of 10 machine learning algorithms, we developed a High-CAF risk signatures (HCAFRS) based on the C2 characteristic gene. HCAFRS was an independent prognostic factor for CRC and, when combined with clinical parameters, significantly predicted the overall survival of CRC patients. HCAFRS was closely associated with epithelial-mesenchymal transition, angiogenesis, and hypoxia. Furthermore, the risk score of HCAFRS was mainly derived from CAFs and was validated in the spatial transcriptomic data. CONCLUSION: In conclusion, HCAFRS has the potential to serve as a promising prognostic indicator for CRC, improving the quality of life for CRC patients.
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Fibroblastos Asociados al Cáncer , Neoplasias Colorrectales , Microambiente Tumoral , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Humanos , Fibroblastos Asociados al Cáncer/patología , Fibroblastos Asociados al Cáncer/metabolismo , Pronóstico , Microambiente Tumoral/genética , Análisis por Conglomerados , Aprendizaje Automático , Biomarcadores de Tumor/genética , Transcriptoma , Regulación Neoplásica de la Expresión Génica , Perfilación de la Expresión Génica/métodos , Femenino , MasculinoRESUMEN
For practical engineering structures, fatigue is one of the main factors affecting their safety and durability. Under long-term service conditions, the minor damage will be affected by fatigue loading and expand to macroscopic cracks, affecting the structure's service performance. Based on the sensitivity of Lamb waves to minor and initial damage, a damage monitoring method for fatigue crack propagation is proposed. By carrying out fatigue crack propagation tests under constant amplitude loading, the Paris equation of 316L steel and damage signals at different crack growth stages were obtained. Combined with damage monitoring tests and finite element analysis, the relationship between the phase damage index (PDI), amplitude damage index (ADI), signal correlation coefficient, and fatigue crack propagation length was studied. Compared with PDI and ADI, the signal correlation coefficient is more sensitive to crack initiation, which can be selected as the damage monitoring index in the initial stage of crack growth. With the increase of fatigue crack propagation length, the peak time of the direct wave signal gradually moves backward, which shows an obvious phase change. In the whole fatigue crack growth stage, PDI and crack length show a monotonically changing trend. By using the stress intensity factor as the conversion parameter, a prediction model of the fatigue crack propagation rate based on PDI was established. Compared to the fatigue crack propagation rate measured by experiments, the relative error of the predicted results is 10%, which verifies the accuracy of the proposed damage monitoring method.
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Multi-needle electrospinning is an efficient method for producing nanofiber membranes. However, fluctuations in the fluid flow rate during the process affect membrane quality and cause instability, an issue that remains unresolved. To address this, a multi-stage flow runner spinneret needs to be developed for large-scale nanofiber membrane production. This paper uses COMSOL finite element software to simulate polymer flow in the spinneret runner. From this, the velocity field distribution and velocity instability coefficient were obtained, providing theoretical guidance for optimal spinneret design. In addition, response surface analysis (RSM) was used to experimentally explore the process parameters, and then residual probability plots were used for reliability verification to evaluate the effect of each process parameter on fiber diameter. These process parameters can guide the controlled production of nanofibers during multi-needle electrospinning.
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Euglena gracilis (E. gracilis), pivotal in the study of photosynthesis, endosymbiosis, and chloroplast development, is also an industrial microalga for paramylon production. Despite its importance, E. gracilis genome exploration faces challenges due to its intricate nature. In this study, we achieved a chromosome-level de novo assembly (2.37 Gb) using Illumina, PacBio, Bionano, and Hi-C data. The assembly exhibited a contig N50 of 619 Kb and scaffold N50 of 1.12 Mb, indicating superior continuity. Approximately 99.83% of the genome was anchored to 46 chromosomes, revealing structural insights. Repetitive elements constituted 58.84% of the sequences. Functional annotations were assigned to 39,362 proteins, enhancing interpretative power. BUSCO analysis confirmed assembly completeness at 80.39%. This first high-quality E. gracilis genome offers insights for genetics and genomics studies, overcoming previous limitations. The impact extends to academic and industrial research, providing a foundational resource.
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Euglena gracilis , Euglena gracilis/genética , Cromosomas , Microalgas/genética , Anotación de Secuencia Molecular , GlucanosRESUMEN
Tranexamic acid (TXA) is widely used among young women because of its ability to whiten skin and treat menorrhagia. Nevertheless, its potential effects on oocyte maturation and quality have not yet been clearly clarified. Melatonin (MT) is an endogenous hormone released by the pineal gland and believed to protect cells from oxidative stress injury. In the present study, we used in vitro maturation model to investigate the toxicity of TXA and the protective role of MT in mouse oocyte. Compared with the control group, TXA-exposed group had significantly lower nuclear maturation (57.72% vs. 94.08%, P < 0.001) and early embryo cleavage rates (38.18% vs. 87.66%, P < 0.001). Further study showed that spindle organization (52.56% vs. 18.77%, P < 0.01) and chromosome alignment (33.23% vs. 16.66%, P < 0.01) were also disrupted after TXA treatment. Mechanistically, we have demonstrated that TXA induced early apoptosis of oocytes (P < 0.001) by raising the level of ROS (P < 0.001), which was consistent with an increase in mitochondrial damage (P < 0.01). Fortunately, all these effects except the spindle defect were successfully rescued by an appropriate level of MT. Collectively, our findings indicate that MT could partially reverse TXA-induced oocyte quality deterioration in mouse by effectively improving mitochondrial function and reducing oxidative stress-mediated apoptosis.
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Although studies have revealed the significant impact of dietary fiber on growth performance and nutrient digestibility, the specific characteristics of the intestinal microbiota and gene regulation in pigs capable of digesting high-fiber diets remained unclear. To investigate the traits associated with roughage tolerance in the Chinese indigenous pig breed, we conducted comparative analysis of growth performance, apparent fiber digestibility, intestinal microbiota, SCFA concentrations and intestinal transcriptome in Tunchang pigs, feeding them diets with different wheat bran levels. The results indicated that the growth performance of Tunchang pigs was not significantly impacted, and the apparent total tract digestibility of crude fiber was significantly improved with increasing dietary fiber content. High-fiber diets altered the diversity of intestinal microbiota, and increased the relative abundance of Prevotella, CF231, as well as the concentrations of isobutyrate, valerate and isovalerate. The LDA analysis identified potential microbial biomarkers that could be associated with roughage tolerance, such as Prevotella stercorea, and Eubacterium biforme. In addition, appropriate high-fiber diets containing 4.34% crude fiber upregulated the mRNA expressions of PYY, AQP8, and SLC5A8, while downregulating the mRNA expressions of CKM and CNN1.This indicated that appropriate high-fiber diets may inhibit intestine motility and increase the absorption of water and SCFAs.
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Simultaneous CO2 sequestration and nitrate removal can be achieved by co-cultivation of Chlorella vulgaris with Pseudomonas sp. However, a comprehensive understanding of the synergistic mechanism between C. vulgaris and Pseudomonas sp. remains unknown. In this study, transcriptomics and metabolomics analysis were employed to elucidate the synergistic mechanism of C. vulgaris and Pseudomonas sp. Transcriptomic and metabolomic analyses identified 3664 differentially expressed genes and 314 metabolites. Transcriptome analysis revealed that co-culture with Pseudomonas sp. promoted the photosynthesis of C. vulgaris by promoting the synthesis of photosynthetic pigments and photosynthesis-antenna proteins. Furthermore, it stimulated pathways associated with energy metabolism from carbon sources, such as the Calvin cycle, glycolytic pathway, and TCA cycle. Additionally, Pseudomonas sp. reduced nitrate levels in the co-culture system by denitrification, and microalgae regulated nitrate uptake by down-regulating the transcript levels of nitrate transporter genes. Metabolomic analysis indicated that nutrient exchange was conducted between algae and bacteria, and amino acids, phytohormones, and organic heterocyclic compounds secreted by the bacteria promoted the growth metabolism of microalgae. After supplementation with differential metabolites, the carbon fixation rate and nitrate removal rate of the co-culture system reached 0.549 g L-1 d-1 and 135.4 mg L-1 d-1, which were increased by 20% and 8%, respectively. This study provides a theoretical insight into microalgae-bacteria interaction and its practical application, as well as a novel perspective on flue gas treatment management.
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In this study, the effects of soil conditioners on the growth and development of melons and the rhizosphere soil environment were explored. The optimal amount of added soil conditioner was screened to solve the practical production problems of high-quality and high-yield thin-skinned melon. The melon variety "Da Shetou" was used as the material. Under the conditions of conventional fertilization and cultivation technology management, different soil conditioners were set up for potted melons. The effects of Pastoral soil (CK), 95% Pastoral soil + 5% volcanic ash soil conditioner (KT1), 85% Pastoral soil + 15% volcanic ash soil conditioner (KT2), 75% Pastoral soil + 25% volcanic ash soil conditioner (KT3), 65% Pastoral soil + 35% volcanic ash soil conditioner (KT4), and 55% Pastoral soil + 45% volcanic ash soil conditioner (KT5) on melon yield, quality, and rhizosphere soil characteristics were investigated. The soil microbial community was analyzed using Illumina MiSeq technology. Compared to CK, KT1, KT3, KT4, and KT5, the KT2 treatment could improve the single fruit yield of melon, increasing it by 4.35%, 2.48%, 2.31%, 5.92%, and 2.92%. Meanwhile, the highest contents of soluble protein, soluble solid, and soluble sugar in the KT2 treatment were 1.89 mg·100 g-1, 16.35%, and 46.44 mg·g-1, which were significantly higher than those in the control treatment. The contents of organic matter, total nitrogen, alkali-soluble nitrogen, nitrate nitrogen, ammonium nitrogen, available potassium, and available phosphorus in melon rhizosphere soil were the highest in the KT2 treatment. Through Alpha diversity analysis, it was found that the Chao1 index, Shannon index, and ACE index were significantly higher in the KT1 treatment than in the control, while, among all groups, the Simpson index and coverage were not significantly different. The dominant bacteria in the six treated samples were mainly Actinobacteriota, Proteobacteria, Cyanobacteria, Chloroflexi, Acidobacteria, Bacteroidetes, Myxomycota, Firmicutes, Gemmatimonadota, Verrucomicrobia, and Planctomycetes, which accounted for 96.59~97.63% of the relative abundance of all bacterial groups. Through redundancy analysis (RDA), it was found that the organic matter, electrical conductivity, available phosphorus, and nitrate nitrogen of melon rhizosphere soil were the dominant factors of bacterial community change at the dominant genus level. In summary, 15% ash soil conditioner applied on melon was the selected treatment to provide a theoretical reference for the application of soil conditioner in facility cultivation.
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Tributyltin chloride (TBTC) is a ubiquitous environmental pollutant with various adverse effects on human health. Exosomes are cell - derived signaling and substance transport vesicles. This investigation aimed to explore whether exosomes could impact the toxic effects caused by TBTC via their transport function. Cytotoxicity, DNA and chromosome damage caused by TBTC on MCF-7 cells were analyzed with CCK-8, flow cytometry, comet assay and micronucleus tests, respectively. Exosomal characterization and quantitative analysis were performed with ultracentrifugation, transmission electron microscope (TEM) and bicinchoninic acid (BCA) methods. TBTC content in exosomes was detected with Liquid Chromatography-Mass Spectrometry (LC-MS). The impacts of exosomal secretion on the toxic effects of TBTC were analyzed. Our data indicated that TBTC caused significant cytotoxicity, DNA and chromosome damage effects on MCF-7 cells, and a significantly increased exosomal secretion. Importantly, TBTC could be transported out of MCF-7 cells by exosomes. Further, when exosomal secretion was blocked with GW4869, the toxic effects of TBTC were significantly exacerbated. We concluded that TBTC promoted exosomal secretion, which in turn transported TBTC out of the source cells to alleviate its toxic effects. This investigation provided a novel insight into the role and mechanism of exosomal release under TBTC stress.
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Daño del ADN , Exosomas , Compuestos de Trialquiltina , Humanos , Exosomas/efectos de los fármacos , Exosomas/metabolismo , Compuestos de Trialquiltina/toxicidad , Células MCF-7 , Daño del ADN/efectos de los fármacos , Transporte Biológico/efectos de los fármacos , Contaminantes Ambientales/toxicidad , Supervivencia Celular/efectos de los fármacosRESUMEN
The mechanistic target of rapamycin (RAPA) complex 1 (mTORC1) - transcription factor EB (TFEB) pathway plays a crucial role in response to nutritional status, energy and environmental stress for maintaining cellular homeostasis. But there is few reports on its role in the toxic effects of arsenic exposure and the related mechanisms. Here, we show that the exposure of bronchial epithelial cells (BEAS-2B) to sodium arsenite promoted the activation of mTORC1 (p-mTORC1) and the inactivation of TFEB (p-TFEB), the number and activity of lysosomes decreased, the content of reduced glutathione (GSH) and superoxide dismutase (SOD) decreased, the content of malondialdehyde (MDA) increased, the DNA and chromosome damage elevated. Further, when mTORC1 was inhibited with RAPA, p-mTORC1 and p-TFEB down-regulated, GSH and SOD increased, MDA decreased, the DNA and chromosome damage reduced significantly, as compared with the control group. Our data revealed for the first time that mTORC1 - TFEB pathway was involved in sodium arsenite induced lysosomal alteration, oxidative stress and genetic damage in BEAS-2B cells, and it may be a potential intervention target for the toxic effects of arsenic.
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Arsenitos , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice , Daño del ADN , Lisosomas , Diana Mecanicista del Complejo 1 de la Rapamicina , Estrés Oxidativo , Compuestos de Sodio , Arsenitos/toxicidad , Compuestos de Sodio/toxicidad , Estrés Oxidativo/efectos de los fármacos , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Lisosomas/efectos de los fármacos , Lisosomas/metabolismo , Humanos , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Línea Celular , Daño del ADN/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Transducción de Señal/efectos de los fármacos , Bronquios/efectos de los fármacos , Bronquios/metabolismo , Bronquios/citología , Bronquios/patología , Glutatión/metabolismo , Superóxido Dismutasa/metabolismo , Complejos Multiproteicos/metabolismo , Malondialdehído/metabolismoRESUMEN
Lead is a widespread environmental pollutant with serious adverse effects on human health, but the mechanism underlying its toxicity remains elusive. This study aimed to investigate the role of miR-584-5p / Ykt6 axis in the toxic effect of lead on HK-2 cells and the related mechanism. Our data suggested that lead exposure caused significant cytotoxicity, DNA and chromosome damage to HK-2 cells. Mechanistically, lead exposure down-regulated miR-584-5p and up-regulated Ykt6 expression, consequently, autophagosomal number and autophagic flux increased, lysosomal number and activity decreased, exosomal secretion increased. Interestingly, when miR-584-5p level was enhanced with mimic, autophagosomal number and autophagic flux decreased, lysosomal number and activity increased, ultimately, exosomal secretion was down-regulated, which resulted in significant aggravated toxic effects of lead. Further, directly blocking exosomal secretion with inhibitor GW4869 also resulted in exacerbated toxic effects of lead. Herein, we conclude that miR-584-5p / Ykt6 - mediated autophagy - lysosome - exosome pathway may be a critical route affecting the toxic effects of lead on HK-2 cells. We provide a novel insight into the mechanism underlying the toxicity of lead on human cells.
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Autofagia , Exosomas , Plomo , Lisosomas , MicroARNs , Humanos , Autofagia/efectos de los fármacos , MicroARNs/genética , MicroARNs/metabolismo , Exosomas/efectos de los fármacos , Exosomas/metabolismo , Lisosomas/efectos de los fármacos , Línea Celular , Plomo/toxicidad , Contaminantes Ambientales/toxicidad , ATPasas de Translocación de Protón Vacuolares/genética , Daño del ADNRESUMEN
Importance: Infections due to multidrug-resistant organisms (MDROs) are associated with increased morbidity, mortality, length of hospitalization, and health care costs. Regional interventions may be advantageous in mitigating MDROs and associated infections. Objective: To evaluate whether implementation of a decolonization collaborative is associated with reduced regional MDRO prevalence, incident clinical cultures, infection-related hospitalizations, costs, and deaths. Design, Setting, and Participants: This quality improvement study was conducted from July 1, 2017, to July 31, 2019, across 35 health care facilities in Orange County, California. Exposures: Chlorhexidine bathing and nasal iodophor antisepsis for residents in long-term care and hospitalized patients in contact precautions (CP). Main Outcomes and Measures: Baseline and end of intervention MDRO point prevalence among participating facilities; incident MDRO (nonscreening) clinical cultures among participating and nonparticipating facilities; and infection-related hospitalizations and associated costs and deaths among residents in participating and nonparticipating nursing homes (NHs). Results: Thirty-five facilities (16 hospitals, 16 NHs, 3 long-term acute care hospitals [LTACHs]) adopted the intervention. Comparing decolonization with baseline periods among participating facilities, the mean (SD) MDRO prevalence decreased from 63.9% (12.2%) to 49.9% (11.3%) among NHs, from 80.0% (7.2%) to 53.3% (13.3%) among LTACHs (odds ratio [OR] for NHs and LTACHs, 0.48; 95% CI, 0.40-0.57), and from 64.1% (8.5%) to 55.4% (13.8%) (OR, 0.75; 95% CI, 0.60-0.93) among hospitalized patients in CP. When comparing decolonization with baseline among NHs, the mean (SD) monthly incident MDRO clinical cultures changed from 2.7 (1.9) to 1.7 (1.1) among participating NHs, from 1.7 (1.4) to 1.5 (1.1) among nonparticipating NHs (group × period interaction reduction, 30.4%; 95% CI, 16.4%-42.1%), from 25.5 (18.6) to 25.0 (15.9) among participating hospitals, from 12.5 (10.1) to 14.3 (10.2) among nonparticipating hospitals (group × period interaction reduction, 12.9%; 95% CI, 3.3%-21.5%), and from 14.8 (8.6) to 8.2 (6.1) among LTACHs (all facilities participating; 22.5% reduction; 95% CI, 4.4%-37.1%). For NHs, the rate of infection-related hospitalizations per 1000 resident-days changed from 2.31 during baseline to 1.94 during intervention among participating NHs, and from 1.90 to 2.03 among nonparticipating NHs (group × period interaction reduction, 26.7%; 95% CI, 19.0%-34.5%). Associated hospitalization costs per 1000 resident-days changed from $64â¯651 to $55â¯149 among participating NHs and from $55â¯151 to $59â¯327 among nonparticipating NHs (group × period interaction reduction, 26.8%; 95% CI, 26.7%-26.9%). Associated hospitalization deaths per 1000 resident-days changed from 0.29 to 0.25 among participating NHs and from 0.23 to 0.24 among nonparticipating NHs (group × period interaction reduction, 23.7%; 95% CI, 4.5%-43.0%). Conclusions and Relevance: A regional collaborative involving universal decolonization in long-term care facilities and targeted decolonization among hospital patients in CP was associated with lower MDRO carriage, infections, hospitalizations, costs, and deaths.
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Antiinfecciosos Locales , Infecciones Bacterianas , Infección Hospitalaria , Farmacorresistencia Bacteriana Múltiple , Instituciones de Salud , Control de Infecciones , Anciano , Humanos , Administración Intranasal , Antiinfecciosos Locales/administración & dosificación , Antiinfecciosos Locales/uso terapéutico , Infecciones Bacterianas/economía , Infecciones Bacterianas/microbiología , Infecciones Bacterianas/mortalidad , Infecciones Bacterianas/prevención & control , Baños/métodos , California/epidemiología , Clorhexidina/administración & dosificación , Clorhexidina/uso terapéutico , Infección Hospitalaria/economía , Infección Hospitalaria/microbiología , Infección Hospitalaria/mortalidad , Infección Hospitalaria/prevención & control , Instituciones de Salud/economía , Instituciones de Salud/normas , Instituciones de Salud/estadística & datos numéricos , Hospitalización/economía , Hospitalización/estadística & datos numéricos , Hospitales/normas , Hospitales/estadística & datos numéricos , Control de Infecciones/métodos , Yodóforos/administración & dosificación , Yodóforos/uso terapéutico , Casas de Salud/economía , Casas de Salud/normas , Casas de Salud/estadística & datos numéricos , Transferencia de Pacientes , Mejoramiento de la Calidad/economía , Mejoramiento de la Calidad/estadística & datos numéricos , Cuidados de la Piel/métodos , Precauciones UniversalesRESUMEN
Flexible and stretchable organic solar cells (OSCs) show great promise in wearable and stretchable electronic applications. However, current high-performance OSCs consisting of polymer donors (PDs) and small-molecule acceptors (SMAs) face significant challenges in achieving both high power conversion efficiency (PCE) and excellent stretch-ability. In this study, we synthesized a new polymerized-small-molecule acceptor (P-SMA) PY-SiO featuring siloxane-terminated side chains and compared its photovoltaic and mechanical performance to that of the reference PY-EH with ethylhexyl-terminated side chains. We found that the incorporation of siloxane-terminated side chains in PY-SiO enhanced the molecular aggregation and charge transport, leading to an optimized film morphology. The resultant of all-polymer solar cells (all-PSCs) based on PBDB-T/PY-SiO showed a higher PCE of 12.04% than the PY-EH-based one (10.85%). Furthermore, the siloxane-terminated side chains also increased the interchain distance and provided a larger free volume for chain rotation and reconfiguration, resulting in a higher film crack-onset strain (COS: 18.32% for PBDB-T/PY-SiO vs 11.15% for PBDB-T/PY-EH). Additionally, the PY-SiO-based stretchable all-PSCs exhibited an impressive PCE of 9.8% and retained >70% of its original PCE even under a substantial 20% strain, exceeding the performance of the PY-EH-based stretchable all-PSCs. Our result suggests the great potential of the siloxane-terminated side chain for achieving high-performance and stretchable OSCs.
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Dopamine (DA) is a key regulator of associative learning and memory in both vertebrates and invertebrates, and it is widely believed that DA plays a key role in aversive conditioning in invertebrates. However, the idea that DA is involved only in aversive conditioning has been challenged in recent studies on the fruit fly (Drosophila melanogaster), ants and crabs, suggesting diverse functions of DA modulation on associative plasticity. Here, we present the results of DA modulation in aversive olfactory conditioning with DEET punishment and appetitive olfactory conditioning with sucrose reward in the oriental fruit fly, Bactrocera dorsalis. Injection of DA receptor antagonist fluphenazine or chlorpromazine into these flies led to impaired aversive learning, but had no effect on the appetitive learning. DA receptor antagonists impaired both aversive and appetitive long-term memory retention. Interestingly, the impairment on appetitive memory was rescued not only by DA but also by octopamine (OA). Blocking the OA receptors also impaired the appetitive memory retention, but this impairment could only be rescued by OA, not by DA. Thus, we conclude that in B. dorsalis, OA and DA pathways mediate independently the appetitive and aversive learning, respectively. These two pathways, however, are organized in series in mediating appetitive memory retrieval with DA pathway being at upstream. Thus, OA and DA play dual roles in associative learning and memory retrieval, but their pathways are organized differently in these two cognitive processes - parallel organization for learning acquisition and serial organization for memory retrieval.
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Dopamina , Drosophila melanogaster , Tephritidae , Animales , Dopamina/metabolismo , Dopamina/farmacología , Drosophila melanogaster/metabolismo , Memoria , Antagonistas de Dopamina/farmacologíaRESUMEN
The accumulation of heterocyclic amines (HAs) and advanced glycation end products (AGEs) in thermally processed meats has been arising safety concerns. The effects of cooking conditions and seasoning addition on the formation of HAs and AGEs in Chinese traditional braised lamb were investigated by UPLC-MS/MS analysis. Soy sauce significantly increased the formation of HAs and AGEs, among which light soy sauce had the greatest promoting effect (69.45-15300.62 %). Conversely, spices inhibited HAs and AGEs formation, the inhibition rate of free HAs and AGEs reached 22.06-34.72 % when using 70 % ethanol extract. Hot blanching treatment and adding soy sauce and spices at a later stage could significantly suppress HAs and AGEs production. Flavonoids, including galangin, hesperidin, narirutin, etc., were identified as key effectors in spices. These findings help to promote awareness of the formation of HAs and AGEs in braised lamb and provide valuable insights for optimizing processing techniques to minimize their production.
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Compuestos Heterocíclicos , Espectrometría de Masas en Tándem , Animales , Ovinos , Cromatografía Liquida , Espectrometría de Masas en Tándem/métodos , Compuestos Heterocíclicos/análisis , Culinaria/métodos , Aminas/análisis , Productos Finales de Glicación Avanzada/análisisRESUMEN
The modification of starch digestibility can be achieved through the formation of complexes with polyphenols. We studied the combined impacts of ultrasound and high-pressure homogenization (UT-HPH) on the structure and in vitro digestibility of rice starch-chlorogenic acid complexes. The development of V-type complexes was supported by our findings, which also showed that synergistic UT-HPH therapy exhibited the highest absorbance value for the complexing index (0.882). Significant alterations in digestibility were also observed in the complexes, with the content of RDS decreasing from 49.27% to 27.06%, the content of slowly SDS increasing from 25.69% to 35.35%, and the percentage of RS increasing from 25.05% to 37.59%. Furthermore, a high positive correlation was found by applying the Pearson correlation coefficient in our research between RS, weight, PSD, and CI. This study presents a sustainable processing approach for utilizing chlorogenic acid in starch-rich food systems.
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Oryza , Almidón , Almidón/química , Ácido Clorogénico , Digestión , Hidroxibenzoatos , Oryza/químicaRESUMEN
A highly powerful nanosecond pulsed deep-red laser was demonstrated by intracavity second-harmonic generation of an actively Q-switched Nd:YLF dual-crystal-based KGW Raman laser in a critically phase-matched lithium triborate (LBO) crystal. The first-Stokes fields at 1461 and 1490â nm driven by the 1314â nm fundamental laser were firstly produced by accessing the Raman shifts of 768 and 901â cm-1 in the KGW crystal, respectively, and thereafter converted to the deep-red emission lines at 731 and 745â nm by finely tuning the phase-matching angle of the LBO crystal and carefully realigning the resonator. Integrating the benefits of the Nd:YLF dual-crystal configuration and the meticulously designed L-shaped resonator, this deep-red laser system delivered the maximum average output powers of 5.2 and 7.6â W with the optical power conversion efficiencies approaching 6.3% and 9.2% under the optimal pulse repetition frequency of 4â kHz, respectively. The pulse durations of 6.7 and 5.5â ns were acquired with the peak powers up to approximately 190 and 350â kW, respectively, and the resultant beam qualities were determined to be near-diffraction-limited with M2 ≈ 1.5.
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Multiple sclerosis (MS) is a leading cause of chronic neurological dysfunction in young to middle-aged adults, affecting approximately 2.5 million people worldwide. It is characterized by inflammation, multifocal demyelination, axonal loss, and white and gray matter gliosis. Autophagy is a highly conserved protein degradation pathway. Polymorphisms in autophagy-related genes have been implicated in a variety of autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, psoriasis and MS. However, the significance of autophagy in MS remains to be elucidated. This paper aims to explore the potential role of autophagy-related genes in MS diseases by using bioinformatics combined with machine learning methods. Finally, we obtained 9 autophagy genes with the highest correlation with MS, and further changes in these autophagy genes were verified in the experimental autoimmune encephalomyelitis (EAE) model and oligodendrocyte precursor cells (OPCs) engulfed myelin debris (MD). Combined with bioinformatic analysis and experimental data, Becn1 showed obvious expression abnormalities suggesting that this gene has vital functions in autophagy and MD engulfed by OPCs. This work will be of great significance for the further exploration of autophagy-related genes in demyelinating diseases.
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We demonstrate the first ten-watt-level eye-safe intracavity crystalline Raman laser, to the best of our knowledge. The efficient high-power eye-safe Raman laser is intracavity-pumped by an acousto-optically Q-switched 1314â nm two-crystal Nd:YLF laser. Benefiting from the unique bi-axial properties of KGW crystal, two sets of eye-safe dual-wavelength Raman lasers operating at 1461, 1645â nm and 1490, 1721nm are achieved by rotating the Raman crystal. Under the launched pump power of 84.9 W and the repetition rate of 4 kHz, the maximum first-Stokes output powers of 7.9 W at 1461â nm and 8.2 W at 1490â nm are acquired with the second-Stokes output powers of 1.4 W at 1645â nm and 1.5 W at 1721nm, respectively, leading to the eye-safe dual-wavelength Raman output powers of up to 9.3 and 9.7 W. Meanwhile, the pulse durations at the wavelengths of 1461, 1490, 1645, 1721nm are determined to be 4.8, 5.5, 4.3, and 3.6â ns, respectively, which give rise to the peak powers approaching about 410, 370, 80, 100â kW. These Stokes emissions are found to be near diffraction limited with M2 < 1.6 across the entire output power range.
RESUMEN
BACKGROUND AND AIMS: Metabolic dysfunction-associated steatohepatitis (MASH) fibrosis is a reversible stage of liver disease accompanied by inflammatory cell infiltration. Neutrophils extrude a meshwork of chromatin fibers to establish neutrophil extracellular traps (NETs), which play important roles in inflammatory response regulation. Our previous work demonstrated that NETs promote HCC in MASH. However, it is still unknown if NETs play a role in the molecular mechanisms of liver fibrosis. APPROACH AND RESULTS: Following 12 weeks of Western diet/carbon tetrachloride, MASH fibrosis was identified in C57BL/6 mice with increased NET formation. However, NET depletion using DNase I treatment or mice knocked out for peptidyl arginine deaminase type IV significantly attenuated the development of MASH fibrosis. NETs were demonstrated to induce HSCs activation, proliferation, and migration through augmented mitochondrial and aerobic glycolysis to provide additional bioenergetic and biosynthetic supplies. Metabolomic analysis revealed markedly an altered metabolic profile upon NET stimulation of HSCs that were dependent on arachidonic acid metabolism. Mechanistically, NET stimulation of toll-like receptor 3 induced cyclooxygenase-2 activation and prostaglandin E2 production with subsequent HSC activation and liver fibrosis. Inhibiting cyclooxygenase-2 with celecoxib reduced fibrosis in our MASH model. CONCLUSIONS: Our findings implicate NETs playing a critical role in the development of MASH hepatic fibrosis by inducing metabolic reprogramming of HSCs through the toll-like receptor 3/cyclooxygenase-2/cyclooxygenase-2 pathway. Therefore, NET inhibition may represent an attractive treatment target for MASH liver fibrosis.