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Since wearable technologies for telemedicine have emerged to tackle global health concerns, the demand for well-attested wearable healthcare devices with high user comfort also arises. Skin-wearables for health monitoring require mechanical flexibility and stretchability for not only high compatibility with the skin's dynamic nature but also a robust collection of fine health signals from within. Stretchable electrical interconnects, which determine the device's overall integrity, are one of the fundamental units being understated in wearable bioelectronics. In this review, a broad class of materials and engineering methodologies recently researched and developed are presented, and their respective attributes, limitations, and opportunities in designing stretchable interconnects for wearable bioelectronics are offered. Specifically, the electrical and mechanical characteristics of various materials (metals, polymers, carbons, and their composites) are highlighted, along with their compatibility with diverse geometric configurations. Detailed insights into fabrication techniques that are compatible with soft substrates are also provided. Importantly, successful examples of establishing reliable interfacial connections between soft and rigid elements using novel interconnects are reviewed. Lastly, some perspectives and prospects of remaining research challenges and potential pathways for practical utilization of interconnects in wearables are laid out.
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Infertility is a global health problem affecting millions of people of reproductive age worldwide, with approximately half caused by males. Chitosan oligosaccharide (COS) has strong antioxidant capacity, but its impact on the male reproductive system has not been effectively evaluated. To address this, we integrated RNA-seq, serum metabolomics and intestinal 16â¯S rDNA analysis to conduct a comprehensive investigation on the male reproductive system. The results showed that COS has potential targets for the treatment of oligospermia, which can promote the expression of meiotic proteins DDX4, DAZL and SYCP1, benefit germ cell proliferation and testicular development, enhance antioxidant capacity, and increase the expression of testicular steroid proteins STAR and CYP11A1. At the same time, COS can activate PI3K-Akt signaling pathway in testis and TM3 cells. Microbiome and metabolomics analysis suggested that COS alters gut microbial community composition and cooperates with serum metabolites to regulate spermatogenesis. Therefore, COS promotes male reproduction by regulating intestinal microorganisms and serum metabolism, activating PI3K-Akt signaling pathway, improving testicular antioxidant capacity and steroid regulation.
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This study investigated the effect of heat treatments on the pungency and aroma profiles of a spice oleoresin blend, and the emulsion stability with different surfactants, encapsulating agents, and homogenization mechanisms. Total pungency increased with heat until 120 °C and drastically reduced at 150 °C. Thermal processing induced aroma release, and 46 compounds were identified at 90 °C, predominantly comprising sesquiterpenes. Tween 80 dispersed the highest oleoresin mass (6.21 ± 0.31 mg/mL) and reported the maximum emulsion stability index. The oleoresin percentage significantly influenced the emulsion stability, with 1% oleoresin producing the most stable emulsion. High-pressure homogenization applied on gum Arabic resulted in a greater encapsulation efficiency, exceeding 86%, and the lowest creaming index (4.70 ± 0.06%), while Hi-Cap 100 produced the best flow properties. The findings provide insights into incorporating lipophilic spice oleoresin blends in aqueous food systems and understanding the release of flavor compounds during thermal food processing.
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As the core of a hypersonic propulsion system, the effective mixing efficiency of fuel and air in a supersonic combustor is crucial for its performance. This study focuses on a cold supersonic flow and employs computational fluid dynamics (CFD) techniques combined with Euler-Lagrange method's discrete-phase model (DPM) for multiphase flows, K-H and R-T (Kelvin-Helmholtz and Rayleigh-Taylor) mixing and atomization models, turbulence models, and surface evaporation models to investigate the injection, atomization, and mixing characteristics of kerosene in supersonic airflow. In order to enhance the mixing efficiency between kerosene and air while reducing flow losses, this study examines a staggered dual-jet injection scheme, with the dual jets arranged at the center of the cavity and having a dual-jet spacing of 10 and 20 mm, respectively. Starting from the interaction mechanism between jets, the impact of different staggered dual-jet spacings on the kerosene jet penetration height, span expansion area, angle of the shock wave, and Sauter mean diameter distribution was analyzed. The results show that a short dual-jet spacing (10 mm) leads to greater penetration height, wider span expansion, and a larger angle of the shock wave. When the dual-jet spacing is shorter, the interaction between the fuel jet and the cavity shear layer is stronger, resulting in an improved fuel mixing efficiency. The achievements of this study are consistent with previous experimental measurements and the literature, demonstrating a strong theoretical foundation for optimizing the design of hypersonic engines by deepening the understanding of the fundamental atomization mechanisms of kerosene jets in cold-state supersonic flows. Moreover, these results hold practical significance in improving the efficiency of kerosene combustion and enhancing the performance of flame stabilization devices.
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BACKGROUND: ICU nurses provide critical care and meticulously document electronic medical records (EMRs), tracking vital signs, interventions, and medication hourly. Despite China's ICUs effectively integrating real-time monitor and ventilator data into EMRs, challenges persist. Patient movements can introduce inaccuracies, and the demands of critical care may lead nurses to miss assessments like pain and nutrition. Traditional manual EMR verification is inefficient and error-prone, highlighting the urgent need for standardized, technology-aided EMR practices in ICU nursing. OBJECTIVE: This study aimed to describe the development and evaluation of an electronic medical records quality control system implemented in a Chinese tertiary care ICU setting, where current practices impact the accuracy of electronic medical records. METHODS: A prospective controlled trial was conducted with 600 ICU patients in Zhejiang Province from January to December 2023. An automated EMR quality control system was implemented in July 2023, facilitating real-time data collection and quality control for vital signs, medication management, and nursing evaluations. RESULTS: After implementing the ICU nursing electronic medical record quality control system, the prevalence of false data on vital signs decreased from 9 to 1.33%. Additionally, the incidence of incomplete medication administration dropped from 3.33 to 1.67%, and the rate of missing evaluations of assessment items in EMRs was reduced from 8 to 1.33%. Besides, the average time spent on quality control of the electronic medical records was 62 (48,76) seconds per record, which was significantly lower than the 264 (195.5,337.5) seconds using the traditional method. The nurses' satisfaction with the nursing electronic medical record quality control was (105.73 ± 9.31). CONCLUSIONS: The ICU nursing electronic medical record quality control system has led to substantial improvements in the quality and reliability of EMRs. The reduction in false data on vital signs, instances of incomplete medication administration, and missing evaluations of assessment items demonstrates the system's positive impact on nursing documentation practices. These improvements not only enhance the accuracy of patient records but also contribute to better patient care and safety within the ICU setting.
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Acupuncture can reduce blood pressure, heart rate (HR), and ameliorate cardiac damage by modulating the excitability of the sympathetic nervous system, but the exact mechanism of this effect remains unclear. This study investigated the potential mechanisms of acupuncture in the treatment of cardiac damage in hypertension. Spontaneously hypertensive rats (SHR) were used as the hypertension model with Wistar-Kyoto rats as the control. Manual acupuncture, electroacupuncture, and metoprolol were used as interventions. Systolic and diastolic blood pressure (SBP, DBP) plus HR were monitored with cardiac structure determined using Masson staining. Angiotensin II (Ang II) and norepinephrine in myocardium were detected with ELISA as was Ang(1-7) and gamma aminobutyric acid (GABA) in the rostral ventrolateral medulla (RVLM). Expression of mRNA for collagen type I (Col-I), Col-III, actin α1 (ACTA1), and thrombospondin 4 (THBS4) in myocardium was detected using real-time PCR. Expression of angiotensin converting enzyme (ACE), Ang II, angiotensin II type 1 receptor (AT1R), ACE2, and Mas receptor (MasR) proteins in RVLM was monitored using western blot. After manual acupuncture and electroacupuncture treatment, SHRs showed decreased SBP, DBP and HR, reduced myocardial damage. There was decreased expression of the ACE/Ang II/AT1R axis, and increased expression of the ACE2/Ang(1-7)/MasR axis within the RVLM. GABA levels were increased within the RVLM and norepinephrine levels were decreased in myocardial tissue. Metoprolol was more effective than either manual acupuncture or electroacupuncture. Acupuncture directed against hypertensive cardiac damage may be associated with regulation of ACE/Ang II/AT1R and the ACE2/Ang(1-7)/MasR pathway within the RLVM to reduce cardiac sympathetic excitability.
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Terapia por Acupuntura , Angiotensina II , Angiotensina I , Enzima Convertidora de Angiotensina 2 , Hipertensión , Bulbo Raquídeo , Fragmentos de Péptidos , Peptidil-Dipeptidasa A , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Receptor de Angiotensina Tipo 1 , Animales , Angiotensina I/metabolismo , Hipertensión/metabolismo , Hipertensión/terapia , Fragmentos de Péptidos/metabolismo , Enzima Convertidora de Angiotensina 2/metabolismo , Masculino , Receptor de Angiotensina Tipo 1/metabolismo , Receptor de Angiotensina Tipo 1/genética , Bulbo Raquídeo/metabolismo , Angiotensina II/metabolismo , Terapia por Acupuntura/métodos , Peptidil-Dipeptidasa A/metabolismo , Peptidil-Dipeptidasa A/genética , Proto-Oncogenes Mas , Sistema Nervioso Simpático/metabolismo , Ratas , Proteínas Proto-Oncogénicas/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Presión Sanguínea/fisiología , Transducción de Señal/fisiologíaRESUMEN
BACKGROUND: Psychiatric comorbidities are common in Multiple Sclerosis (MS) and are increasingly recognised in Aquaporin-4-Antibody Neuromyelitis Optica Spectrum Disorders (AQP4-Ab NMOSD) and Myelin Oligodendrocyte Glycoprotein-Antibody Associated Disease (MOGAD). However, it is unclear if these psychiatric comorbidities predate neurological diagnosis or classical neurological symptoms that are conventionally used to establish the onset of these central nervous system inflammatory demyelinating diseases. We sought to: (1) assess the frequency and incidence of psychiatrist-diagnosed psychiatric disorders before and after formal MS, AQP4-Ab NMOSD, and MOGAD diagnosis, and (2) identify potential factors associated with the presence of pre-existing psychiatric morbidity and depression severity at the first clinical visit for MS patients. METHODS: A retrospective observational study was performed on MS, AQP4-Ab NMOSD, and MOGAD patients seen at the National Neuroscience Institute (NNI) Singapore. Individuals with psychiatrist-diagnosed psychiatric disorders before and after neurological diagnosis were identified. Demographic, clinical data, and Patient Health Questionnaire (PHQ)-9 score at first clinic visit were collected and analysed. RESULTS: Three hundred and ninety-nine patients (249 MS, 102 AQP4-Ab NMOSD, 48 MOGAD) were included. A higher proportion of MS patients (13/249, 5.2%) had psychiatric disorders before neurological diagnosis, compared to AQP4-Ab NMOSD (1/102, 1.0%) and MOGAD (0/48, 0.0%) (p = 0.054). Within MS patients, univariate logistic regression revealed that age, sex, race, MS subtype, initial MRI lesion load, and interval between classical MS symptom onset to MS diagnosis were not associated with pre-existing psychiatric disorders. Mean PHQ-9 score for MS patients at their first MS consult was 4.4 (cut-off for no/minimal depression is ≤4); no clinical factors were predictive of higher PHQ-9 scores on univariate linear regression. The proportion of MS patients (29/236, 12.2%) who developed psychiatric illness after neurological diagnosis was not different from AQP4-Ab NMOSD (9/101, 8.9%) (p > 0.999), while this was significantly higher compared to MOGAD (0/48, 0.0%) (p = 0.021). The incidence rate of psychiatric diseases after neurological diagnosis, accounting for follow up time, was also similar between MS and AQP4-Ab NMOSD (incidence rate ratio 1.2; 95% confidence interval 0.54 - 2.8; p = 0.689). CONCLUSION: There is a significant psychiatric burden prior to MS diagnosis compared to AQP4-Ab NMOSD and MOGAD. The increased frequency of psychiatric comorbidity after NMOSD diagnosis merits further study to investigate the determinants of this phenomenon.
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Acuaporina 4 , Autoanticuerpos , Esclerosis Múltiple , Glicoproteína Mielina-Oligodendrócito , Neuromielitis Óptica , Humanos , Femenino , Masculino , Acuaporina 4/inmunología , Neuromielitis Óptica/epidemiología , Neuromielitis Óptica/inmunología , Neuromielitis Óptica/diagnóstico , Adulto , Estudios Retrospectivos , Esclerosis Múltiple/epidemiología , Esclerosis Múltiple/diagnóstico , Persona de Mediana Edad , Glicoproteína Mielina-Oligodendrócito/inmunología , Autoanticuerpos/sangre , Trastornos Mentales/epidemiología , Trastornos Mentales/diagnóstico , Comorbilidad , Enfermedades Autoinmunes Desmielinizantes SNC/inmunología , Enfermedades Autoinmunes Desmielinizantes SNC/epidemiología , Enfermedades Autoinmunes Desmielinizantes SNC/diagnóstico , Enfermedades Autoinmunes Desmielinizantes SNC/sangreRESUMEN
While BCR::ABL1 tyrosine kinase inhibitors have transformed the treatment paradigm for chronic myeloid leukemia (CML), disease progression and treatment resistance due to BCR::ABL1-dependent and BCR::ABL1-independent mechanisms remain a therapeutic challenge. Natural compounds derived from plants have significantly contributed to cancer pharmacotherapy. This study investigated the efficacy of an active component of Leea indica, a local medicinal plant, in CML. Using high-performance liquid chromatography-electrospray ionization-mass spectrometry, a chemical constituent from L. indica extract was isolated and identified as gallic acid. Commercially obtained gallic acid was used as a chemical standard. Gallic acid from L. indica inhibited proliferation and induced apoptosis in CML cell lines, as did the chemical standard. Furthermore, gallic acid induced apoptosis and decreased the colony formation of primary CML CD34+ cells. The combination of isolated gallic acid or its chemical standard with BCR::ABL1 tyrosine kinase inhibitors resulted in a significantly greater inhibition of colony formation and cell growth compared to a single drug alone. Mechanistically, CML cells treated with gallic acid exhibited the disruption of multiple oncogenic pathways including ERK/MAPK, FLT3 and JAK/STAT, as well as impaired mitochondrial respiration. Rescue studies showed that gallic acid is significantly less effective in inducing apoptosis in mitochondrial respiration-deficient ρ0 cells compared to wildtype cells, suggesting that the action of gallic acid is largely through the inhibition of mitochondrial respiration. Our findings highlight the therapeutic potential of L. indica in CML and suggest that gallic acid may be a promising lead chemical constituent for further development for CML treatment.
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Apoptosis , Proliferación Celular , Proteínas de Fusión bcr-abl , Ácido Gálico , Leucemia Mielógena Crónica BCR-ABL Positiva , Mitocondrias , Inhibidores de Proteínas Quinasas , Transducción de Señal , Ácido Gálico/farmacología , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/metabolismo , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Proteínas de Fusión bcr-abl/antagonistas & inhibidores , Proteínas de Fusión bcr-abl/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Transducción de Señal/efectos de los fármacos , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Línea Celular TumoralRESUMEN
Medicinal mushrooms, such as Taiwanofungus camphoratus, Inonotus obliquus, and Tropicoporus linteus, have been used in traditional medicine for therapeutic purposes and promotion of overall health in China and many East Asian countries for centuries. Modern pharmacological studies have demonstrated the large amounts of bioactive constituents (such as polysaccharides, triterpenoids, and phenolic compounds) available in these medicinal mushrooms and their potential therapeutic properties. Due to the rising demand for the health-promoting medicinal mushrooms, various cultivation methods have been explored to combat over-harvesting of the fungi. Evidence of the robust pharmacological properties, including their anticancer, hypoglycemic, hypolipidemic, antioxidant, and antiviral activities, have been provided in various studies, where the health-benefiting properties of the medicinal fungi have been further proven through numerous clinical trials. In this review, the cultivation methods, available bioactive constituents, therapeutic properties, and potential uses of T. camphoratus, I. obliquus and T. linteus are explored.
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Hydrocolloids have proven effective in improving the texture of surimi gels, yet their application in plant-based seafood analogues remains underexplored. This study aimed to develop a hydrocolloid blend comprising methylcellulose (MC), curdlan gum (CG), and high-acyl gellan gum (GG) to achieve a surimi-like texture in plant-based fish cakes (PBFC) made from brown rice and pea protein isolates. The research showcased that higher MC concentration boosted protein powder's heated oil holding capacity, while CG concentration increments lowered it. However, heated water holding capacity remained stable despite changes in MC and GG levels. Incorporating hydrocolloids elevated PBFC moisture content, decreasing expressible moisture and oil amounts with rising MC, CG and GG concentrations. PBFC hardness increased with higher hydrocolloid levels and was influenced by temperature, while springiness remained unaffected. GG helped maintain storage modulus (G') during PBFC cooling at higher concentrations, whereas the opposite effect was observed for MC. Analytically, higher MC concentrations reduced protein digestibility, while increased GG concentrations appeared to enhance it. Microstructural analysis corroborated these findings, with more protein aggregates in PBFC containing 3.8% MC and fewer in PBFCs with 6% CG and 3% GG. Consumer evaluations indicated that PBFC formulated with 1% MC, 3% CG, and 1.5% GG matched the springiness of commercial surimi-tofu fish cake, though it received slightly lower overall liking scores. In conclusion, the combined use of these three hydrocolloids demonstrated the potential to enhance the physical properties of PBFC and modify protein digestibility, offering insights into the development of innovative plant-based seafood analogues.
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Leptospirosis is a zoonotic disease caused by the pathogenic spirochaetes of the genus Leptospira. It is a public health concern in the Pacific Islands and is considered endemic in Palau. However, information on the genotypes and serotypes of causative Leptospira spp. in the country is limited. In this study, we isolated leptospires and detected antileptospiral antibodies in dogs and pigs. The isolates were characterized using a serological method and whole-genome sequencing. Leptospira interrogans was isolated from five of the 20 symptomatic dogs and one of the 58 healthy pigs. Their serogroups were identified as Icterohaemorrhagiae and Pyrogenes; however, the serogroup of one isolate could not be determined. Anti-Leptospira antibodies were detected in 14.4% (26/181) of the dogs and 20% (10/50) of the pigs. The reactive serogroups in dogs and pigs were almost identical, except for the Panama serogroup. Core genome multilocus sequence typing revealed that five of the six core genome sequence types (cgSTs) were newly identified in this study. The cgSTs from the serogroup Icterohaemorrhagiae isolates belonged to the same group as the Copenhageni and Icterohaemorrhagiae serovars isolated in other countries, whereas no similar cgSTs were identified in the Pyrogenes or unidentified serogroup strains. We demonstrated a high incidence of canine and porcine leptospirosis and identified new L. interrogans genotypes (cgSTs) circulating in Palau. Further investigations are needed to determine whether dogs and pigs serve as maintenance hosts for newly identified L. interrogans genotypes and whether they pose a risk of leptospirosis transmission to humans.
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Enfermedades de los Perros , Leptospirosis , Enfermedades de los Porcinos , Animales , Leptospirosis/veterinaria , Leptospirosis/epidemiología , Leptospirosis/microbiología , Perros , Porcinos , Enfermedades de los Perros/microbiología , Enfermedades de los Perros/epidemiología , Enfermedades de los Porcinos/microbiología , Enfermedades de los Porcinos/epidemiología , Leptospira/genética , Leptospira/inmunología , Leptospira/clasificación , Leptospira/aislamiento & purificación , Leptospira interrogans/genética , Leptospira interrogans/inmunología , Leptospira interrogans/aislamiento & purificación , Leptospira interrogans/clasificación , Serogrupo , Secuenciación Completa del Genoma , Anticuerpos Antibacterianos/sangre , Genotipo , Tipificación de Secuencias MultilocusRESUMEN
Chrononutrition, an emerging body of evidence on the relationship between biological rhythms and metabolism, has been established to be associated with glycemic responses. However, the available evidence is inconsistent, due to protocol variations. Therefore, this review aims to summarize the findings on chrononutrition characteristics and their association with glycemic responses among adults. Systematic searches were conducted across six databases (PubMed, EBSCO Host, ProQuest Central, MEDLINE & Ovid, Scopus and Web of Science) to identify all relevant studies published from January 2012. Two reviewers independently screened the abstracts and full-text articles based on the inclusion and exclusion criteria. Details about population characteristics, study methods and key findings were extracted following the PRISMA-ScR guideline. The quality of selected studies was evaluated using the mixed methods appraisal tool. The searchers identified 49 studies eligible for analysis. The results showed that meal timing, particularly night-time eating and snacking were associated with glycemic responses. Regarding meal regularity, skipping breakfast may affect glycemic responses, but no clear conclusion was drawn about its effect on insulin. The association between meal frequency and glycemic responses was inconclusive. Night fasting duration and restricted eating window are potentially associated with glycemic responses. The current review extensively investigates the association between chrononutrition factors and glycemic responses in adults. However, more prospective cohort and interventional studies are needed to better understand this causal-effect relationship.
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Glucemia , Ritmo Circadiano , Humanos , Glucemia/metabolismo , Adulto , Ritmo Circadiano/fisiología , Conducta Alimentaria/fisiología , Comidas/fisiología , Insulina/sangre , Insulina/metabolismo , Factores de Tiempo , Ayuno/fisiologíaRESUMEN
Phosphate plays a vital role in spider silk spinning and has been utilized in numerous artificial silk spinning attempts to replicate the remarkable mechanical properties of natural silk fiber. Its application in artificial processes has, however, yielded varying outcomes. It is thus necessary to investigate the origins and mechanisms behind these differences. By using recombinant silk protein SC-ADF3 derived from the garden spider Araneus diadematus, here, we describe its conformational changes under various conditions, elucidating the effect of phosphate on SC-ADF3 silk protein properties and interactions. Our results demonstrate that elevated phosphate levels induce the irreversible conformational conversion of SC-ADF3 from random coils to ß-sheet structures, leading to decreased protein solubility over time. Furthermore, exposure of SC-ADF3 to phosphate stiffens already formed structures and reduces the ability to form new interactions. Our findings offer insights into the underlying mechanism through which phosphate-induced ß-sheet structures in ADF3-related silk proteins impede fiber formation in the subsequent phases. From a broader perspective, our studies emphasize the significance of silk protein conformation for functional material formation, highlighting that the formation of ß-sheet structures at the initial stages of protein assembly will affect the outcome of material forming processes.
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Fibroínas , Fosfatos , Seda , Arañas , Animales , Arañas/química , Fosfatos/química , Seda/química , Fibroínas/química , Fibroínas/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Ingeniería de Proteínas/métodos , Conformación Proteica en Lámina beta , Estructura Secundaria de ProteínaRESUMEN
Golden pompano is an important aquaculture product in the coastal regions of southern China, which is highly dependent on insulin-like growth factor (IGF) for various biological processes. The cDNAs of ToIGF1, ToIGF2, and ToIGF3 are 1718 bp, 1658 bp, and 2272 bp in length, respectively, with corresponding amino acid sequences of 185 aa, 215 aa, and 194 aa. These sequences consist of 5 parts, including the signal peptide, the B domain, the C domain, the A domain, the D domain, and the E domain, which are also found in other species. While ToIGF1 has no SSR polymorphism, ToIGF2 and ToIGF3 have 3 and 1 SSR polymorphism sites, respectively. In terms of tissue expression, ToIGF1 is predominantly expressed in the liver, ToIGF2 shows its highest expression in the gills, and ToIGF3 also shows its highest expression in the gills, but no expression in the liver and spleen. These tissue distribution results suggest that ToIGFs are not only present in growth-related tissues such as the brain, muscle, and liver, but also in reproductive tissues, tissues that regulate osmotic pressure, and tissues related to food intake. This observation is consistent with other bony fish species and highlights the extensive biological functions of ToIGFs that need to be further explored and exploited. In addition, the expression levels of ToIGFs were found to be different in the different dietary groups, including the pelleted food group, the frozen squid group, and the frozen fish group. In the pelleted diet group, ToIGF1 and ToIGF2 were highly expressed in the liver and intestinal tissues, followed by the frozen fish group. These results suggest that the type of diet can affect the body's energy metabolism by influencing tissue expression of growth-related genes, which in turn affects individual growth.
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Alimentación Animal , Animales , Alimentación Animal/análisis , Peces/genética , Peces/metabolismo , Somatomedinas/metabolismo , Somatomedinas/genética , Dieta/veterinaria , Secuencia de Aminoácidos , Proteínas de Peces/genética , Proteínas de Peces/metabolismo , Regulación de la Expresión Génica , Filogenia , Péptidos Similares a la InsulinaRESUMEN
The formation of phytoene by condensing two geranylgeranyl diphosphate molecules catalyzed by phytoene synthase (PSY) is the first committed and rate-limiting step in carotenoid biosynthesis, which has been extensively investigated in bacteria, land plants and microalgae. However, this step in macroalgae remains unknown. In the present study, a gene encoding putative phytoene synthase was cloned from the economic red alga Pyropia yezoensis-a species that has long been used in food and pharmaceuticals. The conservative motifs/domains and the tertiary structure predicted using bioinformatic tools suggested that the cloned PyPSY should encode a phytoene synthase; this was empirically confirmed by pigment complementation in E. coli. This phytoene synthase was encoded by a single copy gene, whose expression was presumably regulated by many factors. The phylogenetic relationship of PSYs from different organisms suggested that red algae are probably the progeny of primary endosymbiosis and plastid donors of secondary endosymbiosis.
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Geranilgeranil-Difosfato Geranilgeraniltransferasa , Filogenia , Rhodophyta , Rhodophyta/genética , Rhodophyta/enzimología , Geranilgeranil-Difosfato Geranilgeraniltransferasa/genética , Geranilgeranil-Difosfato Geranilgeraniltransferasa/metabolismo , Carotenoides/metabolismo , Escherichia coli/genética , Clonación Molecular , Algas Comestibles , PorphyraRESUMEN
To maintain protein homeostasis, X-box binding protein 1 (XBP1) undergoes splicing following the activation of the unfolded protein response (UPR) in response to endoplasmic reticulum (ER) stress. Although targeting ER stress represents a promising therapeutic strategy, a comprehensive understanding of XBP1 at the cellular level and the link between XBP1 and the innate nervous system is lacking. Here, TCGA pancancer datasets from 33 cancer types, scRNA pancancer datasets from 454 patients and bulk RNA-seq datasets from 155 paired esophageal squamous cell carcinoma (ESCC) patients were analyzed. To cope with ER stress, plasma cells tend to activate XBP1 after undergoing bacterial infection and inflammatory signaling from the innate immune system. Patients with high XBP1 expression in their plasma cells have a higher tumor grade and worse survival. However, activation of the innate immune system with increased XBP1 expression in plasma cells correlates with an increased lymphocyte ratio, indicative of a more robust immune response. Moreover, XBP1 activation appears to initiate leukocyte migration at the transcriptional level. Our study revealed that the XBP1-induced UPR could mediate the crosstalk between optimal acquired humoral immune responses and innate immunity in ESCC.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Inmunidad Innata , Células Plasmáticas , Respuesta de Proteína Desplegada , Proteína 1 de Unión a la X-Box , Humanos , Proteína 1 de Unión a la X-Box/genética , Proteína 1 de Unión a la X-Box/metabolismo , Neoplasias Esofágicas/inmunología , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/mortalidad , Carcinoma de Células Escamosas de Esófago/inmunología , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/patología , Células Plasmáticas/inmunología , Células Plasmáticas/metabolismo , Masculino , Femenino , Estrés del Retículo Endoplásmico/inmunología , Regulación Neoplásica de la Expresión Génica , Persona de Mediana Edad , Anciano , PronósticoRESUMEN
BACKGROUND: Emodin, a natural anthraquinone derivative found in various Chinese medicinal herbs, has been proved to be an effective therapeutic agent in the treatment of many diseases. However, its effect on lung injury after intestinal ischemia/reperfusion injury remains unknown. This research was designed to investigate whether emodin protects against intestinal ischemia/reperfusion-induced lung injury and to elucidate the underlying molecular mechanisms in vivo and in vitro. METHODS: Intestinal ischemia/reperfusion injury was induced by occluding the superior mesenteric artery in mice, and mouse lung epithelial-12 cells were subjected to oxygen-glucose deprivation and reoxygenation to establish an in vitro model. RESULTS: Our data indicated that emodin treatment reduced intestinal ischemia/reperfusion-induced oxidative stress, inflammation and apoptosis in lung tissues and alleviated lung injury. However, the protective effects of emodin on intestinal ischemia/reperfusion-induced lung injury were reversed by the protein kinase B inhibitor triciribine or the heme oxygenase-1 inhibitor tin protoporphyrin IX. The protein kinase inhibitor triciribine also downregulated the expression of heme oxygenase-1. CONCLUSION: In conclusion, our data suggest that emodin treatment protects against intestinal ischemia/reperfusion-induced lung injury by enhancing heme oxygenase-1 expression via activation of the PI3K/protein kinase pathway. Emodin may act as a potential therapeutic agent for the prevention and treatment of lung injury induced by intestinal ischemia/reperfusion.
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Emodina , Hemo-Oxigenasa 1 , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Daño por Reperfusión , Transducción de Señal , Regulación hacia Arriba , Animales , Emodina/farmacología , Emodina/uso terapéutico , Daño por Reperfusión/prevención & control , Daño por Reperfusión/metabolismo , Daño por Reperfusión/etiología , Daño por Reperfusión/tratamiento farmacológico , Ratones , Proteínas Proto-Oncogénicas c-akt/metabolismo , Hemo-Oxigenasa 1/metabolismo , Masculino , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacos , Intestinos/irrigación sanguínea , Intestinos/patología , Intestinos/efectos de los fármacos , Ratones Endogámicos C57BL , Lesión Pulmonar/etiología , Lesión Pulmonar/prevención & control , Lesión Pulmonar/metabolismo , Lesión Pulmonar/tratamiento farmacológico , Lesión Pulmonar/patología , Modelos Animales de Enfermedad , Estrés Oxidativo/efectos de los fármacos , Proteínas de la MembranaRESUMEN
INTRODUCTION: Liver fibrosis is a major cause of morbidity and mortality among in patients with chronic hepatitis. Radiomics, particularly of the spleen, may improve diagnostic accuracy and treatment strategies. External validations are necessary to ensure reliability and generalizability. METHODS: In this retrospective study, we developed 3 radiomics models using contrast-enhanced computed tomography scans from 167 patients with liver fibrosis (training group) between January 2020 and December 2021. Radiomic features were extracted from arterial venous, portal venous, and equilibrium phase images. Recursive feature selection random forest and the least absolute shrinkage and selection operator logistic regression were used for feature selection and dimensionality reduction. Performance was assessed by area under the curve, C-index, calibration plots, and decision curve analysis. External validation was performed on 114 patients from 2 institutions. RESULTS: Twenty-five radiomic features were significantly associated with fibrosis stage, with 80% of the top 10 features originating from portal venous phase spleen images. The radiomics models showed good performance in the validation cohort (C-indices 0.723-0.808) and excellent calibration. Decision curve analysis indicated clinical benefits, with machine learning-based radiomics models (Random Forest score and support vector machine based radiomics score) providing more significant advantages. DISCUSSION: Radiomic features offer significant benefits over existing serum indices for staging virus-driven liver fibrosis, underscoring the value of radiomics in enhancing diagnostic accuracy. Specifically, radiomics analysis of the spleen presents additional noninvasive options for assessing fibrosis, highlighting its potential in improving patient management and outcomes.
RESUMEN
BACKGROUND: Lipoprotein(a) (Lp[a]) is associated with an increased risk of myocardial infarction (MI). However, the mechanism underlying this association has yet to be fully elucidated. OBJECTIVES: This multicenter study aimed to investigate whether association between Lp(a) and MI risk is reinforced by the presence of low-attenuation plaque (LAP) identified by coronary computed tomography angiography (CCTA). METHODS: In a derivation cohort, a total of 5,607 patients with stable chest pain suspected of coronary artery disease who underwent CCTA and Lp(a) measurement were prospectively enrolled. In validation cohort, 1,122 patients were retrospectively collected during the same period. High Lp(a) was defined as Lp(a) ≥50 mg/dL. The primary endpoint was a composite of time to fatal or nonfatal MI. Associations were estimated using multivariable Cox proportional hazard models. RESULTS: During a median follow-up of 8.2 years (Q1-Q3: 7.2-9.3 years), the elevated Lp(a) levels were associated with MI risk (adjusted HR [aHR]: 1.91; 95% CI: 1.46-2.49; P < 0.001). There was a significant interaction between Lp(a) and LAP (Pinteraction <0.001) in relation to MI risk. When stratified by the presence or absence of LAP, Lp(a) was associated with MI in patients with LAP (aHR: 3.03; 95% CI: 1.92-4.76; P < 0.001). Mediation analysis revealed that LAP mediated 73.3% (P < 0.001) for the relationship between Lp(a) and MI. The principal findings remained unchanged in the validation cohort. CONCLUSIONS: Elevated Lp(a) augmented the risk of MI during 8 years of follow-up, especially in patients with LAP identified by CCTA. The presence of LAP could reinforce the relationship between Lp(a) and future MI occurrence.