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The extrusion process, a vital technique for starch modification, is notably influenced by the moisture content (MC). This study aimed to elucidate the effect of varying MC levels (18, 22, 26, and 30%) on the structural and physicochemical characteristics of cassava flour during extrusion. Extrusion resulted in the fraction of degree of polymerization 13‒24, degree of branching, and molecular weight increased with increasing MC, with values of above indexes being 32.29%, 1.05%, and 1.21 × 105 g/mol, respectively, at a MC of 18%. This suggested that the degradation of amylopectin and amylose. Additionally, there was an increase in rapidly digestible starch (RDS) and a decrease in slowly digestible starch (SDS) in the extrudates in comparison to the native cassava flour. The extrusion of cassava flour at 18% MC exhibited the highest levels of RDS and SDS, reaching 64.52% and 4.06%, respectively. These findings indicated that low moisture extrusion could be a more effective method for disrupting the structure of cassava starch and enhancing the digestibility of cassava flour, offering valuable insights for the optimized use of cassava extrudates in various applications.

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The study aimed to investigating the mechanisms of relieved intestinal barrier damage by dynamic high-pressure microfluidization assisted with galactooligosaccharide- glycated whey protein isolate. The modifications changed the multi-structure, and the modified whey protein isolate could promote the proliferation of IEC-6 cells and contributed to the restoration of LPS-induced occludin damage in IEC-6 cells. Also, it could repair cyclophosphamide-induced ileal villus rupture and crypt destruction in BALB/c mice, significantly altered the abundance of dominant bacteria, which were associated with propionic acid, butyric acid, isovaleric acid, and valeric acid. Ileum transcriptomics revealed that the modified whey protein isolate significantly regulate of the levels of Cstad, Cyp11a1, and Hs6st2 genes, relating to the increase of propionic acid, isovaleric acid, and valeric acid. In conclusion, galactooligosaccharide- modified whey protein isolate could regulate the level of Cstad, Cyp11a1 and Hs6st2 genes by altering the gut microbial structure and the level of SCFAs, thereby repairing the intestinal barrier.

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Triplophysa grahami Regan 1906 is a member of the family Nemacheilidae, Cypriniformes, and native loach in Yunnan. In this study, the complete mitochondrial genome (mitogenome) of T. grahami Regan 1906 was firstly reported and analyzed. The mitogenome of T. grahami Regan 1906 is 16,566 bp in length, including 13 protein-coding genes (PCGs), 22 transfer RNAs (tRNAs), two ribosomal RNAs (rRNAs), and one control region (D-loop). The arrangement and orientation of protein coding genes and RNAs in T. grahami Regan 1906 are identical to other species of Nemacheilidae. The base composition of T. grahami Regan 1906 mitogenome was 29.25% A, 28.55% T, 25.03% C, and 17.17% G. The phylogenetic analysis based on the mitogenome showed that T. grahami Regan 1906 belongs to the clade of genus Triplophysa and the monophyly of Triplophysa is identified. This study contributed valuable genetic data for T. grahami Regan 1906 and explored the phylogenetic relationships in Nemacheilidae.

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Global climate change and rapid urbanization have resulted in more frequent and intense rainfall events in urban areas, raising concerns about the effectiveness of stormwater bioretention systems. In this study, we optimized the design by constructing a multi-layer filler structure, including plant layer, biochar layer, and pyrite layer, and evaluated its performance in nitrogen (N) and phosphorus (P) removal under different temperatures (5-18 °C and 24-43 °C), rainfall intensity (47.06 mm rainfall depth), and frequency (1-5 days rainfall intervals) conditions. The findings indicate that over 775 days, the plant system consistently removed 62.3% of total nitrogen (TN) and 97.0% of total phosphorus (TP) from 103 intense rainfall events. Temperature fluctuations had minimal impact on nitrate nitrogen (NO3--N) and TP removal, with differences in removal rates of only 1.0% and 0.6%, respectively, among plant groups. Across the multi-layer structure, plant roots mitigated the impact of temperature differences on NO3--N removal, while high-frequency rainfall fluctuated the stability of NO3--N removal. Dense plant roots reinforced N and P removal by facilitating denitrification in the vadose zone (biochar) and strengthening denitrification processes. Biochar and pyrite contributed to stable microenvironments and diverse ecological functions, enhancing NO3--N and PO43- removal. In summary, the synergistic effects of the multi-layer filler structure improved and stabilized N and P removal, providing valuable insights for addressing runoff pollution in bioretention systems amidst rapid urbanization and climate change challenges.

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The effect of whey protein isolate (WPI)- galacto-oligosaccharides (GOS)/fructo-oligosaccharides (FOS) conjugates on RAW264.7 cells, and further the effect of WPI-GOS conjugates on CTX-induced immunosuppressed mice were investigated. Compared to WPI-FOS conjugates, WPI-GOS conjugates exhibited deeper glycation extent, more pronounced structural unfolding and helix-destabilizing, and obviously improved functional indicators of RAW264.7 macrophages. In addition, WPI-GOS conjugates also repaired immune organ and intestinal barrier and increased IL-1ß and IFN-γ levels in immunosuppressed mice. The alteration of gut microbiota induced by WPI-GOS conjugates changed the serum metabolites, causing the activation of NFκB pathway, which strengthens the immune system. The activation of NFκB pathway maybe associated with the mTOR signal pathway and ABC transporters. However, the precise mechanisms by which NFκB pathway interacts with mTOR signal pathway and ABC transporters to modulate the immune response need for further research.

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Ciclofosfamida , FN-kappa B , Oligosacáridos , Proteína de Suero de Leche , Animales , Ratones , Ciclofosfamida/farmacología , Oligosacáridos/farmacología , Oligosacáridos/química , Proteína de Suero de Leche/química , Proteína de Suero de Leche/farmacología , Células RAW 264.7 , FN-kappa B/metabolismo , Terapia de Inmunosupresión , Microbioma Gastrointestinal/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Masculino , Serina-Treonina Quinasas TOR/metabolismo

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The high starch content and cost-effectiveness of cassava make it an attractive adjunct in beer brewing, with the fine structure of starch playing a crucial role in determining the composition of fermentable sugars (FS) and overall beer quality. This study investigated the effect of extrusion-induced changes in the starch structure of cassava flour on the FS profile of the wort and, consequently, on the quality attributes of cassava beer. The findings revealed that the shear stress during extrusion significantly reduced the molecular weight to 1.20 × 105g/mol and the branching degree of amylopectin. Simultaneously, there was an increase in the concentrations of short- and intermediate- chain amylose by 5.61% and 42.72%, respectively. These structural changes enhanced the enzymatic hydrolysis of extruded cassava flour (ECF), resulting in a higher total fermentable sugars content (22.00g/100 mL) in the ECF wort, predominantly composed of maltose and glucose. Furthermore, the altered FS profile led to an increased production of higher alcohols and esters in extruded cassava beer (ECB), particularly noted for the elevation of 2-phenylethyl alcohol levels, which imparted a distinctive rose aroma to the ECB. Consequently, the sensory profile of ECB showed significant improvement. This study offers critical insight into optimizing cassava beer quality and broadens the potential applications of cassava flour in the brewing industry.

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Cerveza , Fermentación , Manihot , Almidón , Manihot/química , Cerveza/análisis , Almidón/química , Azúcares/análisis , Harina/análisis , Amilosa/análisis , Amilosa/química , Hidrólisis , Amilopectina/química

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This research explored the impact of incorporating various levels of whole soybean pulp (WSP) (10%, 20%, 30%, 40%, and 50%) into wheat flour on the physical and nutritional qualities of steamed bread. In comparison with the traditional steamed bread, the substitution of up to 20% WSP did not significantly alter the specific volume, hardness, and chewiness of the steamed bread. Additionally, the crumb texture of the steamed bread with 20% WSP maintained small and uniform pores, with optimal springiness and cohesiveness. Nutritionally, the substitution of 10%-50% WSP enhanced total dietary fiber, total phenolics, and protein by 9.40%-89.79%, 14.96%-116.31%, and 3.45%-34.36%, respectively. Isoflavones in the steamed bread increased markedly from 22.92 µg/g to a range of 140.12-997.12 µg/g. The expected glycemic index showed a decrease from 90.24 to between 85.85 and 70.75, whereas amino acid scores improved from 59.22 to a range of 64.58-65.08, with lysine (Lys) scores notably increasing from 59.22 to between 64.96 and 88.80. In conclusion, partially replacing wheat flour with WSP is an effective method for enhancing the nutritional profile and addressing the essential amino acid imbalance in steamed bread. PRACTICAL APPLICATION: This study partially replaced flour with WSP to improve the steamed bread's nutritional quality. The optimal substitution level was determined to be 20% WSP, which improves the bread's nutritional value without significantly impacting its physical qualities. Furthermore, WSP is produced from soaked soybeans through hot water milling. This process simplifies soybean processing, lowers energy consumption and costs, and reduces pollution. It also effectively retains essential nutrients, such as protein, dietary fiber, polyphenols, and soy isoflavones, ensuring the full utilization of soybeans.

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The design of novel energetic compounds constitutes a pivotal research direction within the field of energetic materials. However, exploring the intricate relationship between their molecular structure and properties, in order to uncover their potential applications, remains a challenging endeavor. Therefore, employing multi-molecule assembly techniques to modulate the structure and performance of energetic materials holds immense significance. This approach enables the creation of a new generation of energetic materials, fueling research and development efforts in this field. In this study, a series of coordination compounds are synthesized by utilizing tetranitroethide (TNE) as an anion, which possesses a high nitrogen and oxygen content. The synthesis involves the synergistic modification between metal ions and small molecule ligands. Characterization of the obtained compounds is carried out using various techniques, including single crystal X-ray diffraction, IR spectroscopy, elemental analysis, and simultaneous TG-DSC analysis. Additionally, the energy of formation for these compounds is calculated using bomb calorimetry, based on the heat of combustion. The detonation performances of the compounds are determined through calculations using the EXPLO 5 software, and their sensitivities to external stimuli are evaluated.

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Objective: To explore the association between the quantity of hibernating myocardium (HM) and collateral circulation in patients with coronary chronic total occlusion (CTO). Materials and methods: 88 CTO patients were retrospectively analyzed who underwent evaluation for HM using both 99mTc-sestamibi Single photon emission computed tomography (99mTc-MIBI SPECT) myocardial perfusion imaging (MPI) combined with 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) myocardial metabolism imaging (MMI). They were divided into two groups according Rentrop grading: the poorly/well-developed collateral circulation group (PD/WD group, Rentrop grades 0-1/2-3). After adjusting for the potential confounding factors and conducting a stratified analysis, we explored the association between the HM index within CTO region and the grading of collateral circulation. Results: In the WD group, the HM index was notably higher than PD group (46.2 ± 15.7% vs. 20.9 ± 16.7%, P < 0.001). When dividing the HM index into tertiles and after adjusting for potential confounders, we observed that the proportion of patients with WD rose as the HM index increased (OR: 1.322, 95% CI: 0.893-1.750, P < 0.001), the proportion of patients with WD was 17.4%, 63.3%, and 88.6% for Tertile 1 to Tertile 3.This increasing trend was statistically significant (OR: 1.369, 95% CI: 0.873-1.864, P < 0.001), especially between Tertile 3 vs. Tertile 1 (OR: 4.330, 95% CI: 1.459-12.850, P = 0.008). Curve fitting displaying an almost linear positive correlation between the two. Conclusion: The HM index within CTO region is an independent correlation factor for the grading of coronary collateral circulation. A greater HM index corresponded to an increased likelihood of WD.

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The uneven formation of lithium dendrites during electroplating/stripping leads to a decrease in the utilization of active lithium, resulting in poor cycling stability and posing safety hazards to the battery. Herein, introducing a 3D continuously interconnected zirconium-based metal-organic framework (MOF808) network into a polyethylene oxide polymer matrix establishes a synergistic mechanism for lithium dendrite inhibition. The 3D MOF808 network maintains its large pore structure, facilitating increased lithium salt accommodation, and expands anion adsorption at unsaturated metal sites through its diverse large-space cage structure, thereby promoting the flow of Li+. Infrared-Raman and synchrotron small-angle X-ray scattering results demonstrate that the transport behavior of lithium salt ion clusters at the MOF/polymer interface verifies the increased local Li+ flux concentration, thereby raising the mobility number of Li+ to 0.42 and ensuring uniform Li+ flux distribution, leading to dendrite-free and homogeneous Li+ deposition. Furthermore, nanoindentation tests reveal that the high modulus and elastic recovery of MOF-based polymer electrolytes contribute to forming a robust, dendrite-resistant interface. Consequently, in symmetric battery systems, the system exhibits minimal overpotential, merely 35 mV, while maintaining stable cycling for over 1800 h, achieving low-overpotential lithium deposition. Moreover, it retains redox stability under high voltages up to 5.3 V.

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Human papillomavirus (HPV) 11/16 E6/E7 proteins have been recognized to be pivotal in viral pathogenesis. This study sought to uncover the potential mechanisms of how HPV11/16 E6/E7-transfected keratinocytes inhibit cytokine secretion in peripheral blood mononuclear cells (PBMC). Upon co-culturing HPV11/16 E6/E7-transfected keratinocytes with PBMC in a non-contact manner, we observed a marked decrease in various cytokines secreted by PBMC. To determine if this suppression was mediated by specific common secreted factors, we conducted transcriptomic sequencing on these transfected cells. This analysis identified 53 common differentially secreted genes in all four HPV-transfected cells. Bioinformatics analysis demonstrated these genes were predominantly involved in immune regulation. Results from quantitative PCR (qPCR) and an extensive literature review suggested the downregulation of 12 genes (ACE2, BMP3, BPIFB1, CLU, CST6, CTF1, HMGB2, MMP12, PDGFA, RNASE7, SULF2, TGM2), and upregulation of 7 genes (CCL17, CCL22, FBLN1, PLAU, S100A7, S100A8, S100A9), may be crucial in modulating tumor immunity and combating pathogenic infections, with genes S100A8 and S100A9, and IL-17 signaling pathway being particularly noteworthy. Thus, HPV11/16 E6/E7 proteins may inhibit cytokine secretion of immune cells by altering the expression of host-secreted genes. Further exploration of these genes may yield new insights into the complex dynamics of HPV infection.

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Citocinas , Leucocitos Mononucleares , Proteínas Oncogénicas Virales , Humanos , Citocinas/metabolismo , Citocinas/genética , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/virología , Leucocitos Mononucleares/metabolismo , Proteínas Oncogénicas Virales/genética , Proteínas Oncogénicas Virales/metabolismo , Proteínas Oncogénicas Virales/inmunología , Queratinocitos/virología , Queratinocitos/inmunología , Queratinocitos/metabolismo , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/inmunología , Papillomavirus Humano 11/genética , Papillomavirus Humano 11/inmunología , Perfilación de la Expresión Génica , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/inmunología , Infecciones por Papillomavirus/genética , Proteínas E7 de Papillomavirus/genética , Proteínas E7 de Papillomavirus/metabolismo , Proteínas E7 de Papillomavirus/inmunología , Técnicas de Cocultivo , Interacciones Huésped-Patógeno/inmunología , Interacciones Huésped-Patógeno/genética

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INTRODUCTION: This study aimed to explore ocular manifestations in ANCA-associated vasculitis (AAV), focusing on granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA), and microscopic polyangiitis (MPA) and to examine the associations with laboratory parameters and other systemic manifestations. METHODS: This retrospective study reviewed data from 533 AAV patients across two major Chinese medical centers from January 2016 to November 2023. Data including diagnosis, cranial manifestations of disease, ocular complications, and laboratory parameters were analyzed. Univariate and multivariable logistic regression analyses assessed associations across disease manifestations. Machine learning models were also utilized to predict the risk of retinal/eye involvement in AAV patients. RESULTS: Among 533 patients (210 GPA, 217 MPA, 99 EGPA, and 7 unclassified AAV), ocular complications were observed in 20.64% of them, with a distribution of 36.67% in GPA, 7.37% in MPA, and 18.18% in EGPA. The most common ocular manifestations included scleritis and retro-orbital mass/dacryocystitis, which were notably prevalent in GPA patients. Retinal involvement was observed in 9.09% of EGPA cases. The machine learning models yielded that eosinophil percentage (EOS%), high-sensitivity C-reactive protein (hsCRP), and CD4 + T cell/CD8 + T cell ratio (T4/T8) can predict retinal involvement. Furthermore, the white blood cell, EOS%, APTT, IgA, hsCRP, PR3-ANCA, and T4/T8 can predict eye involvement. CONCLUSION: Ocular manifestations are a prevalent complication across all forms of AAV. Predictive models developed through machine learning offer promising tools for early intervention and tailored patient care. This necessitates a multidisciplinary approach, integrating rheumatology and ophthalmology expertise for optimal patient outcomes.

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Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Oftalmopatías , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , Proteína C-Reactiva/análisis , China/epidemiología , Oftalmopatías/etiología , Granulomatosis con Poliangitis/complicaciones , Aprendizaje Automático , Poliangitis Microscópica/complicaciones , Estudios Retrospectivos , Escleritis/etiología , Escleritis/epidemiología

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PURPOSE: The etiology of asthma remains elusive, with no known cure. Based on accumulating evidence, autophagy, a self-degradation process that maintains cellular metabolism and homeostasis, participates in the development of asthma. Mycobacterium vaccae vaccine (M. vaccae), an immunomodulatory agent, has previously been shown to effectively alleviate airway inflammation and airway remodeling. However, its therapeutic effect on asthma via the regulation of autophagy remains unknown. Therefore, this study aimed to investigate the impact of M. vaccae in attenuating asthma airway inflammation via autophagy-mediated pathways. METHODS: Balb/c mice were used to generate an ovalbumin (OVA)-immunized allergic airway model and were subsequently administered either M. vaccae or M. vaccae + rapamycin (an autophagy activator) prior to each challenge. Next, airway inflammation, mucus secretion, and airway remodeling in mouse lung tissue were assessed via histological analyses. Lastly, the expression level of autophagy proteins LC3B, Beclin1, p62, and autolysosome was determined both in vivo and in vitro, along with the expression level of p-PI3K, PI3K, p-Akt, and Akt in mouse lung tissue. RESULTS: The findings indicated that aerosol inhalation of M. vaccae in an asthma mouse model has the potential to decrease eosinophil counts, alleviate airway inflammation, mucus secretion, and airway remodeling through the inhibition of autophagy. Likewise, M. vaccae could reduce the levels of OVA-specific lgE, IL-5, IL-13, and TNF-α in asthma mouse models by inhibiting autophagy. Furthermore, this study revealed that M. vaccae also suppressed autophagy in IL-13-stimulated BEAS-2B cells. Moreover, M. vaccae may activate the PI3K/Akt signaling pathway in the lung tissue of asthmatic mice. CONCLUSION: In summary, the present study suggests that M. vaccae may contribute to alleviating airway inflammation and remodeling in allergic asthma by potentially modulating autophagy and the PI3K/Akt signaling pathway. These discoveries offer a promising avenue for the development of therapeutic interventions targeting allergic airway inflammation.

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Asma , Autofagia , Inflamación , Mycobacteriaceae , Ovalbúmina , Transducción de Señal , Animales , Femenino , Ratones , Remodelación de las Vías Aéreas (Respiratorias)/inmunología , Asma/inmunología , Asma/terapia , Vacunas Bacterianas/inmunología , Modelos Animales de Enfermedad , Inflamación/inmunología , Pulmón/patología , Pulmón/inmunología , Ratones Endogámicos BALB C , Mycobacteriaceae/inmunología , Ovalbúmina/inmunología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/inmunología

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The global surge in antibiotic resistance genes (ARGs) presents a serious public health challenge. While methods like metagenomic analysis and qPCR arrays have been instrumental in investigating ARG distributions and dynamics, the vast diversity of ARGs often complicates effective monitoring and risk assessment. Here, we developed a High-Risk ARGs (HRA) chip based on high-capacity quantitative PCR array targeting previously identified high-risk ARGs. These ARGs are known to be prevalent in human-related environments, exhibit gene mobility, and are present in ESKAPE pathogens. The HRA chip include 101 primer sets and the 16S rRNA gene as a reference. These primer sets consist of 34 obtained from previous studies, and 67 newly designed primer sets which were validated in silico and experimentally. Absolute quantification of targeted ARGs is accomplished by generating standard curves for all ARGs with serially ten-fold diluted mixed plasmids containing targeted ARG sequences. The amplification efficiencies of all ARGs exceed 99% via plasmid template dilution tests, suggesting high reliability in quantification. The performance of HRA chip is further evaluated by practical applications in environmental samples from wastewater treatment plants (WWTPs) and soils with various land use types and fertilization regimes. The results indicate the dynamics of high-risk ARGs during wastewater treatment process, and reveal the profiles of soil high-risk ARGs which is distinct from those derived via metagenomic approaches. These findings highlight the potentials of HRA Chip in the evaluation of anthropogenic impacts on the environmental resistome with a more focused spectrum of high-risk ARGs. Overall, the HRA Chip emerges as a powerful and efficient high-throughput tool for rapid detection and quantification of high-risk ARGs, facilitating comprehensive profiling of high-risk resistomes in environmental samples which is essential for human health risk assessment of ARGs.

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Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , ARN Ribosómico 16S/genética , Farmacorresistencia Microbiana/genética , Monitoreo del Ambiente/métodos

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In this study examining the effects of temperature and dissolved oxygen (DO) on arsenic (As) release at the sediment-water interface (SWI), it was found that an increase in temperature promoted the formation of an anaerobic environment and the reduction and desorption of As fractions within the sediments. A temperature of 32 °C was the most favorable condition for As release at the SWI, and low DO conditions aggravated this process. Even under high DO conditions, the release of sediment As was significantly accelerated under high-temperature conditions, allowing dissolved As to rapidly migrate to the overlying water. In this process, the release of As from sediments was a consequence of the transformation of As fractions in the sediments.

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Background: Pheochromocytoma-induced takotsubo syndrome (Pheo-TTS) significantly increases the risk of adverse events for inpatient. The early identification of risk factors at admission is crucial for effective risk stratification and minimizing complications in Pheo-TTS patients. Methods: We conducted a systematic review combined with hierarchical cluster and feature importance analysis of demographic, clinical and laboratory data upon admission, alongside in-hospital complication data for Pheo-TTS patients. We analyzed cases published in PubMed and Embase from 2 May 2006 to 27 April 2023. Results: Among 172 Pheo-TTS patients, cluster analysis identified two distinct groups: a chest pain dominant (CPD) group (n = 86) and a non-chest pain dominant (non-CPD) group (n = 86). The non-CPD group was characterized by a younger age (44.0 ± 15.2 vs. 52.4 ± 14.4, p < 0.001), a higher prevalence of neurological/psychiatric disorders (53.5% vs. 32.6%), and increased presentation of dyspnea (87.2% vs. 17.4%), pulmonary rales (59.3% vs. 8.1%), and tachycardia (77.9% vs. 30.2%). Additionally, they exhibited more atypical takotsubo syndrome (TTS) imaging phenotypes (55.8% vs. 36.5%, all p < 0.05). The non-CPD group experienced more than a 2-fold increase for in-hospital adverse events compared to the CPD group (70.9% vs. 30.2%, p < 0.001). After adjusting for confounding factors, the absence of chest pain (odds ratio [OR] = 0.407, 95% confidence interval [CI] 0.169-0.979, p = 0.045), the presence of abdominal symptoms (OR = 3.939, 95% CI 1.770-8.766, p = 0.001), pulmonary rales (OR = 4.348, 95% CI 1.857-10.179, p = 0.001), and atypical TTS imaging phenotype (OR = 3.397, 95% CI 1.534-7.525, p = 0.003) remained as independent predictors of in-hospital complications. Conclusions: Clinical manifestations and imaging features at admission help to predict in-hospital complications for Pheo-TTS patients.

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The data element-driven industry (DEDI) generates large amounts of data, thereby mitigating information asymmetry. Does this affect corporate cash holdings? On the basis of theoretical analysis, this study empirically analyzes the impact of DEDI on enterprises' cash holdings and its transmission path using data of Chinese cities and A-share listed enterprises from 2008 to 2020. First, the results indicate that the DEDI reduces corporate cash holdings. As the development level of the DEDI improves, the corporate cash holdings gradually decrease. Second, the DEDI indirectly affects corporate cash holdings by influencing debt-financing and external credit supply capacities. Specifically, the DEDI increases the upstream corporate debt-financing and downstream corporate external credit supply capacities. Improvements in debt-financing and the external credit supply capacities can reduce corporate cash holdings. Third, the DEDI has a heterogeneous impact. For enterprise with CEO duality, small and medium-sized, and information technology enterprises, the impact of DEDI in reducing cash holdings is greater.

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BACKGROUND: The therapeutic potential of exosomes from human umbilical cord mesenchymal stem cells (HUMSCs-Exo) for delivering specific circular RNAs (circRNAs) in treating premature ovarian failure (POF) is not well understood. This study aimed to explore the efficacy of HUMSCs-Exo in delivering hsa_circ_0002021 for POF treatment, focusing on its effects on granulosa cell (GC) senescence and ovarian function. METHODS: Bioinformatic analysis was conducted on circRNA profiles using the GSE97193 dataset from GEO, targeting granulosa cells from varied age groups. To simulate granulosa cell senescence, KGN cells were treated with cyclophosphamide (CTX). HUMSCs were transfected with pcDNA 3.1 vectors to overexpress hsa_circ_0002021, and the HUMSCs-Exo secreted were isolated. These exosomes were characterized by transmission electron microscopy (TEM) and Western blotting to confirm exosomal markers CD9 and CD63. Co-culture of these exosomes with CTX-treated KGN cells was performed to assess ß-galactosidase activity, oxidative stress markers, ROS levels, and apoptosis via flow cytometry. Interaction between hsa_circ_0002021, microRNA-125a-5p (miR-125a-5p), and cyclin-dependent kinase 6 (CDK6) was investigated using dual-luciferase assays and RNA immunoprecipitation (RIP). A POF mouse model was induced with CTX, treated with HUMSCs-Exo, and analyzed histologically and via immunofluorescence staining. Gene expression was quantified using RT-qPCR and Western blot. RESULTS: hsa_circ_0002021 was under expressed in both in vivo and in vitro POF models and was effectively delivered by HUMSCs-Exo to KGN cells, showing a capability to reduce GC senescence. Overexpression of hsa_circ_0002021 in HUMSCs-Exo significantly enhanced these anti-senescence effects. This circRNA acts as a competitive adsorbent of miR-125a-5p, regulating CDK6 expression, which is crucial in modulating cell cycle and apoptosis. Enhanced expression of hsa_circ_0002021 in HUMSCs-Exo ameliorated GC senescence in vitro and improved ovarian function in POF models by modulating oxidative stress and cellular senescence markers. CONCLUSION: This study confirms that hsa_circ_0002021, when delivered through HUMSCs-Exo, can significantly mitigate GC senescence and restore ovarian function in POF models. These findings provide new insights into the molecular mechanisms of POF and highlight the therapeutic potential of circRNA-enriched exosomes in treating ovarian aging and dysfunction.

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Exosomas , Células de la Granulosa , Células Madre Mesenquimatosas , Insuficiencia Ovárica Primaria , ARN Circular , Cordón Umbilical , Insuficiencia Ovárica Primaria/terapia , Insuficiencia Ovárica Primaria/metabolismo , Insuficiencia Ovárica Primaria/genética , Femenino , Exosomas/metabolismo , Células Madre Mesenquimatosas/metabolismo , Humanos , Células de la Granulosa/metabolismo , ARN Circular/genética , ARN Circular/metabolismo , Animales , Cordón Umbilical/citología , Cordón Umbilical/metabolismo , Ratones , Senescencia Celular , Apoptosis , MicroARNs/genética , MicroARNs/metabolismo

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BACKGROUND: There are currently three strategies for the duration of LMWH lead-in before DOACs in patients with acute PE: one is at least 5 days, the other is at least 3 days, and the last one is less than 3 days. Which one is the best is yet unknown. METHODS: We divided non-high-risk PE patients into short-LMWH (LMWH <3 days), intermediate-LMWH (LMWH 3-5 days), and long-LMWH (LMWH >5 days) groups, in a 1:1:2 ratio by using propensity score matching. Primary outcomes were a composite of mortality including all-cause and PE-related mortality, VTE recurrence, and major bleeding, as well as each one of them, at 3-month after PE diagnosis. RESULTS: The short-LMWH group (N = 504) had higher 3-month composite primary outcome (129 [25.6%] vs 67 [13.3%], P < 0.001), all-cause mortality (112 [22.2%] vs 39 [7.7%], P < 0.001), and PE-related mortality (48 [9.5%] vs 17 [3.4%], P < 0.001), than the intermediate-LMWH group (N = 504). The short-LMWH group also had higher 3-month composite primary outcome (129 [25.6%] vs 151 [15.0%], P < 0.001), all-cause mortality (112 [22.2%] vs 90 [8.9%], P < 0.001), and PE-related mortality (48 [9.5%] vs 41 [4.1%], P < 0.001) than the long-LMWH group (N = 1008). The VTE recurrence and major bleeding rates were similar between the short-LMWH and intermediate-LMWH groups, and between the short-LMWH and long-LMWH groups. The intermediate-LMWH and long-LMWH groups had similar 3-month primary outcomes rates in whole or in part with each other. CONCLUSIONS: For patients with non-high-risk acute PE, the optimal duration of initial LMWH lead-in before switching to DOACs could be 3 to 5 days.

RESUMEN

OBJECTIVES: To investigate the structural characteristics of intestinal flora in children with sepsis and its association with inflammatory response. METHODS: A prospective cohort study was conducted. The children with sepsis who were admitted from December 2021 to January 2023 were enrolled as the sepsis group, and the children with non-sepsis who were admitted during the same period were enrolled as the non-sepsis group. The two groups were compared in terms of the distribution characteristics of intestinal flora, peripheral white blood cell count (WBC), C reactive protein (CRP), and cytokines, and the correlation of the relative abundance of fecal flora with WBC, CRP, and cytokines was analyzed. RESULTS: At the genus level, compared with the non-sepsis group, the sepsis group had significantly lower relative abundance of Akkermansia, Ruminococcus, and Alistipes and significantly higher relative abundance of Enterococcus, Streptococcus, and Staphylococcus (P<0.05). At the phylum level, Proteobacteria was the dominant phylum (37.46%) in the group of children with a score of ≤70 from the Pediatric Critical Illness Score (PICS), and Firmicutes was the dominant phylum in the group of children with a score of 71-80 or 81-90 from the PICS (72.20% and 43.88%, respectively). At the genus level, among the 18 specimens, 5 had a relative abundance of >50% for a single flora. Compared with the non-sepsis group, the sepsis group had significant higher levels of WBC, CRP, interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (P<0.05). The Spearman's rank correlation analysis showed that at the genus level, the relative abundance of Ruminococcus, Alistipes, and Parasutterella in the sepsis group was negatively correlated with the levels of WBC, CRP, and IL-6 (P<0.05); the relative abundance of Enterococcus was positively correlated with the CRP level (P<0.01); the relative abundance of Streptococcus and Staphylococcus was positively correlated with the levels of CRP and IL-6 (P<0.05); the relative abundance of Streptococcus was positively correlated with WBC (P<0.05). CONCLUSIONS: Intestinal flora disturbance is observed in children with sepsis, and its characteristics vary with the severity of the disease. The structural changes of intestinal flora are correlated with inflammatory response in children with sepsis.

Asunto(s)

Proteína C-Reactiva , Microbioma Gastrointestinal , Sepsis , Humanos , Sepsis/microbiología , Sepsis/sangre , Estudios Prospectivos , Masculino , Femenino , Preescolar , Proteína C-Reactiva/análisis , Lactante , Niño , Citocinas/sangre , Citocinas/análisis , Estudios de Cohortes , Recuento de Leucocitos , Inflamación