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1.
ACS Cent Sci ; 10(6): 1201-1210, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38947212

RESUMEN

Coacervates formed by liquid-liquid phase separation emerge as important biomimetic models for studying the dynamic behaviors of membraneless organelles and synchronously motivating the creation of smart architectures with the regulation of cell fate. Despite continuous progress, it remains challenging to balance the trade-offs among structural stability, versatility, and molecular communication for regulation of cell fate and systemic investigation in a complex physiological system. Herein, we present a self-stabilizing and fastener-bound gain-of-function methodology to create a new type of synthetic DNA membraneless organelle (MO) with high stability and controlled bioactivity on the basis of DNA coacervates. Specifically, long single-strand DNA generated by rolling circle amplification (RCA) is selected as the scaffold that assembles into membraneless coacervates via phase separation. Intriguingly, the as-formed DNA MO can recruit RCA byproducts and other components to achieve self-stabilization, nanoscale condensation, and function encoding. As a proof of concept, photoactivatable DNA MO is constructed and successfully employed for time-dependent accumulation and spatiotemporal management of cancer in a mouse model. This study offers new, important insights into synthetic membraneless organelles for the basic understanding and manipulation of important life processes.

2.
Artículo en Inglés | MEDLINE | ID: mdl-38878711

RESUMEN

OBJECTIVE: Optimize the extraction process of earthworm fibrinolytic enzyme. METHODS: Chinese common earthworms underwent a series of purification processes, including grinding, salting out, hydrophobic medium chromatography, ammonium sulfate precipitation, and ion exchange chromatography, to obtain purified earthworm fibrinolytic enzyme. RESULTS: Utilizing Pheretima aspergillum as the starting material, we discovered that the specific activity of lumbrokinase extracted via ammonium sulfate precipitation was 58 U/mg, noticeably surpassing that achieved through heat precipitation and ethanol precipitation methods. After undergoing two rounds of chromatographic separations employing hydrophobic affinity chromatography and anion exchange chromatography, the specific activity of the lumbrokinase protein soared to 9267 U/mg, significantly exceeding the 3,178 U/mg specific activity attained through industrial extraction methods. DISCUSSION: The development of a novel crude extraction method for lumbrokinase protein can significantly boost its activity and purity. The discovery of a high-efficiency purification method and the identification of protein components within highly active lumbrokinase pave the way for further investigations into these proteins.

3.
Inorg Chem ; 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38917357

RESUMEN

Chemiresistive NH3/NO2 sensors are attracting considerable attention for use in air-conditioning systems. However, the existing sensors suffer from cross-sensitivity, detection limit, and power consumption, owing to the inadequate charge-transfer ability of gas-sensing materials. Herein, we develop a flexible NH3/NO2 sensor based on graphitic carbon nitride/polypyrrole decorated alginate paper (AP@g-CN/PPy). The flexible sensor can work at room temperature and exhibits a positive response of 23-246% and a negative response of 37-262% toward 0.1-5 ppm of NH3 and NO2, which is ∼4.5 times and ∼7.0 times higher than a pristine PPy sensor. Moreover, the sensor exhibits flexibility, reproducibility, long-term stability, anti-interference, and high resilience to humidity, indicating its promising potential in real applications. Using the 9 feature parameters extracted from the transient response, a matched deep learning model was developed to achieve qualitative recognition of different types of gases with distinguished decision boundaries. This work not only provides an alternative gas-sensing material for dual NH3/NO2 sensing but also establishes an intelligent strategy to identify hazardous gases under an interfering atmosphere.

4.
Front Immunol ; 15: 1400046, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38887295

RESUMEN

Background: Kawasaki disease shock syndrome (KDSS) is a critical manifestation of Kawasaki disease (KD). In recent years, a logistic regression prediction model has been widely used to predict the occurrence probability of various diseases. This study aimed to investigate the clinical characteristics of children with KD and develop and validate an individualized logistic regression model for predicting KDSS among children with KD. Methods: The clinical data of children diagnosed with KDSS and hospitalized between January 2021 and December 2023 were retrospectively analyzed. The best predictors were selected by logistic regression and lasso regression analyses. A logistic regression model was built of the training set (n = 162) to predict the occurrence of KDSS. The model prediction was further performed by logistic regression. A receiver operating characteristic curve was used to evaluate the performance of the logistic regression model. We built a nomogram model by visualizing the calibration curve using a 1000 bootstrap resampling program. The model was validated using an independent validation set (n = 68). Results: In the univariate analysis, among the 24 variables that differed significantly between the KDSS and KD groups, further logistic and Lasso regression analyses found that five variables were independently related to KDSS: rash, brain natriuretic peptide, serum Na, serum P, and aspartate aminotransferase. A logistic regression model was established of the training set (area under the receiver operating characteristic curve, 0.979; sensitivity=96.2%; specificity=97.2%). The calibration curve showed good consistency between the predicted values of the logistic regression model and the actual observed values in the training and validation sets. Conclusion: Here we established a feasible and highly accurate logistic regression model to predict the occurrence of KDSS, which will enable its early identification.


Asunto(s)
Síndrome Mucocutáneo Linfonodular , Humanos , Síndrome Mucocutáneo Linfonodular/diagnóstico , Síndrome Mucocutáneo Linfonodular/sangre , Masculino , Femenino , Preescolar , Lactante , Estudios Retrospectivos , Modelos Logísticos , Niño , Choque/etiología , Choque/diagnóstico , Curva ROC , Nomogramas , Pronóstico , Biomarcadores/sangre
5.
Postgrad Med ; 136(4): 446-455, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38785198

RESUMEN

OBJECTIVES: Several parameters of widely used risk assessment tools for pulmonary arterial hypertension (PAH) have been linked to hemodynamic outcomes of balloon pulmonary angioplasty (BPA). Therefore, we aimed to determine whether these risk assessment tools could be used to predict hemodynamic outcomes following BPA. METHODS: In this retrospective study, we included 139 patients with chronic thromboembolic pulmonary hypertension who had undergone BPA at Center for Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College (Beijing, China). We compared the accuracies of seven well-validated risk assessment tools for predicting hemodynamic outcomes following BPA. A favorable hemodynamic outcome was defined as a mean pulmonary arterial pressure < 30 mmHg at follow-up. RESULTS: The baseline risk profiles varied significantly among the risk assessment tools. The US Registry to Evaluate Early and Long-Term PAH Disease Management risk scales and the French risk assessment tools rated most patients as high-risk, while the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) series and laboratory examination-based risk scales categorized most patients as having intermediate-risk profile. COMPERA 2.0 (4-strata) exhibited the highest predictive power among all risk stratifications. Noninvasive risk stratification (COMPERA 2.0 [3-strata]) showed a comparable predictive ability to that of invasive risk stratification (COMPERA 1.0) (area under the curve 0.649 vs. 0.648). Moreover, incorporating diffusing capacity of the lungs for carbon monoxide and tricuspid regurgitation velocity into COMPERA 2.0 (4-strata) further enhanced its predictive power (net reclassification index 0.153, 95% confidence interval 0.009-0.298, p = 0.038). Additionally, this refined COMPERA version had a high calibration accuracy (slope 0.96). CONCLUSION: Although the risk strata distribution varied among different risk assessment tools, the proportion of patients achieving favorable hemodynamics decreased with the escalation of risk stratification in most models. The well-validated risk assessment tools for PAH could also predict hemodynamic outcomes following BPA, and the refined COMPERA 2.0 model exhibited the highest predictive ability among these. Applying risk assessment tools before BPA can facilitate early identification of patients in need of closer monitoring and more intensive interventions, contributing to a better prognosis after BPA.


Asunto(s)
Angioplastia de Balón , Hemodinámica , Humanos , Masculino , Femenino , Medición de Riesgo/métodos , Angioplastia de Balón/métodos , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/terapia , Anciano , Embolia Pulmonar , Resultado del Tratamiento , Hipertensión Arterial Pulmonar/fisiopatología , China/epidemiología
6.
Cardiovasc Diabetol ; 23(1): 154, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38702735

RESUMEN

BACKGROUND: Insulin resistance (IR) plays an important role in the pathophysiology of cardiovascular disease. Recent studies have shown that diabetes mellitus and impaired lipid metabolism are associated with the severity and prognosis of idiopathic pulmonary arterial hypertension (IPAH). However, the relationship between IR and pulmonary hypertension is poorly understood. This study explored the association between four IR indices and IPAH using data from a multicenter cohort. METHODS: A total of 602 consecutive participants with IPAH were included in this study between January 2015 and December 2022. The metabolic score for IR (METS-IR), triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, triglyceride and glucose (TyG) index, and triglyceride-glucose-body mass index (TyG-BMI) were used to quantify IR levels in patients with IPAH. The correlation between non-insulin-based IR indices and long-term adverse outcomes was determined using multivariate Cox regression models and restricted cubic splines. RESULTS: During a mean of 3.6 years' follow-up, 214 participants experienced all-cause death or worsening condition. Compared with in low to intermediate-low risk patients, the TG/HDL-C ratio (2.9 ± 1.7 vs. 3.3 ± 2.1, P = 0.003) and METS-IR (34.5 ± 6.7 vs. 36.4 ± 7.5, P < 0.001) were significantly increased in high to intermediate-high risk patients. IR indices correlated with well-validated variables that reflected the severity of IPAH, such as the cardiac index and stroke volume index. Multivariate Cox regression analyses indicated that the TyG-BMI index (hazard ratio [HR] 1.179, 95% confidence interval [CI] 1.020, 1.363 per 1.0-standard deviation [SD] increment, P = 0.026) and METS-IR (HR 1.169, 95% CI 1.016, 1.345 per 1.0-SD increment, P = 0.030) independently predicted adverse outcomes. Addition of the TG/HDL-C ratio and METS-IR significantly improved the reclassification and discrimination ability beyond the European Society of Cardiology (ESC) risk score. CONCLUSIONS: IR is associated with the severity and long-term prognosis of IPAH. TyG-BMI and METS-IR can independently predict clinical worsening events, while METS-IR also provide incremental predictive performance beyond the ESC risk stratification.


Asunto(s)
Biomarcadores , Glucemia , Resistencia a la Insulina , Índice de Severidad de la Enfermedad , Triglicéridos , Adulto , Femenino , Humanos , Masculino , Biomarcadores/sangre , Glucemia/metabolismo , China/epidemiología , HDL-Colesterol/sangre , Progresión de la Enfermedad , Hipertensión Pulmonar Primaria Familiar/diagnóstico , Hipertensión Pulmonar Primaria Familiar/sangre , Hipertensión Pulmonar Primaria Familiar/fisiopatología , Hipertensión Pulmonar Primaria Familiar/mortalidad , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Triglicéridos/sangre
7.
Dalton Trans ; 53(22): 9540-9546, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38768259

RESUMEN

The construction of Cu-In bi-component catalysts is an effective strategy to enhance the electrocatalytic properties towards the CO2 reduction reaction (CO2RR). However, realizing the co-promotion of In and heteroatom P on the electrocatalytic performance is still a challenge due to the poor selectivity of metal phosphides. Herein, a novel bi-component catalyst (CuO-In(PO3)3/C) was successfully synthesized via a facile one-pot reaction to realize the integration of Cu, In, and P species for the enhancement of electrocatalysis. In particular, the as-obtained nanorod-like Cu-In(PO3)3/C exhibits superior electrocatalysis towards the CO2RR, with the highest Faraday efficiency of CO (FECO) of 88.5% at -0.586 V. Furthermore, Cu-In(PO3)3/C shows better activity, selectivity, and stability in the CO2RR; in particular, the total current density can reach 178.09 mA cm-2 at -0.886 V in 2.0 M KOH solution when a flow cell is employed. This work provides a reliable method for simplifying the synthesis of novel Cu-based catalysts and exploits the application of heteroatom P in the field of efficient CO2RR.

8.
Sci Rep ; 14(1): 8063, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38580834

RESUMEN

The mechanical properties of a coal-rock body were examined through uniaxial compression tests, and the rupture process of the coal-rock body was monitored in real time using a combined acoustic emission (AE) monitoring system and a digital image correlation (DIC) full-field strain measurement system. From a comparison of the mechanical properties of coal and sandstone, clear differences are apparent regarding the uniaxial compressive strength, deformation characteristics, and damage mode; the brittle failure characteristics of the coal samples are also more evident. The change in AE energy reflects the accumulation and release of elastic energy during the rupture process, and the evolution of AE localization points under different stress levels can effectively reflect rupture propagation. Further, the DIC full-field strain measurement method can quantitatively monitor the evolution of the displacement and strain fields at the marking point and surface simultaneously, thereby overcoming the limitations of traditional empirical and qualitative rupture processes. During monitoring, the AE focuses on the internal rupture of the specimen and the DIC focuses on the surface deformation. These complement each other and reflect the rupture process more comprehensively.

9.
BMC Pulm Med ; 24(1): 185, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38632547

RESUMEN

BACKGROUND: Patients with pulmonary arterial hypertension (PAH) exhibit a distinct gut microbiota profile; however, the causal association between gut microbiota, associated metabolites, and PAH remains elusive. We aimed to investigate this causal association and to explore whether dietary patterns play a role in its regulation. METHODS: Summary statistics of gut microbiota, associated metabolites, diet, and PAH were obtained from genome-wide association studies. The inverse variance weighted method was primarily used to measure the causal effect, with sensitivity analyses using the weighted median, weighted mode, simple mode, MR pleiotropy residual sum and outlier (MR-PRESSO), and MR-Egger methods. A reverse Mendelian randomisation analysis was also performed. RESULTS: Alistipes (odds ratio [OR] = 2.269, 95% confidence interval [CI] 1.100-4.679, P = 0.027) and Victivallis (OR = 1.558, 95% CI 1.019-2.380, P = 0.040) were associated with an increased risk of PAH, while Coprobacter (OR = 0.585, 95% CI 0.358-0.956, P = 0.032), Erysipelotrichaceae (UCG003) (OR = 0.494, 95% CI 0.245-0.996, P = 0.049), Lachnospiraceae (UCG008) (OR = 0.596, 95% CI 0.367-0.968, P = 0.036), and Ruminococcaceae (UCG005) (OR = 0.472, 95% CI 0.231-0.962, P = 0.039) protected against PAH. No associations were observed between PAH and gut microbiota-derived metabolites (trimethylamine N-oxide [TMAO] and its precursors betaine, carnitine, and choline), short-chain fatty acids (SCFAs), or diet. Although inverse variance-weighted analysis demonstrated that elevated choline levels were correlated with an increased risk of PAH, the results were not consistent with the sensitivity analysis. Therefore, the association was considered insignificant. Reverse Mendelian randomisation analysis demonstrated that PAH had no causal impact on gut microbiota-derived metabolites but could contribute to increased the levels of Butyricicoccus and Holdemania, while decreasing the levels of Clostridium innocuum, Defluviitaleaceae UCG011, Eisenbergiella, and Ruminiclostridium 5. CONCLUSIONS: Gut microbiota were discovered suggestive evidence of the impacts of genetically predicted abundancy of certain microbial genera on PAH. Results of our study point that the production of SCFAs or TMAO does not mediate this association, which remains to be explained mechanistically.


Asunto(s)
Microbioma Gastrointestinal , Metilaminas , Hipertensión Arterial Pulmonar , Humanos , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Hipertensión Pulmonar Primaria Familiar , Colina
10.
Food Chem X ; 22: 101380, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38665633

RESUMEN

In order to re-utilize the residual from the distillation of the Chinese wolfberry wine and reduce the environmental pollution, the residual is firstly filtered by the ceramic membrane of 50 nm, then the Cu (II) has transferred from the distillation is removed using the ion exchange resin, and the treated solution is recombined with the distilled liquor to make the Chinese wolfberry brandy and the comparison has conducted on the physicochemical properties, antioxidant activity and flavor compounds between the recombined brandy and the finished brandy. The results indicate that the Cu (II) was effectively removed by ceramic membrane combined with the D401 resin. Compared with finished brandy, the recombined brandy contains high contents of polysaccharides, phenols and flavonoids, thus contributing to the improvement of antioxidant capacity. The gas chromatography-ion mobility spectrometry (GC-IMS) reveals that 25 volatile compounds like esters and alcohols have identified in the brandy samples, and the differences are significant between the recombined and the finished brandy. In summary, the distilled residual from the Chinese wolfberry wine might be re-used after the appropriate treatment so as to reduce the discharge and environmental pollution.

11.
Sci Rep ; 14(1): 8522, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38609455

RESUMEN

To study the total particulate matter (TPM) in flue gas emitted by coking plants, a sampling system that could be used to collect filterable particulate matter (FPM) and condensable particulate matter (CPM) was designed and developed based on Method 202 recommended by the U.S. Environmental Protection Agency in 2017 and HJ 836-2017 issued by China. Using this system, FPM and CPM in flue gas emitted by four coking furnaces named A, B, C, and D were tested in China. Further, 9 water-soluble ions, 20 elements, and organic matter present in the CPM were simultaneously examined to determine their formation mechanisms. Statistical data suggested that the FPM emission level in the coking flue gas was low and the average mass concentration was less than 10 mg/m3. However, with high CPM and TPM emission levels, the TPM mass concentrations of A, B, C, and D were 130 ± 11.1, 84.4 ± 6.36, 35.1 ± 17.0, and 63.8 ± 13.0 mg/m3, respectively. The main component of TPM was CPM, and the average mass concentration of CPM accounted for 98%, 95%, 68%, and 95% of TPM in furnaces A, B, C, and D, respectively. Water-soluble ions were the important components of CPM, and the total concentration of water-soluble ions accounted for 70%, 87%, 42%, and 66% of CPM in furnaces A, B, C, and D, respectively. Toxic and harmful heavy metals, such as Mn, Cr, Ni, Cu, Zn, As, Cd, and Pb, were detected in CPM. The formation mechanism of CPM was analyzed in combination with flue-gas treatment. It was shown that the treatment process "activated carbon- flue-gas countercurrent-integrated purification technology + ammonia spraying" used in furnaces A and B was less effective in removing CPM, water-soluble ions, metals, and compounds than that of "selective catalytic reduction denitrification + limestone-gypsum wet desulfurization (spraying NaOH solution)" in furnaces C and D. Hence, different flue-gas treatment technologies and operation levels played vital roles in the formation, transformation, and removal of CPM from flue-gas. Organic components in CPM discharged from furnace A were determined via gas chromatography-mass spectrometry, and the top 15 organic components in CPM were obtained using the area normalization method. N-alkanes accounted for the highest proportion, followed by esters and phenols, and most of them were toxic and harmful to humans and ecosystems. Therefore, advanced CPM treatment technologies should be developed to reduce atmospheric PM2.5 and its precursors to improve ambient air quality in China.

12.
Respir Med ; 227: 107643, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38657739

RESUMEN

BACKGROUND: Emerging evidence has shown that the blood urea nitrogen to serum albumin ratio (BAR) is associated with the severity and prognosis of heart failure. However, its role in idiopathic pulmonary arterial hypertension (IPAH) remains unclear. This study investigated the associations between BAR and functional status, echocardiographic findings, hemodynamics, and long-term outcomes among patients with IPAH. METHODS: This study included consecutive patients who underwent right heart catheterization (RHC) and were diagnosed with IPAH between January 2013 and January 2018 at Fuwai Hospital. The primary outcome was the worsening of clinical symptoms. Spearman correlation coefficients were used to evaluate the association between the BAR and established markers of IPAH severity. Receiver operating characteristic (ROC) curve analysis was used to determine BAR's optimal cut-off and predictive performance. Kaplan-Meier analysis and Cox proportional hazard models assessed the relationship between BAR and clinical worsening. RESULTS: A total of 340 patients with IPAH were included in this study. BAR correlated with well-validated variables that reflected the severity of IPAH, such as World Health Organization functional class, 6-min walk distance, N-terminal pro-brain natriuretic peptide (NT-proBNP) level, mixed venous oxygen saturation, and cardiac index. Kaplan-Meier curves indicated that patients with BAR>3.80 had a significantly higher clinical worsening rate (log-rank test, P < 0.001) than those with BAR≤3.80. Multivariate Cox analysis showed that BAR could independently predict clinical worsening [hazard ratio(HR):2.642, 95 % confidence interval (CI):1.659-4.208, P < 0.001]. In addition, BAR provided additional predictive value for the European Society of Cardiology (ESC)/European Respiratory Society (ERS) risk assessment score. CONCLUSIONS: BAR reflects disease severity and is independently associated with the prognosis of patients with IPAH.


Asunto(s)
Biomarcadores , Nitrógeno de la Urea Sanguínea , Albúmina Sérica , Índice de Severidad de la Enfermedad , Humanos , Femenino , Masculino , Pronóstico , Biomarcadores/sangre , Albúmina Sérica/análisis , Albúmina Sérica/metabolismo , Persona de Mediana Edad , Adulto , Hipertensión Pulmonar Primaria Familiar/sangre , Hipertensión Pulmonar Primaria Familiar/fisiopatología , Hipertensión Pulmonar Primaria Familiar/diagnóstico , Ecocardiografía , Cateterismo Cardíaco , Hemodinámica/fisiología , Valor Predictivo de las Pruebas , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos
13.
Clin Transl Sci ; 17(3): e13751, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38450983

RESUMEN

Inflammation contributes to development of idiopathic pulmonary arterial hypertension (IPAH), and tumor biomarkers can reflect inflammatory and immune status. We aimed to determine the value of tumor biomarkers in IPAH comprehensively. We enrolled 315 patients with IPAH retrospectively. Tumor biomarkers were correlated with established indicators of pulmonary hypertension severity. Multivariable Cox regression found that AFP (hazard ratio [HR]: 1.587, 95% confidence interval [CI]: 1.014-2.482, p = 0.043) and CA125 (HR: 2.018, 95% CI: 1.163-3.504, p = 0.013) could independently predict prognosis of IPAH. The changes of AFP over time were associated with prognosis of patients, each 1 ng/mL increase in AFP was associated with 5.4% increased risk of clinical worsening (HR: 1.054, 95% CI: 1.001-1.110, p = 0.046), enabling detection of disease progression. Moreover, beyond well-validated PH biomarkers, CA125 was still of prognostic value in the low-risk patients (HR: 1.014, 95% CI: 1.004-1.024, p = 0.004), allowing for more accurate risk stratification and prediction of disease outcomes. AFP and CA125 can serve for prognosis prediction, risk stratification, and dynamic monitor in patients with IPAH.


Asunto(s)
Biomarcadores de Tumor , alfa-Fetoproteínas , Humanos , Hipertensión Pulmonar Primaria Familiar , Estudios Retrospectivos , Pronóstico
14.
Orthop Surg ; 16(4): 811-820, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38439564

RESUMEN

Fracture healing is a complex staged repair process in which the mechanical environment plays a key role. Bone tissue is very sensitive to mechanical stress stimuli, and the literature suggests that appropriate stress can promote fracture healing by altering cellular function. However, fracture healing is a coupled process involving multiple cell types that balance and limit each other to ensure proper fracture healing. The main cells that function during different stages of fracture healing are different, and the types and molecular mechanisms of stress required are also different. Most previous studies have used a single mechanical stimulus on individual mechanosensitive cells, and there is no relatively uniform standard for the size and frequency of the mechanical stress. Analyzing the mechanisms underlying the effects of mechanical stimulation on the metabolic regulation of signaling pathways in cells such as in bone marrow mesenchymal stem cells (BMSCs), osteoblasts, chondrocytes, and osteoclasts is currently a challenging research hotspot. Grasping how stress affects the function of different cells at the molecular biology level can contribute to the refined management of fracture healing. Therefore, in this review, we summarize the relevant literature and describe the effects of mechanical stress on cells associated with fracture healing, and their possible signaling pathways, for the treatment of fractures and the further development of regenerative medicine.


Asunto(s)
Curación de Fractura , Fracturas Óseas , Humanos , Estrés Mecánico , Huesos , Osteoclastos
15.
Int J Biol Macromol ; 266(Pt 1): 130982, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38522693

RESUMEN

This work aimed to propose a rapid method to screen the bioactive peptides with anti-α-glucosidase activity instead of traditional multiple laborious purification and identification procedures. 242 peptides binding to α-glycosidase were quickly screened and identified by bio-affinity ultrafiltration combined with LC-MS/MS from the double enzymatic hydrolysate of black beans. Top three peptides with notable anti-α-glucosidase activity, NNNPFKF, RADLPGVK and FLKEAFGV were further rapidly screened and ranked by the three artificial intelligence tools (three-AI-tool) BIOPEP database, PeptideRanker and molecular docking from the 242 peptides. Their IC50 values were in order as 4.20 ± 0.11 mg/mL, 2.83 ± 0.03 mg/mL, 1.32 ± 0.09 mg/mL, which was opposite to AI ranking, for the hydrophobicity index of the peptides was not included in the screening criteria. According to the kinetics, FT-IR, CD and ITC analyses, the binding of the three peptides to α-glucosidase is a spontaneous and irreversible endothermic reaction that results from hydrogen bonds and hydrophobic interactions, which mainly changes the α-helix structure of α-glucosidase. The peptide-activity can be evaluated vividly by AFM in vitro. In vivo, the screened FLKEAFGV and RADLPGVK can lower blood sugar levels as effectively as acarbose, they are expected to be an alternative to synthetic drugs for the treatment of Type 2 diabetes.


Asunto(s)
Inhibidores de Glicósido Hidrolasas , Simulación del Acoplamiento Molecular , Péptidos , Espectrometría de Masas en Tándem , alfa-Glucosidasas , Inhibidores de Glicósido Hidrolasas/farmacología , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/aislamiento & purificación , Péptidos/química , Péptidos/farmacología , alfa-Glucosidasas/química , alfa-Glucosidasas/metabolismo , Cromatografía Liquida/métodos , Cinética , Ultrafiltración/métodos , Fabaceae/química , Cromatografía Líquida con Espectrometría de Masas
16.
Food Chem X ; 21: 101199, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38495028

RESUMEN

A reliable and sensitive UPLC-MS/MS method coupled with HLB-SPE was developed for simultaneous determination of T-2 and its modified forms (HT-2, NEO, T-2-triol, T-2-tetraol, T-2-3G, and HT-2-3G) in cereals and cereal-based products. Acceptable linearity (R2 ≥ 0.99), limits of quantitation (0.5-10.0 µg/kg), intra-day precision (RSD < 12.8 %), inter-day precision (RSD ≤ 15.8 %), and recovery (76.8 %-115.2 %) were obtained for all analytes in all matrices investigated. 107 commercial foodstuffs were analyzed, and T-2 was detected in 29.0 % of maize and maize flour samples (0.51 to 56.61 µg/kg) and in 10-33.3 % of wheat flour and barley samples (1.27 to 78.51 µg/kg). Moreover, 66.7 % of the positive samples were simultaneously contaminated with two or more T-2 forms. The possible health risk related to T-2 and its modified forms in cereals and cereal-based products was evaluated using a probabilistic dietary exposure assessment. The 95th percentile dietary exposure values of the sum of T-2 forms ranged from 0.16 to 1.70 ng/kg b.w./day for lower bound (LB), and 0.17 to 7.59 ng/kg b.w./day for upper bound (UB). Results strongly suggested that the presence of T-2 and its modified forms in cereals and cereal-based products warrants greater attention and investigation, although probabilistic dietary exposure values currently remain below the tolerable daily intake (TDI) value of 20 ng/kg b.w./day.

17.
Food Chem X ; 22: 101289, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38544933

RESUMEN

Oligosaccharides are low-molecular-weight carbohydrates between monosaccharides and polysaccharides. They can be extracted directly from natural products by physicochemical methods or obtained by chemical synthesis or enzymatic reaction. Oligosaccharides have important physicochemical and physiological properties. Their research and production involve many disciplines such as medicine, chemical industry, and biology. Functional oligosaccharides, as an excellent functional food base, can be used as dietary fibrer and prebiotics to enrich the diet; improve the microecology of the gut; exert antitumour, anti-inflammatory, antioxidant, and lipid-lowering properties. Therefore, the industrial applications of oligosaccharides have increased rapidly in the past few years. It has great prospects in the field of food and medicinal chemistry. This review summarized the preparation, structural features and biological activities of oligosaccharides, with particular emphasis on the application of functional oligosaccharides in the food industry and human nutritional health. It aims to inform further research and development of oligosaccharides and food chemistry.

18.
Medicine (Baltimore) ; 103(5): e37095, 2024 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-38306541

RESUMEN

Ulcerative colitis (UC) has seen a significant increase over the past 3 decades. However, our understanding of its etiology, pathogenesis, and pharmacological treatment remains limited. This comprehensive review aims to address these gaps by analyzing trends, evaluating previous research, and providing insights for future investigations. We conducted a bibliometric analysis of UC-related papers indexed in the Web of Science from 1993 to 2022. The author, organization, country, and keyword networks in the field of UC were visualized. A total of 36,483 papers were included, showing a continuous upward trend. Most research on UC was conducted in universities, with hospitals leading in high-quality studies. The United States emerged as the primary contributor, followed by China and the United Kingdom. The overall quality of UC-related publications improved, indicating sustained interest in the field. The keywords related to UC was classified into 9 clusters. Keywords detection revealed that UC research focused mainly on the discovery of its etiology and exploration of treatment methods, with research directions evolving from initial treatment of UC and related diseases to clinical trials of UC and subsequently incorporating genomics and bioinformatics techniques to study UC and explore new therapeutic methods and drugs, including recent advances in gut microbiota. Our study identified gaps in understanding the etiology, pathogenesis, and treatment of UC. Future research in UC should focus on genomics, personalized treatment, microbial therapy and leveraging machine learning and artificial intelligence. These areas hold the potential for improving UC diagnosis, treatment, and management.


Asunto(s)
Inteligencia Artificial , Colitis Ulcerosa , Humanos , Colitis Ulcerosa/epidemiología , Colitis Ulcerosa/terapia , Bibliometría , China , Biología Computacional
19.
Int J Mol Sci ; 25(4)2024 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-38397050

RESUMEN

Complement component 4 binding protein α (C4BPA) is an immune gene which is responsible for the complement regulation function of C4BP by binding and inactivating the Complement component C4b (C4b) component of the classical Complement 3 (C3) invertase pathway. Our previous findings revealed that C4BPA was differentially expressed by comparing the transcriptome in high-fat and low-fat bovine mammary epithelial cell lines (BMECs) from Chinese Holstein dairy cows. In this study, a C4BPA gene knockout BMECs line model was constructed via using a CRISPR/Cas9 system to investigate the function of C4BPA in lipid metabolism. The results showed that levels of triglyceride (TG) were increased, while levels of cholesterol (CHOL) and free fatty acid (FFA) were decreased (p < 0.05) after knocking out C4BPA in BMECs. Additionally, most kinds of fatty acids were found to be mainly enriched in the pathway of the biosynthesis of unsaturated fatty acids, linoleic acid metabolism, fatty acid biosynthesis, and regulation of lipolysis in adipocyte. Meanwhile, the RNA-seq showed that most of the differentially expressed genes (DEGs) are related to PI3K-Akt signaling pathway. The expressions of 3-Hydroxy-3-Methylglutaryl-CoA Synthase 1 (HMGCS1), Carnitine Palmitoyltransferase 1A (CPT1A), Fatty Acid Desaturase 1 (FADS1), and Stearoyl-Coenzyme A desaturase 1 (SCD1) significantly changed when the C4BPA gene was knocked out. Collectively, C4BPA gene, which is an immune gene, played an important role in lipid metabolism in BMECs. These findings provide a new avenue for animal breeders: this gene, with multiple functions, should be reasonably utilized.


Asunto(s)
Complemento C4 , Metabolismo de los Lípidos , Fosfatidilinositol 3-Quinasas , Animales , Bovinos , Femenino , Complemento C4/metabolismo , Células Epiteliales/metabolismo , Ácidos Grasos/metabolismo , Metabolismo de los Lípidos/genética , Glándulas Mamarias Animales/metabolismo , Leche/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Transcriptoma
20.
Ther Adv Respir Dis ; 18: 17534666241232521, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38409856

RESUMEN

BACKGROUND: Balloon pulmonary angioplasty (BPA) is typically performed in a sequential manner. OBJECTIVES: This study aimed to determine the lowest frequency of BPA for patients who could not reach treatment goals in a short period. DESIGN: Retrospective cohort. METHODS: We retrospectively enrolled 186 BPA-treated patients diagnosed with chronic thromboembolic pulmonary hypertension. According to the accumulative number of performed BPA sessions or treated pulmonary vessels or the ratio of the number of treated pulmonary vessels/the number of baseline lesions (T/P) prior to the initial occurrence of clinical outcome or censored date, we divided patients into different groups. The principal outcome was clinical worsening. RESULTS: After stratifying patients by the number of performed BPA sessions, most baseline parameters were comparable among groups. During follow-up, 31 (16.7%) of 186 patients experienced clinical worsening. The 6-month cumulative clinical worsening-free survival rates of ⩾2 performed sessions group were significantly higher than that of 1 performed session group. The 12-month cumulative rates of clinical worsening-free survival exhibited a declining pattern in the subsequent sequence: ⩾3, 2, and 1 performed BPA sessions, and this trend persisted when follow-up time exceeded 12 months. The 6-, 12-, and 24-month cumulative clinical worsening-free survival rates were comparable between patients with 3 and ⩾4 performed BPA sessions. Similar results were also observed when stratifying patients by the accumulative number of treated pulmonary vessels (⩽8, 9-16, ⩾17) and T/P (⩽0.789, 0.790-1.263, ⩾1.264). CONCLUSION: To achieve optimal short-term outcomes, patients might need to undergo ⩾2 BPA sessions or have ⩾9 pulmonary vessels treated or have T/P ⩾0.790 within 6 months, and undergo ⩾3 BPA sessions or have ⩾17 pulmonary vessels treated or have T/P ⩾1.264 within 12 months.


The least number of BPA session to reach a favorable outcomeWhy was the study done? Balloon pulmonary angioplasty (BPA) has been recommended for patients with chronic thromboembolic pulmonary hypertension, which can significantly improve patients' hemodynamics. However, BPA is typically performed in a stepwise manner, and the duration from the initial session to the final session could extend over a year. If patients could not quickly undergo adequate number of BPA sessions and reach hemodynamic target due to various reasons, what is the best frequency of BPA for them? What did the researchers do? We retrospectively enrolled 186 BPA-treated patients diagnosed with chronic thromboembolic pulmonary hypertension. According to the accumulative number of BPA sessions, we divided patients into different groups to identify the best frequency of BPA to improve prognosis. What did the researchers find? Patients who received at least two BPA sessions within six months had significantly better prognosis than those with one BPA session. Patients who received at least three BPA sessions within a year had significantly better prognosis than those with two BPA sessions. What do the findings mean? To achieve optimal short-term outcome, patients might need to undergo at least two BPA sessions within six months, and undergo at least three BPA sessions within a year.


Asunto(s)
Angioplastia de Balón , Embolia Pulmonar , Humanos , Arteria Pulmonar , Estudios Retrospectivos , Enfermedad Crónica , Angioplastia de Balón/efectos adversos , Angioplastia de Balón/métodos , Resultado del Tratamiento
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