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Leaf flattening plays a pivotal role in optimizing light capture and enhancing photosynthesis efficiency. While extensive research has clarified the molecular mechanisms governing the initial stages of leaf flattening, understanding the maintenance of this process in mature leaves remains limited. Our investigation focused on sly-miR398b in tomatoes and revealed its crucial role in maintaining leaf flattening. In situ hybridization experiments indicated predominant expression of sly-miR398b in the abaxial side. Disrupting sly-miR398b using CRISPR/Cas9 relieved its suppression on target gene (Cu/Zn-SOD, SlCSD1), elevating SlCSD1 levels specifically on the abaxial side. Consequently, this asymmetrical expression of SlCSD1 increased hydrogen peroxide (H2O2) levels in the abaxial side, hindering auxin influx genes while promoting auxin efflux gene expression. This shift reduced auxin response gene expression in the abaxial side of mature leaves compared to the adaxial side, leading to leaf epinasty in sly-miR398b mutants. Exogenous H2O2 spraying induced leaf epinasty, downregulating SlGH3.5 and upregulating SlPIN3 and SlPIN4. Remarkably, spraying with 1-naphthalacetic acid (NAA) restored leaf flattening in sly-miR398b mutants. Our findings offer novel insights into mature leaf flattening maintenance via sly-miR398b's regulation of auxin and H2O2 signalling pathways.
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Efficient and safe extraction of microRNAs (miRNAs) from biological samples is pivotal for genetic regulation studies and biotechnological applications. This study focuses on optimizing the microRNA extraction process from the plasma of common carp, a significant species in aquaculture. Recognizing the limitations and hazards of commercial extraction kits, which often employ toxic chemicals like phenol and chloroform, we sought to develop a safer and more effective alternative. Our optimized protocol utilizes guanidinium isothiocyanate (GITC) and sarkosyl, omitting hazardous substances. We explored several parameters including GITC concentration, the addition of sarkosyl, and the role of sodium chloride in enhancing miRNA yield. Our findings demonstrate that optimal conditions involve a GITC concentration of 4.2 M, a 3% sarkosyl concentration, and the use of sodium chloride at 0.5 M. We also investigated the utility of glycogen as a nucleic acid carrier, finding 160 µg to be the optimal concentration. Comparative analysis with commercial kits indicated our method provides higher miRNA yields with reduced cycle threshold values, underscoring the effectiveness of our custom protocol. This optimized approach not only enhances miRNA recovery but also emphasizes safety and cost-effectiveness, making it a valuable method for both research and practical applications in aquaculture.
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PURPOSE: This study aims to assess the diagnostic efficacy of Korean Thyroid imaging reporting and data system (K-TIRADS), S-Detect software and contrast-enhanced ultrasound (CEUS) when employed individually, as well as their combined application, for the evaluation of thyroid nodules, with the objective of identifying the optimal method for diagnosing thyroid nodules. METHODS: Two hundred and sixty eight cases pathologically proven of thyroid nodules were retrospectively enrolled. Each nodule was classified according to K-TIRADS. S-Detect software was utilized for intelligent analysis. CEUS was employed to acquire contrast-enhanced features. RESULTS: The area under curve (AUC) values for diagnosing benign and malignant thyroid nodules using K-TIRADS alone, S-Detect software alone, CEUS alone, the combined application of K-TIRADS and CEUS, the combined application of S-Detect software and CEUS were 0.668, 0.668, 0.719, 0.741, and 0.759, respectively (p < 0.001). The sensitivity rate of S-Detect software was 89.9% (p < 0.001). It was the highest of the five diagnostic methods above. CONCLUSION: The utilization of S-Detect software can be served as a powerful tool for early screening. Notably, the combined utilization of S-Detect software with CEUS demonstrates superior diagnostic performance compared to employing K-TIRADS, S-Detect software, CEUS used individually, as well as the combined application of K-TIRADS with CEUS.
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Metabolic dysfunction-associated diseases often refer to various diseases caused by metabolic problems such as glucose and lipid metabolism disorders. With the improvement of living standards, the increasing prevalence of metabolic diseases has become a severe public health problem, including metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-related liver disease (ALD), diabetes and obesity. These diseases are both independent and interdependent, with complex and diverse molecular mechanisms. Therefore, it is urgent to explore the molecular mechanisms and find effective therapeutic targets of these diseases. MicroRNAs (miRNAs) have emerged as key regulators of metabolic homoeostasis due to their multitargets and network regulatory properties within the past few decades. In this review, we discussed the latest progress in the roles of miRNA-mediated regulatory networks in the development and progression of MASLD, ALD, diabetes and obesity.
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Enfermedades Metabólicas , MicroARNs , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Animales , Enfermedades Metabólicas/metabolismo , Enfermedades Metabólicas/terapia , Enfermedades Metabólicas/genética , Obesidad/metabolismo , Obesidad/genética , Diabetes Mellitus/metabolismo , Diabetes Mellitus/genética , Diabetes Mellitus/terapia , Hígado Graso/metabolismo , Hígado Graso/genética , Hígado Graso/terapia , Hígado Graso/etiologíaRESUMEN
Immune checkpoint inhibitors have shown remarkable benefits in the treatment of solid tumors,while the occurrence of atypical response patterns and immune-related adverse events during treatment challenges the accuracy of therapeutic evaluation.Medical imaging is crucial for the evaluation of immunotherapy.It enables the assessment of treatment efficacy via both morphological and functional ways and offers unique a predictive value when being combined with artificial intelligence.Here we review the recent research progress in imaging-based evaluation of solid tumors treated with immune checkpoint inhibitors.
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Inhibidores de Puntos de Control Inmunológico , Inmunoterapia , Neoplasias , Humanos , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inmunoterapia/métodos , Inteligencia ArtificialRESUMEN
Alzheimer's disease (AD) has been conceptualized as a syndrome of brain network dysfunction. Recent imaging connectomics studies have provided unprecedented opportunities to map structural and functional brain networks in AD. By reviewing molecular, imaging, and computational modeling studies, we have shown that highly connected brain hubs are primarily distributed in the medial and lateral prefrontal, parietal, and temporal regions in healthy individuals and that the hubs are selectively and severely affected in AD as manifested by increased amyloid-beta deposition and regional atrophy, hypo-metabolism, and connectivity dysfunction. Furthermore, AD-related hub degeneration depends on the imaging modality with the most notable degeneration in the medial temporal hubs for morphological covariance networks, the prefrontal hubs for structural white matter networks, and in the medial parietal hubs for functional networks. Finally, the AD-related hub degeneration shows metabolic, molecular, and genetic correlates. Collectively, we conclude that the brain-network-hub-degeneration framework is promising to elucidate the biological mechanisms of network dysfunction in AD, which provides valuable information on potential diagnostic biomarkers and promising therapeutic targets for the disease.
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BACKGROUND: Percutaneous coronary intervention (PCI) can provide benefits for anatomically suitable left main coronary artery (LMCA) lesions. When compared to traditional coronary angiography (CAG) -guided PCI, the use of intravascular ultrasound (IVUS) guidance has shown significant long-term prognostic improvements in LMCA PCI. Optical coherence tomography (OCT) offers a higher axial resolution than IVUS. However, there is currently a lack of relevant randomized controlled trials investigating the use of OCT specifically for left main distal bifurcation lesions. METHODS: The ISOLEDS trial is an ongoing multicenter study that aims to compare IVUS-guided PCI with OCT-guided PCI for patients with true LMCA distal bifurcation lesions. This prospective, randomized, controlled, non-inferiority trial will enroll a total of 664 patients with visually-defined Medina 1,1,1 or 0,1,1 classification of left main distal bifurcation lesions. The patients will be randomly assigned in a 1:1 ratio to either IVUS-guided or OCT-guided PCI. The primary endpoint is to assess the occurrence of target lesion failure (TLF) within 12â¯months after the procedure. After undergoing PCI, patients are required to visit the hospital for a 12-month clinical follow-up. During this clinical assessment, CAG can be performed to evaluate the status of target lesions. DISCUSSION: The ISOLEDS trial represents the first attempt to compare two distinct intracoronary imaging techniques for guiding PCI in patients with true LMCA distal bifurcation lesions. By evaluating and comparing the outcomes of these two imaging techniques, the trial results will aid operators in selection of the most effective approach for guiding PCI in these patients.
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Changes in plant morphology due to mechanical stimulation are known as thigmo responses. As climbing organs in plants, tendrils can sense mechanical stimulation after attaching to a support and then change their morphology within a short time. Here, the thigmo responses of cucumber tendril were investigated. Our results showed that mechanical stimulation stopped tendril elongation and that tendril length was determined by the distance from the support in cucumber. The mimicry touch treatment indicated that mechanical stimulation stopped tendril elongation by inhibiting cell expansion. RNA-seq data showed that three gibberellin (GA) metabolic genes (CsGA2ox3, CsCYP714A2, and CsCYP714A3) were upregulated in mechanically stimulated tendrils, and a major endogenous bio-active GA (GA4) was reduced in mechanically stimulated tendrils. The roles of CsGA2ox3, CsCYP714A2, and CsCYP714A3 in GA deactivation were confirmed by their overexpression in transgenic Arabidopsis. Moreover, exogenous GA treatment recovered tendril elongation under mechanical stimulation, whereas exogenous uniconazole treatment inhibited tendril elongation without mechanical stimulation, suggesting that mechanical stimulation stopped tendril elongation, depending on GA deactivation. In summary, our results suggest that GA deactivation plays an important role in tendril thigmo response, ensuring that tendrils obtain a suitable final length according to their distance from the support in cucumber.
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BACKGROUND: High-density lipoprotein cholesterol (HDL-C) is widely recognized for its protective effects against cognitive decline. However, recent studies have presented conflicting results, with some suggesting no significant cognitive benefits or even an increased risk of dementia associated with high HDL-C levels. For those who suffer from depression, the cognitive benefits of HDL-C may be diminished or reversed. The purpose of this study is to investigate the associations between HDL-C, cognitive ability, and depressive symptoms in middle-aged and older Chinese adults. METHODS: The datasets utilized were sourced from the China Health and Retirement Longitudinal Study (CHARLS) for the years 2011 and 2015, comprising 4,302 participants. Cross-lagged models were employed to explore the temporal sequence between cognitive performance and HDL-C levels, and to examine the interplay among depression, cognition, and HDL-C. Confounding factors such as sociodemographic characteristics, sleep conditions, and history of chronic diseases were controlled for. RESULTS: The analysis revealed unidirectional effects of baseline impaired cognition and greater severity of depression on increased HDL-C levels at follow-up (ß = - 0.036 and ß = 0.028, respectively, P < 0.05). However, higher baseline HDL-C levels did not significantly predict cognitive performance or depression 4 years later (ß = - 0.008 and ß = 0.023, respectively, P > 0.05). Depressive symptoms and cognition were found to have a significant bidirectional association (ß = - 0.026 and ß = - 0.053, respectively, P < 0.05). CONCLUSIONS: Cognitive impairment and depression are associated with higher HDL-C levels, whereas higher HDL-C levels do not appear to protect against cognitive decline or depressive symptoms. These findings underscore the importance of preserving cognitive and mental health, which may lower the likelihood of cardiovascular disease and dementia. Future studies should validate these findings and develop targeted interventions tailored to specific populations.
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HDL-Colesterol , Disfunción Cognitiva , Depresión , Humanos , HDL-Colesterol/sangre , Disfunción Cognitiva/sangre , Femenino , Masculino , Persona de Mediana Edad , Depresión/sangre , Depresión/epidemiología , Anciano , China/epidemiología , Estudios Longitudinales , Factores de Riesgo , Cognición , Pueblos del Este de AsiaRESUMEN
INTRODUCTION: Mechanical stresses incurred during post-harvest fruit storage and transportation profoundly impact decay and losses. Currently, the monitoring of mechanical forces is primarily focused on vibrational forces experienced by containers and vehicles and impact forces affecting containers. However, the detection of compressive forces both among interior fruit and between fruit and packaging surfaces remains deficient. Hence, conformable materials capable of sensing compressive stresses are necessary. OBJECTIVES: In the present study, a triple-network-reinforced PSA/LiCl/CCN@AgNP conductive hydrogel was synthesized for compression force detection on fruit surfaces based on changes in intrinsic impedance under mechanical loading. METHODS: The conductive hydrogel was characterized in terms of its adhesion, mechanics, frost resistance, water retention, conductivity, mechanical force-sensing properties, and feasibility for monitoring mechanical forces. Then, a portable complex impedance recorder was developed to interface with the conductive hydrogel and its mechanical force sensing ability was evaluated. RESULTS: Beyond its inherent conductivity, the hydrogel exhibited notable pressure sensitivity within the strain range of 1 % to 80 %. The conductive hydrogel also demonstrated a commendable adhesion property, favorable tensile property (580 % elongation at break), substantial compressive strength and durability, and a long-term water retention capability. After exposure to -20 °C for 96 h, the hydrogel maintained its mechanical strength, affirming its anti-freezing property. In addition, a portable complex impedance recorder with sustained signal measurement stability was developed to quantitatively acquire the hydrogel resistance changes in response to compression forces. Finally, the effectiveness of the conductive hydrogel for sensing compression force on the surface of apple fruits was validated. CONCLUSION: The conductive hydrogel holds promise for applications in smart packaging, wherein it can detect crucial mechanical stress on fruit, convert it into electrical signals, and further transmit these signals to the cloud, thereby enabling the real-time sensing of mechanical forces experienced by fruits and enhancing post-harvest fruit loss management.
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AIMS: To assess the validity and internal reliability of the International Trauma Questionnaire (ITQ) among patients diagnosed with major depressive disorder (MDD) and to explore the network structure of Complex post-traumatic stress disorder (CPTSD) among MDD patients in China. METHODS: Eligible individuals were recruited from a large tertiary hospital in Guangdong Province. Trained researchers conducted in-person interviews and administered self-report questionnaires, including demographics, medical information, and psychological assessments. Confirmatory factor analyses (CFA) and network analysis were performed, with calculations of Average Variance Extracted (AVE), Cronbach's α, and composite reliability. RESULTS: A total of 113 patients with MDD participated in this study. The correlated six-factor one-order model was a good representation of the latent structure of ITQ (χ2= 60.114, df = 39, P = 0.017, SRMR = 0.070, RMSEA = 0.050, TLI = 0.952, CFI = 0.972, BIC = 175.508). All ITQ subscales possessed acceptable convergent validity and internal reliability, except for affective dysregulation and re-experiencing. The square root of AVE for affective dysregulation was lower than its correlations with other clusters. Network analysis revealed that node C4 ('I feel worthless'), as a core symptom, was significantly associated with the development of CPTSD. CONCLUSIONS: The clinical applicability of the ITQ was demonstrated by its overall validity and reliability among patients with MDD. However, the affective dysregulation and re-experiencing clusters still need to be revised and enhanced. Timely screening, recognition, and diagnosis are critical due to the worse clinical outcomes seen in comorbid patients.
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Trastorno Depresivo Mayor , Psicometría , Trastornos por Estrés Postraumático , Humanos , Masculino , Femenino , Adulto , Trastornos por Estrés Postraumático/diagnóstico , Trastorno Depresivo Mayor/diagnóstico , Psicometría/normas , Psicometría/instrumentación , Persona de Mediana Edad , China , Reproducibilidad de los Resultados , Adulto Joven , Escalas de Valoración Psiquiátrica/normas , Encuestas y Cuestionarios/normas , Análisis Factorial , Pueblos del Este de AsiaRESUMEN
Plasma levels of oncofetal chondroitin sulfate (ofCS)-modified CD44 have emerged as a promising biomarker for multi-cancer detection. Here, we explored its potential to predict the survival of patients with lung cancer. A prospective observational cohort was conducted involving 274 newly diagnosed patients with lung cancer at the Sun Yat-sen University Cancer Center from 2013 to 2015. The plasma levels of ofCS-modified CD44 were measured, and Cox regression analysis was performed to assess the association between plasma-modified CD44 levels and overall survival (OS) as well as other prognostic outcomes. Prognostic nomograms were constructed based on plasma ofCS-modified CD44 levels to predict survival outcomes for patients with lung cancer. Patients with high expression ofCS-modified CD44 exhibited significantly worse outcomes in terms of OS (HR = 1.61, 95%CI = 1.13-2.29, p = 0.009) and progression-free survival (PFS). These findings were consistent across various analyses. The concordance index of the prognostic nomogram for predicting OS in both the training set and validation set were 0.723 and 0.737, respectively. Additionally, time-dependent receiver operating characteristic (ROC) curves showed that the nomogram could serve as a useful tool for predicting OS in patients with lung cancer. Plasma ofCS-modified CD44 may serve as an independent prognosis marker for patients with lung cancer. Further validation of its predictive value could enhance prognostic assessment and guide personalized treatment strategies for patients with lung cancer.
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Recent studies have identified microvascular invasion (MVI) as the most vital independent biomarker associated with early tumor recurrence. With advancements in medical technology, several computational methods have been developed to predict preoperative MVI using diverse medical images. These existing methods rely on human experience, attribute selection or clinical trial testing, which is often time-consuming and labor-intensive. Leveraging the advantages of deep learning, this study presents a novel end-to-end algorithm for predicting MVI prior to surgery. We devised a series of data preprocessing strategies to fully extract multi-view features from the data while preserving peritumoral information. Notably, a new multi-branch deep fused feature algorithm based on ResNet (DFFResNet) is introduced, which combines Magnetic Resonance Images (MRI) from different sequences to enhance information complementarity and integration. We conducted prediction experiments on a dataset from the Radiology Department of the First Hospital of Lanzhou University, comprising 117 individuals and seven MRI sequences. The model was trained on 80% of the data using 10-fold cross-validation, and the remaining 20% were used for testing. This evaluation was processed in two cases: CROI, containing samples with a complete region of interest (ROI), and PROI, containing samples with a partial ROI region. The robustness results from repeated experiments at both image and patient levels demonstrate the superior performance and improved generalization of the proposed method compared to alternative models. Our approach yields highly competitive prediction results even when the ROI region outline is incomplete, offering a novel and effective multi-sequence fused strategy for predicting preoperative MVI.
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Objective: Sarcopenia is a gradually advancing systemic disorder affecting skeletal muscles, primarily distinguished by diminished muscle mass and functional decline. As of present, a universally accepted diagnostic criterion for sarcopenia has yet to be established. From the perspective of the constitution theory in traditional Chinese medicine (TCM), the Yin-deficiency constitution is believed to have a significant correlation with the development of sarcopenia. The primary objective of this study was to examine the potential association between sarcopenia and Yin-deficiency constitution. Methods: The present study is a cross-sectional analysis. The Asian Working Group for Sarcopenia (AWGS) recommended a diagnostic criterion for sarcopenia. A total of 141 participants over 50 years of age were diagnosed with sarcopenia. To determine the constitution of each patient, classification and determination standards were used in traditional Chinese medicine. In this study, a combination of logistic regression and propensity score matching (PSM) was employed to analyze a dataset comprising 1,372 eligible observations. The diagnostic efficacy of the test in distinguishing sarcopenia was assessed through receiver operating characteristic (ROC) curve analysis. Results: The relationship between Yin-deficiency constitution and sarcopenia was examined using logistic regression analysis. In the crude model, the odds ratio (OR) was found to be 3.20 (95% confidence interval [CI]: 1.70-6.03). After adjusting for various confounding factors, including gender, sex, 6 m walking test/(m/s), SMI, and maximum grip strength/kg, the OR increased to 9.70 (95% CI: 3.20-69.38). The associations between seven other biased traditional Chinese medicine (TCM) constitutions and sarcopenia were not found to be statistically significant in the fully adjusted model. The propensity score matching (PSM) analysis yielded consistent results with the logistic regression analysis. Receiver operating characteristic (ROC) curve analysis showed that the AUC of the Yin-deficiency constitution combined with age and gender reached 0.707. Conclusion: Among the nine TCM constitutions examined, the Yin-deficiency constitution demonstrates an independent association with sarcopenia. Yin-deficiency constitution may serve as a potential risk factor for the development of sarcopenia. To establish a causal relationship, further experimental investigations are warranted. The diagnostic performance of sarcopenia is effectively demonstrated by the Yin-deficiency constitution combined with age and gender.
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Medicina Tradicional China , Sarcopenia , Humanos , Sarcopenia/diagnóstico , Estudios Transversales , Femenino , Masculino , Anciano , Persona de Mediana Edad , Deficiencia Yin/diagnóstico , Curva ROC , Anciano de 80 o más AñosRESUMEN
The minimally invasive injection of tissue engineering scaffolds is of interest as it requires a smaller incision and quickens recovery. However, the engineering of scaffolds capable of injection remains a challenge. Here, we report on a shrunken scaffold inspired by the shrinking of puffed food in a humid environment. A scaffold is freeze-dried to remove water then placed in a humid atmosphere. The humidity causes the dry scaffold to shrink by up to 90%. In addition, the humidity treatment reduces the scaffolds modulus minimizing the foreign body response after implantation. The scaffolds can rapidly swell into their original size and shape after application. A tool for the delivery of the minimally invasive scaffolds is developed and we demonstrate the potential for minimally invasive delivery using this shrinking technique.
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Ingeniería de Tejidos , Andamios del Tejido , Andamios del Tejido/química , Ingeniería de Tejidos/métodos , Animales , Humedad , Liofilización/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Ratones , Materiales Biocompatibles/químicaRESUMEN
Introduction: Fibroblast activation protein (FAP) overexpression on cancer-associated fibroblasts (CAFs) is associated with poor prognosis and worse clinical outcomes. Selective ablation of pro-tumorgenic FAP+ stromal cells with CAR-T cells may be a new therapeutic strategy. However, the clinical use of FAP-CAR T cells is suggested to proceed with caution for occasional poor efficacy and induction of on-target off-tumor toxicity (OTOT), including lethal osteotoxicity and cachexia. Hence, more investigations and preclinical trials are required to optimize the FAP-CAR T cells and to approve their safety and efficacy. Methods: In this study, we designed second-generation CAR T cells targeting FAP with 4-1BB as a co-stimulatory molecule, and tested their cytotoxicity against FAP-positive cells (hFAP-HT1080 cells and a variety of primary CAFs) in vitro and in Cell line-derived xenograft (CDX) and a patient-derived xenograft (PDX) model. Results: Results showed that our FAP-CAR T cells were powerfully potent in killing human and murine FAP-positive tumor cells and CAFs in multiple types of tumors in BALB/c and C57BL/6 mice and in patient-derived xenografts (PDX) model. And they were proved to be biologically safe and exhibit low-level OTOT. Discussion: Taken together, the human/murine cross-reactive FAP-CAR T cells were powerfully potent in killing human and murine FAP positive tumor cells and CAFs. They were biologically safe and exhibit low-level OTOT, warranting further clinical investigation into our FAP-CAR T cells.
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Inmunoterapia Adoptiva , Receptores Quiméricos de Antígenos , Animales , Femenino , Humanos , Ratones , Fibroblastos Asociados al Cáncer/inmunología , Fibroblastos Asociados al Cáncer/metabolismo , Línea Celular Tumoral , Reacciones Cruzadas/inmunología , Endopeptidasas , Gelatinasas/inmunología , Gelatinasas/metabolismo , Inmunoterapia Adoptiva/métodos , Inmunoterapia Adoptiva/efectos adversos , Proteínas de la Membrana/inmunología , Proteínas de la Membrana/genética , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Neoplasias/inmunología , Neoplasias/terapia , Receptores Quiméricos de Antígenos/inmunología , Receptores Quiméricos de Antígenos/genética , Serina Endopeptidasas/inmunología , Serina Endopeptidasas/genética , Serina Endopeptidasas/metabolismo , Linfocitos T/inmunología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Segmental bone defects and nonunion of fractures caused by trauma, infection, tumor or systemic diseases with limited osteogenesis and prolonged bone healing cycles are challenging issues in orthopedic clinical practice. Therefore, identifying regulatory factors for bone tissue regeneration and metabolism is crucial for accelerating bone repair and reconstructing defective areas. Silence information regulator 6 (SIRT6), functioning as a deacetylase and nucleotide transferase, is extensively involved in the regulation of differentiation, apoptosis, metabolism, and inflammation in bone cells including osteoblasts and osteoclasts, and is considered to be an important factor in regulating bone metabolism. SIRT6 forms a complex with B lymphocyte-induced maturation protein 1 (Blimp1), down-regulates the expression of the nuclear factor κB (NF-κB) pathway, and promotes the expression of the ERα-FasL axis signal to inhibit osteoclast formation and maturation differentiation, thereby hindering bone resorption and increasing bone mass. In addition, SIRT6 activates the Akt-mTOR pathway to regulate the autophagy level and osteogenesis of bone marrow mesenchymal stem cells, inhibits glycolysis and reactive oxygen production in osteoblasts, promotes osteoblast differentiation through the CREB/CCN1/COX2 pathway and the bone morphogenetic protein (BMP) signaling pathway, enhances bone formation, and accelerates bone regeneration and repair of skeletal tissue. This article provides an overview of the research progress on SIRT6 in the pathophysiology of bone regeneration, revealing its potential as a novel therapeutic target for bone tissue repair to alleviate the progression of skeletal pathological diseases.
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Regeneración Ósea , Osteogénesis , Sirtuinas , Humanos , Sirtuinas/metabolismo , Osteoblastos , Animales , Diferenciación Celular , Transducción de Señal , Osteoclastos , FN-kappa B/metabolismoRESUMEN
Serious adverse drug reactions of gentamicin (GM) significantly limit its clinical use, thus there is an urgent demand to develop reliable strategies to detect its concentration. In this study, we have developed a novel highly sensitive and portable lateral flow immunoassay (LFIA) based on CoFe PBAs/WS2 nanozyme mediated chemiluminescence (CL) and photothermal (PT) dual-mode POCT biosensor for the detection of GM, which successfully combines sensitive laboratory analyses with portable in situ analyses in the field. In this proof-of-principle work, the dynamic detection ranges of CL-LFIA and PT-LFIA mode were 1 pg mL-1 to 100 ng mL-1 and 50 pg mL-1 to 100 ng mL-1 with the limits of detection of 0.33 and 16.67 pg mL-1, respectively. The whole detection of CL-LFIA and PT-LFIA could be completed within 15 min and 30 min, respectively. The recoveries of GM spiked into complex matrices including milk, urine, and serum for CL-LFIA and PT-LFIA were 90.94%-109.74% and 94.49%-109.31%, respectively, indicating the reliability and applicability of the dual-mode LFIA in real samples. The dual-mode POCT biosensor could effectively overcome the false problems with improving accuracy and sensitivity, enabling user to precisely detect GM by laboratory analysis or on-site analysis depending on the source condition. Due to the complementary properties of CL-LFIA and PT-LFIA, the developed POCT biosensor can effectively ensure high-performance detection, showing the potential application of accurately detecting drug concentration in clinical practice.
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Técnicas Biosensibles , Gentamicinas , Límite de Detección , Mediciones Luminiscentes , Pruebas en el Punto de Atención , Gentamicinas/análisis , Gentamicinas/sangre , Técnicas Biosensibles/métodos , Inmunoensayo/métodos , Mediciones Luminiscentes/métodos , Humanos , Animales , Antibacterianos/análisis , Antibacterianos/sangre , Antibacterianos/orina , Leche/química , Cobalto/químicaRESUMEN
Identifying the aging time of Liupao Tea (LPT) presents a persistent challenge. We utilized an AI-Multimodal fusion method combining FTIR, E-nose, and E-tongue to discern LPT's aging years. Compared to single-source and two-source fusion methods, the three-source fusion significantly enhanced identifying accuracy across all four machine learning algorithms (Decision tree, Random forest, K-nearest neighbor, and Partial least squares Discriminant Analysis), achieving optimal accuracy of 98-100 %. Physicochemical analysis revealed monotonic variations in tea polysaccharide (TPS) conjugates with aging, observed through SEM imaging as a transition from lamellar to granular TPS conjugate structures. These quality changes were reflected in FTIR spectral characteristics. Two-dimensional correlation spectroscopy (2D-COS) identified sensitive wavelength regions of FTIR from LPT and TPS conjugates, indicating a high similarity in spectral changes between TPS conjugates and LPT with aging years, highlighting the significant role of TPS conjugates variation in LPT quality. Additionally, we established an index for evaluating quality of aging, which is sum of three fingerprint peaks (1029 cm-1, 1635 cm-1, 2920 cm-1) intensities. The index could effectively signify the changes in aging years on macro-scale (R2 = 0.94) and micro-scale (R2 = 0.88). These findings demonstrate FTIR's effectiveness in identifying aging time, providing robust evidence for quality assessment.
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Polisacáridos , Té , Té/química , Polisacáridos/química , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Aprendizaje Automático , Nariz ElectrónicaRESUMEN
Swine Enteric Coronaviruses (SECoVs), with high lethality and infectiousness, are the main pathogens causing fatal and watery diarrhea in piglets and spreading globally. Moreover, these SECoVs can cause similar clinical manifestations and are often co-infected, requiring an accurate assay suitable for rapid, in situ, and differential detection. Here, we developed a multiplexed fluorescent-based lateral flow immunoassay (mFB-LFIA) for the detection of three SECoVs, including porcine delta coronaviruses (PDCoV), transmissible gastroenteritis virus (TGEV), and porcine epidemic diarrhea virus (PEDV), in swine fecal samples. Thanks to the filter pad design and reasonable optimization, the mFB-LFIA was achieved within 15 min for three SECoVs detection simultaneously and improved the tolerance of the strips for feces samples. The limit of detection (LoD) of detecting PDCoV, TGEV, and PEDV were 2.1 × 104 TCID50 mL-1, 3.4 × 102 TCID50 mL-1, and 3.6 × 102 TCID50 mL-1, respectively. Additionally, the proposed assay was successfully applied to the detection of PDCoV, TGEV, and PEDV in swine feces with high accuracy. Compared with the gold standard nucleic acid testing, the total coincidence rate of the proposed assay was more than 90 %. Moreover, the mFB-LFIA performed excellent stability and repeatability. The proposed mFB-LFIA allows for rapid, in situ, more cost-effective and simultaneous detection of PDCoV, TGEV, and PEDV compared with nucleic acid testing. To the best of our knowledge, this is the first report to describe a multiplexed point-of-care assay capable of detecting PDCoV, TGEV, and PEDV in swine fecal samples. We believe our approach has a great potential for application to pig farm.