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RATIONALE AND OBJECTIVES: Deep learning can enhance the performance of multimodal image analysis, which is known for its noninvasive attributes and complementary efficacy, in predicting axillary lymph node (ALN) metastasis. Therefore, we established a multimodal deep learning model incorporating ultrasound (US) and magnetic resonance imaging (MRI) images to predict ALN metastasis in patients with breast cancer. MATERIALS AND METHODS: A retrospective cohort of patients with histologically confirmed breast cancer from two hospitals composed of the primary cohort (n = 465) and the external validation cohort (n = 123). All patients had undergone both preoperative US and MRI scans. After data preprocessing, three convolutional neural network models were used to analyze the US and MRI images, respectively. After integrating the US and MRI deep learning prediction results (DLUS and DLMRI, respectively), a multimodal deep learning (DLMRI+US+Clinical parameter) model was constructed. The predictive ability of the proposed model was compared to that of the DLUS, DLMRI, combined bimodal (DLMRI+US), and clinical parameter models. Evaluation was performed using the area under the receiver operating characteristic curves (AUCs) and decision curves. RESULTS: A total of 588 patients with breast cancer participated in this study. The DLMRI+US+Clinical parameter model outperformed the alternative models, achieving the highest AUCs of 0.819 (95% confidence interval [CI] 0.734-0.903) and 0.809 (95% CI 0.723-0.895) on the internal and external validation sets, respectively. The decision curve analysis confirmed its clinical usefulness. CONCLUSION: The DLMRI+USï¼Clinical parameter model demonstrates the feasibility and reliability of its performance for ALN metastasis prediction in patients with breast cancer.
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The microRNAs (miRNAs) of their hosts play an important role in regulating both the innate and adaptive immune responses to Cryptosporidium parvum infection. The mechanisms of autophagy and apoptosis are important components of the defense system against C. parvum infection. In this study, we investigate the role of miRNA-199a-3p in regulating MTOR-mediated autophagy and apoptosis in HCT-8 cells induced by C. parvum. The expression of miR-199a-3p increased at 3, 6 and 12 hours postinfection (hpi) but decreased at 24 and 48 hpi. The upregulation of miR-199a-3p promoted autophagy and apoptosis and limited the parasite burden in HCT-8 cells after C. parvum infection. The downregulation of miR-199a-3p inhibited the autophagy and apoptosis induced by C. parvum and enhanced the parasite burden in HCT-8 cells. A luciferase reporter showed that MTOR was a target gene of miR-199a-3p. Suppressed expression of MTOR by small interfering RNA (siRNA) promoted autophagy and apoptosis and limited C. parvum burden in HCT-8 cells. Co-transfection with miR-199a-3p inhibitor or si-mTOR revealed that miR-199a-3p regulates autophagy and apoptosis in HCT-8 cells through MTOR, to resist C. parvum infection. In conclusion, intestinal epithelial cells defend against C. parvum infection by regulating their autophagy and apoptosis through the miR-199a-3p-MTOR axis.
Subject(s)
Apoptosis , Autophagy , Cryptosporidiosis , Cryptosporidium parvum , MicroRNAs , TOR Serine-Threonine Kinases , MicroRNAs/genetics , MicroRNAs/metabolism , Humans , Autophagy/genetics , Apoptosis/genetics , Cryptosporidium parvum/genetics , TOR Serine-Threonine Kinases/metabolism , TOR Serine-Threonine Kinases/genetics , Cryptosporidiosis/parasitology , Cryptosporidiosis/genetics , Cell Line, TumorABSTRACT
Recent studies show that systemic administration of a glucagon-like peptide-1 receptor (GLP-1R) agonist is sufficient to attenuate the reinstatement of cocaine-seeking behavior, an animal model of relapse. However, the neural mechanisms mediating these effects and the role of endogenous central GLP-1 signaling in cocaine seeking remain unknown. Here, we show that voluntary cocaine taking decreased plasma GLP-1 levels in rats and that chemogenetic activation of GLP-1-producing neurons in the nucleus tractus solitarius (NTS) that project to the ventral tegmental area (VTA) decreased cocaine reinstatement. Single nuclei transcriptomics and FISH studies revealed GLP-1Rs are expressed primarily on GABA neurons in the VTA. Using in vivo fiber photometry, we found that the efficacy of a systemic GLP-1R agonist to attenuate cocaine seeking was associated with increased activity of VTA GABA neurons and decreased activity of VTA dopamine neurons. Together, these findings suggest that targeting central GLP-1 circuits may be an effective strategy toward reducing cocaine relapse and highlight a novel functional role of GABAergic GLP-1R-expressing midbrain neurons in drug seeking.
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Seawater electrolysis for the production of fuels and chemicals involved in onshore and offshore plants powered by renewable energies offers a promising avenue and unique advantages for energy and environmental sustainability. Nevertheless, seawater electrolysis presents long-term challenges and issues, such as complex composition, potential side reactions, deposition of and poisoning by microorganisms and metal ions, as well as corrosion, thus hindering the rapid development of seawater electrolysis technology. This review focuses on the production of value-added fuels (hydrogen and beyond) and fine chemicals through seawater electrolysis, as a promising step towards sustainable energy development and carbon neutrality. The principle of seawater electrolysis and related challenges are first introduced, and the redox reaction mechanisms of fuels and chemicals are summarized. Strategies for operating anodes and cathodes including the development and application of chloride- and impurity-resistant electrocatalysts/membranes are reviewed. We comprehensively summarize the production of fuels and chemicals (hydrogen, carbon monoxide, sulfur, ammonia, etc.) at the cathode and anode via seawater electrolysis, and propose other potential strategies for co-producing fine chemicals, even sophisticated and electronic chemicals. Seawater electrolysis can drive the oxidation and upgrading of industrial pollutants or natural organics into value-added chemicals or degrade them into harmless substances, which would be meaningful for environmental protection. Finally, the perspective and prospects are outlined to address the challenges and expand the application of seawater electrolysis.
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Purpose: With population aging, individuals in underdeveloped areas may experience a higher prevalence of chronic non-communicable diseases (NCDs), a lower level of health-related quality of life (HRQoL), and distinct lifestyles. However, this triadic association remains inadequately studied, particularly regarding the role of health lifestyle. This study aims to examine the relationship between the number of NCDs and HRQoL, while considering the moderating effect of health lifestyle among middle-aged and older adults residing in resource-limited areas. Methods: This cross-sectional study was conducted in Yunnan Province from July to December 2022. Participants completed a self-report questionnaire related to socio-demographic information, NCDs conditions, health lifestyle status, and HRQoL, which was assessed using the EuroQol five-dimension five-level (EQ-5D-5L) scale. Hierarchical regression and simple slope tests were used to examine the moderating effect of health lifestyle. Results: Out of the total 2704 participants, 57.91% presented at least one NCD. The mean scores for health lifestyle and health utility value were 11.109 and 0.944 respectively. The number of NCDs was negatively associated with health utility value, while positively correlated with the health lifestyle score (P<0.001). The results of hierarchical regression indicated that health lifestyle exerted a negative moderating effect on the relationship between the number of NCDs and HRQoL (ß=0.006, P<0.001), which was also observed for specific health-related behaviors such as sleep duration (ß=0.013, P<0.001), physical examination attendance (ß=0.006, P<0.05) and physical activity (ß=0.013, P<0.001). Conclusion: These findings highlight the crucial role of a healthy lifestyle in attenuating the association between the number of NCDs and HRQoL. Recognizing the potential modulating influence of a healthy lifestyle in this relationship could be pivotal for developing effective interventions for this population, even within resource-constrained rural settings.
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BACKGROUND: Rice (Oryza sativa L.) is one of the most important food crops in the world and the application of nitrogen fertilizer is an effective means of ensuring stable and high rice yields. However, excessive application of nitrogen fertilizer not only causes a decline in the quality of rice, but also leads to a series of environmental costs. Nitrogen reutilization is closely related to leaf senescence, and nitrogen deficiency will lead to early functional leaf senescence, whereas moderate nitrogen application will help to delay leaf senescence and promote the production of photosynthetic assimilation products in leaves to achieve yield increase. Therefore, it is important to explore the mechanism by which nitrogen affects rice senescence, to search for genes that are tolerant to low nitrogen, and to delay the premature senescence of rice functional leaves. RESULTS: The present study was investigated the transcriptional changes in flag leaves between full heading and mature grain stages of rice (O. sativa) sp. japonica 'NanGeng 5718' under varying nitrogen (N) application: 0 kg/ha (no nitrogen; 0N), 240 kg/ha (moderate nitrogen; MN), and 300 kg/ha (high nitrogen; HN). Compared to MN condition, a total of 10427 and 8177 differentially expressed genes (DEGs) were detected in 0N and HN, respectively. We selected DEGs with opposite expression trends under 0N and HN conditions for GO and KEGG analyses to reveal the molecular mechanisms of nitrogen response involving DEGs. We confirmed that different N applications caused reprogramming of plant hormone signal transduction, glycolysis/gluconeogenesis, ascorbate and aldarate metabolism and photosynthesis pathways in regulating leaf senescence. Most DEGs of the jasmonic acid, ethylene, abscisic acid and salicylic acid metabolic pathways were up-regulated under 0N condition, whereas DEGs related to cytokinin and ascorbate metabolic pathways were induced in HN. Major transcription factors include ERF, WRKY, NAC and bZIP TF families have similar expression patterns which were induced under N starvation condition. CONCLUSION: Our results revealed that different nitrogen levels regulate rice leaf senescence mainly by affecting hormone levels and ascorbic acid biosynthesis. Jasmonic acid, ethylene, abscisic acid and salicylic acid promote early leaf senescence under low nitrogen condition, ethylene and ascorbate delay senescence under high nitrogen condition. In addition, ERF, WRKY, NAC and bZIP TF families promote early leaf senescence. The relevant genes can be used as candidate genes for the regulation of senescence. The results will provide gene reference for further genomic studies and new insights into the gene functions, pathways and transcription factors of N level regulates leaf senescence in rice, thereby improving NUE and reducing the adverse effects of over-application of N.
Subject(s)
Gene Expression Profiling , Nitrogen , Oryza , Plant Leaves , Transcription Factors , Oryza/genetics , Oryza/growth & development , Oryza/metabolism , Oryza/physiology , Nitrogen/metabolism , Plant Leaves/genetics , Plant Leaves/metabolism , Plant Leaves/growth & development , Transcription Factors/genetics , Transcription Factors/metabolism , Plant Senescence/genetics , Gene Expression Regulation, Plant , Biosynthetic Pathways/genetics , Transcriptome , Fertilizers , Genes, PlantABSTRACT
Defect engineering and nitrogen doping being effective strategies for modulating the surface chemical state of the carbon matrix have been widely explored to promote the catalytic activity in the territory of electrochemical energy storage and conversion devices. However, the controllable synthesis of carbon material with high-density specific defects and high nitrogen doping is still full of challenges. Here, we first synthesize one-dimensional necklace-like nitrogen-doped carbon nanochains (N-CNCs) with abundant defects on carbon fiber paper (CFP) by chemical vapor deposition (CVD) method. The resultant nanostructures are a bunch of interconnected carbon spheres with a hollow structure at the internode and present the complete one-dimensional nanochain configuration. Specifically, the N-CNCs with a corrugated surface possesses high content of sp3 defects (31.2%) and nitrogen (23.6 at %). Combining finite element analysis and experimental results, it reveals that the robust shear field generated by etching gas releasing from thermal decomposition of melamine in situ modulates the CVD process via changing the size and force environment of the metal catalyst droplets for formation of N-CNCs. Benefiting from the high ratio of sp3/sp2 and nitrogen doped on the surface, the N-CNCs@CFP displays a superior electrocatalytic performance for CO2RR, delivering CO Faradaic efficiency of 95.9% and a current density of 23.2 mA cm-2 at -0.86 V vs RHE. This work provides promising synthesis strategy and some inspirations for construction of ultradense and specific defects coupling with nitrogen doping sites into carbon materials to achieve high-efficiency electrocatalysis applications.
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The traditional chemotherapeutic agents' disadvantages such as high toxicity, untargeting and poor water solubility lead to disappointing chemotherapy effects, which restricts its clinical application. In this work, novel size-appropriate and glutathione (GSH)-responsive nano-hydrogels were successfully prepared via the active ester method between chitosan (containing -NH2) and cross-linker (containing NHS). Especially, the cross-linker was elaborately designed to possess a disulfide linkage (SS) as well as two terminal NHS groups, namely NHS-SS-NHS. These functionalities endowed chitosan-based cross-linked scaffolds with capabilities for drug loading and delivery, as well as a GSH-responsive mechanism for drug release. The prepared nano-hydrogels demonstrated excellent performance applicable morphology, excellent drug loading efficiency (â¼22.5%), suitable size (â¼100 nm) and long-term stability. The prepared nano-hydrogels released over 80% doxorubicin (DOX) after incubation in 10 mM GSH while a minimal DOX release less than 25% was tested in normal physiological buffer (pH = 7.4). The unloaded nano-hydrogels did not show any apparent cytotoxicity to A 549 cells. In contrast, DOX-loaded nano-hydrogels exhibited marked anti-tumor activity against A 549 cells, especially in high GSH environment. Finally, through fluorescent imaging and flow cytometry analysis, fluorescein isothiocyanate-labeled nano-hydrogels show obvious specific binding to the GSH high-expressing A549 cells and nonspecific binding to the GSH low-expressing A549 cells. Therefore, with this cross-linking approach, our present finding suggests that cross-linked chitosan nano-hydrogel drug carrier improves the anti-tumor effect of the A 549 cells and may serve as a potential injectable delivery carrier.
Subject(s)
Antineoplastic Agents , Chitosan , Cross-Linking Reagents , Doxorubicin , Glutathione , Hydrogels , Chitosan/chemistry , Humans , Doxorubicin/pharmacology , Doxorubicin/chemistry , Glutathione/chemistry , Glutathione/metabolism , Hydrogels/chemistry , Cross-Linking Reagents/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Survival/drug effects , Drug Liberation , Cell Line, Tumor , A549 Cells , Drug Carriers/chemistry , Drug Delivery Systems , Disulfides/chemistry , Delayed-Action Preparations/chemistryABSTRACT
INTRODUCTION: Hydrogen (H2) is regarded as a novel therapeutic agent against several diseases owing to its inherent biosafety. Bronchopulmonary dysplasia (BPD) has been widely considered among adverse pregnancy outcomes, without effective treatment. Placenta plays a role in defense, synthesis, and immunity, which provides a new perspective for the treatment of BPD. This study aimed to investigate if H2 reduced the placental inflammation to protect the neonatal rat against BPD damage and potential mechanisms. METHODS: We induced neonatal BPD model by injecting lipopolysaccharide (LPS, 1 µg) into the amniotic fluid at embryonic day 16.5 as LPS group. LPS + H2 group inhaled 42% H2 gas (4 h/day) until the samples were collected. We primarily analyzed the neonatal outcomes and then compared inflammatory levels from the control group (CON), LPS group and LPS + H2 group. HE staining was performed to evaluate inflammatory levels. RNA sequencing revealed dominant differentially expressed genes. Bioinformatics analysis (GO and KEGG) of RNA-seq was applied to mine the signaling pathways involved in protective effect of H2 on the development of LPS-induced BPD. We further used qRT-PCR, Western blot and ELISA methods to verify differential expression of mRNA and proteins. Moreover, we verified the correlation between the upstream signaling pathways and the downstream targets in LPS-induced BPD model. RESULTS: Upon administration of H2, the inflammatory infiltration degree of the LPS-induced placenta was reduced, and infiltration significantly narrowed. Hydrogen normalized LPS-induced perturbed lung development and reduced the death ratio of the fetus and neonate. RNA-seq results revealed the importance of inflammatory response biological processes and Toll-like receptor signaling pathway in protective effect of hydrogen on BPD. The over-activated upstream signals [Toll-like receptor 4 (TLR4), nuclear factor kappa-B p65 (NF-κB p65), Caspase1 (Casp1) and NLR family pyrin domain containing 3 (NLRP3) inflammasome] in LPS placenta were attenuated by H2 inhalation. The downstream targets, inflammatory cytokines/chemokines [interleukin (IL)-6, IL-18, IL-1ß, C-C motif chemokine ligand 2 (CCL2) and C-X-C motif chemokine ligand 1 (CXCL1)], were decreased both in mRNA and protein levels by H2 inhalation in LPS-induced placentas to rescue them from BPD. Correlation analysis displayed a positive association of TLR4-mediated signaling pathway both proinflammatory cytokines and chemokines in placenta. CONCLUSION: H2 inhalation ameliorates LPS-induced BPD by inhibiting excessive inflammatory cytokines and chemokines via the TLR4-NFκB-IL6/NLRP3 signaling pathway in placenta and may be a potential therapeutic strategy for BPD.
Subject(s)
Bronchopulmonary Dysplasia , Hydrogen , Inflammation , Lipopolysaccharides , NF-kappa B , NLR Family, Pyrin Domain-Containing 3 Protein , Placenta , Signal Transduction , Toll-Like Receptor 4 , Female , Pregnancy , Lipopolysaccharides/toxicity , Hydrogen/pharmacology , Hydrogen/therapeutic use , Animals , Placenta/metabolism , Placenta/drug effects , Toll-Like Receptor 4/metabolism , Toll-Like Receptor 4/genetics , Signal Transduction/drug effects , Rats , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , NF-kappa B/metabolism , Inflammation/metabolism , Inflammation/drug therapy , Administration, Inhalation , Bronchopulmonary Dysplasia/metabolism , Bronchopulmonary Dysplasia/chemically induced , Bronchopulmonary Dysplasia/drug therapy , Bronchopulmonary Dysplasia/prevention & control , Interleukin-6/metabolism , Interleukin-6/genetics , Rats, Sprague-Dawley , Disease Models, AnimalABSTRACT
Objective: To observe the efficacy of different anti-infective treatment regimens on acute appendicitis in children, a retrospective study was conducted by collecting previous cases. Methods: Ninety children with acute appendicitis who received laparoscopic appendectomy from May 2020 to September 2022 were included in this retrospective study. According to the different anti-infective treatment regimens, they were divided into Piperacillin-Tazobactam group, Piperacillin-Tazobactam+Metronidazole group, and Cefminox+Metronidazole group (n=30). Three groups of children received medication treatment before surgery. The postoperative recovery, treatment effect, bacterial clearance, complication rate, pharmacoeconomic evaluation, and adverse reactions were compared. Results: The effective rates in the three groups were 83.33%, 90.00%, and 90.00%, respectively (P > .05). There were no differences in the bacterial clearance, complication incidence, and incidence of pharmaceutical side effects among the three groups (P > .05). The total hospitalization cost, total drug cost, and antimicrobial drug cost in Cefminox + Metronidazole group were lower than those in Piperacillin-Tazobactam group and Piperacillin-Tazobactam + Metronidazole group, respectively (P < .05). The intensity of antibacterial drug use in Piperacillin-Tazobactam group was the lowest, followed by Piperacillin-Tazobactam + Metronidazole group and Cefminox + Metronidazole group (P < .05). Conclusion: The three anti-infective regimens have the same therapeutic effect on acute appendicitis in children. However, the regimen of Cefminox + Metronidazole is the most economical option and can be used as the preferred treatment for acute appendicitis in children. As the preferred treatment for acute appendicitis in children. The Piperacillin-Tazobactam group has the lowest intensity of antibiotic use and can reduce bacterial resistance.
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Source-sink relationships influence photosynthesis. So far, the limiting factors for photosynthesis of wheat cultivars with different source-sink relationships have not been determined. We aimed to determine the variation patterns of photosynthetic characteristics of wheat cultivars with different source-sink relationships. In this study, two wheat cultivars with different source-sink relationships were selected for photosynthetic physiological analyses. The results showed that YM25 (source-limited cultivar) had higher photosynthetic efficiency compared to YM1 (sink-limited cultivar). This is mainly due to a stronger photochemical efficiency, electron transfer capacity, and Rubisco carboxylation capacity of YM25. YM25 accumulated less soluble carbohydrates in flag leaves than YM1. This is mainly due to the stronger sucrose synthesis and transport capacity of YM25 by presenting higher sucrose-related enzyme activities and gene expression. A PCA analysis showed that Rubisco was the main factor limiting the photosynthetic capacity of YM25. The soluble sugar accumulation in flag leaves and sink limitation decreased the photosynthetic activity of YM1. Increased N application improved source-sink relationships and increased grain yield and source leaf photosynthetic capacity in both two wheat cultivars. Taken together, our findings suggest that Rubisco and sucrose synthesis and translocation are involved in the regulation of photosynthesis of wheat cultivars with different source-sink relationships and that source and sink limitation effects should be considered in photosynthesis.
Subject(s)
Ribulose-Bisphosphate Carboxylase , Triticum , Triticum/genetics , Photosynthesis , Carbohydrate Metabolism , SucroseABSTRACT
BACKGROUND: Diabetic foot ulcer (DFU) is a common and serious complication of diabetes, and its treatment is challenging. Platelet-rich plasma (PRP) gel and umbilical cord mesenchymal stem cells (UC-MSCs) gel have been concerned as new therapies for DFU in recent years, and comparative studies on the efficacy and mechanisms of these methods, however, are rarely reported. METHODS: Thirty patients with DFU were selected and divided into the PRP group and the UC-MSCs group, and wound healing, foot blood vessels (ABI index), infection index (CRP), neuropathy symptoms (TCSS score), and foot skin temperature before and after treatment were compared between the two groups. SPSS 21.0 was used for statistical analysis. RESULTS: The results showed that the efficacy of the UC-MSCs gel group was significantly better than that of the PRP group in terms of wound healing rate, time to complete wound closure, ABI index, CRP level and TCSS score. No statistically significant difference in foot skin temperature was observed between the two groups. CONCLUSION: The efficacy of UC-MSCs gel is significantly superior to that of PRP gel in the treatment of DFU, with shortened time to complete wound closure, increased wound healing rate, better pain and infection control, and improved vascular and neurological symptoms.
Subject(s)
Diabetic Foot , Mesenchymal Stem Cells , Platelet-Rich Plasma , Humans , Diabetic Foot/therapy , Skin , Umbilical CordABSTRACT
The development of efficient bifunctional catalysts for overall water splitting is highly desirable and essential for the advancement of hydrogen technology. In this work, Mo-Ni(OH)2/FexNiy(OH)3x+2y with hierarchical nanotube structure is constructed on flexible carbon cloth (CC) through simple electrochemical deposition and hydrothermal method. The hollow tube-structure is in favor of both exposing active sites and enhancing mass transfer capability. Moreover, the doping of Mo can enhance the electronic conductivity of heterostructures. The interfacial interaction between amorphous and crystal can enhance effectively the charge transfer kinetics across the interface. Therefore, Mo-Ni(OH)2/FexNiy(OH)3x+2y can achieve a low overpotential of 57 mV for hydrogen evolution reaction (HER) and 229 mV for oxygen evolution reaction (OER) at 10 mA·cm-2. In addition, Mo-Ni(OH)2/FexNiy(OH)3x+2y needs a potential of only 1.54 V at 10 mA·cm-2 for overall water splitting, and retains for a long period of time (60 h) reliable. The work will provide a valuable approach to the construction of highly efficient electrocatalysts for overall water splitting.
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OBJECTIVE: The aim of this study was to assess the ability of the modified contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) to distinguish malignancy in patients without known hepatocellular carcinoma (HCC) risk factors and compare diagnostic accuracy with that of the World Federation for Ultrasound in Medicine and Biology (WFUMB) guideline across radiologists with different levels of CEUS experience. METHODS: A total of 848 individuals with no hepatitis infection presenting with 870 lesions in non-cirrhotic livers were included and divided into the Testing and Validation groups. The modified CEUS LI-RADS was proposed, including downgrading of focal nodular hyperplasia with typical features. Diagnostic performance of the modified CEUS LI-RADS was assessed in the Testing group. In the Validation group, two radiologists with more than 9 y of CEUS experience (Experts) and two radiologists with less than 6 mo of CEUS experience (Novices) used both the modified CEUS LI-RADS and the WFUMB guideline to evaluate performance in diagnosis of the lesions. RESULTS: LR-5 + M (combination of modified LR-5 and modified LR-M) revealed optimal performance with a sensitivity, specificity and area under the curve (AUC) of 99.3%, 81.6% and 0.904, respectively. Novices using the modified CEUS LI-RADS outperformed those using the WFUMB guideline (AUC: 0.858 vs. 0.767, p = 0.005). Additionally, the sensitivity, specificity and AUC of Novices were comparable to those of Experts using the modified CEUS LI-RADS (94.1%, 77.6% and 0.858 vs. 96.1%, 77.6% and 0.868 for experts, respectively). CONCLUSION: The modified CEUS LI-RADS is a valuable method for distinguishing hepatic malignancy in patients without HCC risk factors. This is particularly beneficial for radiologists with limited CEUS expertise.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Contrast Media , Retrospective Studies , Risk Factors , Biology , Magnetic Resonance Imaging/methods , Sensitivity and SpecificityABSTRACT
To explore the anti-tumor effects of Radix Astragali on osteosarcoma and its mechanism. We analyzed the PPI network of Radix Astragali's potential targets for treating osteosarcoma and got the hub targets. We used KM curves to screen hub targets that could prolong sarcoma patients' survival time. We performed GO and KEGG enrichment analysis of Radix Astragali's potential targets and predicted Radix Astragali's molecular mechanism and function in treating osteosarcoma. The binding process between the hub targets, which could prolong sarcoma patients' survival time, and Radix Astragali was simulated through molecular docking. PPI network analysis of potential therapeutic targets discriminated 25 hub targets. The KM curves of the hub targets showed there were 13 hub targets that were effective in improving the 5-year survival rate of sarcoma patients. GO and KEGG enrichment demonstrated that Radix Astragali regulates multiple signaling pathways of osteosarcoma. Molecular docking results indicated that Radix Astragali could bind freely to the hub target, which could prolong the sarcoma patient's survival time. Radix Astragali act on osteosarcoma by regulating a signaling network formed by hub targets connecting multiple signaling pathways. Radix Astragali has the potential to become a drug for treating osteosarcoma and prolonging the sarcoma patient's survival time.
Subject(s)
Bone Neoplasms , Drugs, Chinese Herbal , Osteosarcoma , Sarcoma , Soft Tissue Neoplasms , Humans , Molecular Docking Simulation , Network Pharmacology , Osteosarcoma/drug therapy , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Bone Neoplasms/drug therapyABSTRACT
Phase-change materials (PCMs) are promising thermal storage medium for thermal management due to their efficient thermal energy harvesting capabilities. However, the low thermal conductivity (TC) and poor shape stability of PCMs have hindered their practical applications. Construction of an interconnected three-dimensional (3D) heat-conductive structure is an effective way to build phonon conduits and provide PCM confinement. Phonon scattering at the interface is an unavoidable effect that undermines the TC improvement in the PCM composite and necessitates careful engineering. This study focuses on creating a highly thermally conductive 3D carbon-bonded graphite fiber (CBGF) network to enhance the TC of the PCM, with attention especially on thermal interface engineering considering both filler-matrix (F-M) and filler-filler (F-F) interfaces. The composite with an optimized proportion of F-M and F-F interface area achieves the highest TC of 45.48 W·m-1·K-1, which is 188.5 times higher than that of the pure PCM, and a high TC enhancement per volume fraction of the filler (TCEF) of 831% per 1 vol % loading. This also results in an enhanced spatial construction for PCM confinement during the phase change. The results emphasize the significance of interface engineering in creating high-TC and form-stable phase-change composites, providing insightful guidance for rational structural design.
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Liver fibrosis remains a serious problem affecting the health of millions of people worldwide. Hepatic stellate cells (HSCs) are the main effector cells in liver fibrosis and their activation could lead to extracellular matrix deposition, which may aggravate the development of liver fibrosis and inflammation. Previous studies have reported the potential of Phillygenin (PHI) as a hepatoprotective agent to inhibit HSCs activation and fibrosis development. However, the poor water solubility of PHI hinders its clinical application as a potential anti-liver fibrosis therapy. Milk-derived exosomes (mEXO) serve as scalable nanocarriers for delivering chemotherapeutic agents due to their excellent biocompatibility. Here, we developed a PHI-Hyaluronic acid (HA) composite mEXO (PHI-HA-mEXO) drug delivery system, in which DSPE-PEG2000-HA was conjugated to the surface of mEXO to prepare HA-mEXO, and PHI was encapsulated into HA-mEXO to form PHI-HA-mEXO. As a specific receptor for HA, CD44 is frequently over-expressed during liver fibrosis and highly expressed on the surface of activated HSCs (aHSCs). PHI-HA-mEXO can bind to CD44 and enter aHSCs through endocytosis and release PHI. PHI-HA-mEXO drug delivery system can significantly induce aHSCs death without affecting quiescent HSCs (qHSCs) and hepatocytes. Furthermore, we carried out in vitro and in vivo experiments and found that PHI-HA-mEXO could alleviate liver fibrosis through aHSCs-targeted mechanism. In conclusion, the favorable biosafety and superior anti-hepatic fibrosis effects suggest a promising potential of PHI-HA-mEXO in the treatment of hepatic fibrosis. However, detailed pharmokinetics and dose-responsive experiments of PHI-HA-mEXO and the mechanism of mEXO loading drugs are still required before PHI-HA-mEXO can be applied clinically.
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Dezocine is a partial mu opioid receptor agonist previously used as an analgesic for perioperative acute pain in the US and is now the most used perioperative analgesic in China. In general, dezocine is well-tolerated, with relatively minimal risk of fatal respiratory depression. To our knowledge, there are no reports of dezocine addiction, which suggests that the abuse liability of dezocine is low. The overarching goal of this study was to determine the efficacy of a novel formulation of dezocine (Cyc-dezocine), developed for intraperitoneal or intranasal administration, to reduce voluntary opioid taking in rats. One cohort of male rats self-administered intravenous oxycodone on a fixed-ratio 5 schedule of reinforcement. Once oxycodone taking stabilized, rats were pretreated with systemic injections of vehicle or Cyc-dezocine. Cyc-dezocine dose-dependently reduced intravenous oxycodone self-administration. A second cohort of male and female rats self-administered oral oxycodone from drinking water. Once oxycodone taking stabilized, rats were pretreated with intra-nasal Cyc-dezocine. Consistent with the effects of i.p. Cyc-dezocine in our intravenous oxycodone studies, intra-nasal Cyc-dezocine attenuated oral oxycodone self-administration. Together, these findings support the need for further studies investigating the therapeutic potential of Cyc-dezocine for treating opioid use disorder.
Subject(s)
Analgesics, Opioid , Oxycodone , Humans , Rats , Male , Female , Animals , Oxycodone/pharmacology , Oxycodone/therapeutic use , Tetrahydronaphthalenes/pharmacology , Analgesics/pharmacology , Dose-Response Relationship, Drug , Receptors, Opioid, mu/agonistsABSTRACT
To enhance the oxidation resistance of Mo-based TZM alloy (Mo-0.5Ti-0.1Zr-0.02C, wt%), a novel MoSi2-ZrB2 composite coating was applied on the TZM substrate by a two-step process comprising the in situ reaction of Mo, Zr, and B4C to form a ZrB2-MoB pre-layer followed by pack siliconizing. The as-packed coating was composed of a multi-layer structure, consisting of a MoB diffusion layer, an MoSi2-ZrB2 inner layer, and an outer layer of mixture of MoSi2 and Al2O3. The composite coating could provide excellent oxidation-resistant protection for the TZM alloy at 1600 °C. The oxidation kinetic curve of the composite coating followed the parabolic rule, and the weight gain of the coated sample after 20 h of oxidation at 1600 °C was only 5.24 mg/cm2. During oxidation, a dense and continuous SiO2-baed oxide scale embedded with ZrO2 and ZrSiO4 particles showing high thermal stability and low oxygen permeability could be formed on the surface of the coating by oxidation of MoSi2 and ZrB2, which could hinder the inward diffusion of oxygen at high temperatures. Concurrently, the MoB inner diffusion layer played an important role in hindering the diffusion of Si inward with regard to the TZM alloy and could retard the degradation of MoSi2, which could also improve the long life of the coating.
ABSTRACT
BACKGROUND: Diabetes mellitus (DM) is considered to be a risk factor in carcinogenesis and progression, although the biological mechanisms are not well understood. Here we demonstrate that platelet-endothelial cell adhesion molecule 1 (PECAM-1) internalization drives ß-catenin-mediated endothelial-mesenchymal transition (EndMT) to link DM to cancer. METHODS: The tumor microenvironment (TME) was investigated for differences between colon cancer with and without DM by mRNA-microarray analysis. The effect of DM on colon cancer was determined in clinical patients and animal models. Furthermore, EndMT, PECAM-1 and Akt/GSK-3ß/ß-catenin signaling were analyzed under high glucose (HG) and human colon cancer cell (HCCC) supernatant (SN) or coculture conditions by western and immunofluorescence tests. RESULTS: DM promoted the progression and EndMT occurrence of colon cancer (CC). Regarding the mechanism, DM induced PECAM-1 defection from the cytomembrane, internalization and subsequent accumulation around the cell nucleus in endothelial cells, which promoted ß-catenin entry into the nucleus, leading to EndMT occurrence in CC with DM. Additionally, Akt/GSK-3ß signaling was enhanced to inhibit the degradation of ß-catenin, which regulates the process of EndMT. CONCLUSIONS: PECAM-1 defects and/or internalization are key events for ß-catenin-mediated EndMT, which is significantly boosted by enhanced Akt/GSK-3ß signaling in the DM-associated TME. This contributes to the mechanism by which DM promotes the carcinogenesis and progression of CC. Video Abstract.