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In this Letter, the CH3NH3PbBr3 nanocrystals (NCs) are embedded into the interstices of the fluorine (polyvinyl fluoride/polyvinylidene fluoride, PVF/PVDF) matrix on polyethylene terephthalate (PET) substrate to introduce new advantages, such as being flexible and waterproof, while maintaining the high optical performance of perovskites. The sample's photoluminescence (PL) spectra under 325â nm laser is a green emission peaked at 537â nm with full width at half maximum (FWHM) of about 21.2â nm and a fast PL decay time. As a color converter, it shows high optical absorption and can transform light from solar-blind ultraviolet to a blue region into a green region in air, water, and bending conditions. While excited by a 270â nm ultraviolet light-emitting diode (LED), the system's observed -3â dB bandwidth with the color converter is near 4.4â MHz in air and water conditions with well-eye diagrams at a data rate of 30â Mbps. Finally, we demonstrate an audio transmission application with an ultraviolet light source, a color conversion layer, and a low-cost silicon-based photodetector.
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Methylammonium lead halide perovskites with highly efficient pure-color or white-light generation have gained increasing scientific interest and promote the development of a great commercial opportunity in displays, lighting, and other applications. However, the poor stabilities, lead toxicity, and unfriendly solvents and ligands in the growth process severely restrict their commercial application. Here, we proposed a green method for preparing uniform and stable polymer-encapsulated photoluminescence (PL) tunable CH3NH3PbBr3-xClx NC thin films at room temperature. Utilizing the swelling effect between alcohol compounds and organic polymers and the ionization of NaCl in methanol solution, the anion exchange process can be achieved rapidly within 7 min. Moreover, the PL wavelengths of the CH3NH3PbBr3-xClx NCs films were precisely tuned with steps as fine as 2 nm. Experimental results showed that NaCl dissolved in methanol solution can form Cl-(CH3OH)n, which brings ionized Cl into the polymer-encapsulated CH3NH3PbBr3 NCs film for CH3NH3PbBr3-xClx NCs film growth. Based on the swelling and anion exchange dynamics, a modified NaCl-CH3OH-MABr solution system was developed to trigger CH3NH3PbBr3-xClx NCs film PL emission tuning from 528 to 463 nm with several-fold intensity enhancement. The realization of precisely controlled photoluminescence from the perovskite nanocrystal film would have wide applications in the optical and imaging fields.
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BACKGROUND: Many adolescents experience depression that often goes undetected and untreated. Identifying children and adolescents at a high risk of depression in a timely manner is an urgent concern. While the Children's Depression Inventory (CDI) is widely utilized in China, it lacks a localized revision or simplified version. With its 27 items requiring professional administration, the original CDI proves to be a time-consuming method for predicting children and adolescents with high depression risk. Hence, this study aimed to develop a shortened version of the CDI to predict high depression risk, thereby enhancing the efficiency of prediction and intervention. METHODS: Initially, backward elimination is conducted to identify various version of the short-form scales (e.g., three-item and five-item versions). Subsequently, the performance of five machine learning (ML) algorithms on these versions is evaluated using the area under the ROC curve (AUC) to determine the best algorithm. The chosen algorithm is then utilized to model the short-form scales, facilitating the identification of the optimal short-form scale based on predefined evaluation metrics. Following this, evaluation metrics are computed for all potential decision thresholds of the optimal short-form scale, and the threshold value is determined. Finally, the reliability and validity of the optimal short-form scale are assessed using a new sample. RESULTS: The study identified a five-item short-form CDI with a decision threshold of 4 as the most appropriate scale considering all assessment indicators. The scale had 81.48% fewer items than the original version, indicating good predictive performance (AUC = 0.81, Accuracy = 0.83, Recall = 0.76, Precision = 0.71). Based on the test of 315 middle school students, the results showed that the five-item CDI had good measurement indexes (Cronbach's alpha = 0.72, criterion-related validity = 0.77). CONCLUSIONS: This five-item short-form CDI is the first shortened and revised version of the CDI in China based on large local data samples.
Subject(s)
Depression , Machine Learning , Humans , Adolescent , Child , Female , Male , China , Depression/diagnosis , Reproducibility of Results , Psychiatric Status Rating Scales/standards , Psychometrics , AlgorithmsABSTRACT
Objective: Currently, there is little information about the risk of sudden cardiac death and its predictors in aortic valve stenosis patients after transcatheter aortic valve replacement (TAVR). Therefore, we conducted a large sample cohort study on TAVR patients to evaluate the predictive factors and incidence of heart failure death caused by advanced heart failure (AHF) and sudden cardiac death. Furthermore, a nomogram model to predict its risk was constructed. Methods: This study retrospectively analyzed the data of 241 consecutive participants who had received TAVR treatment for aortic valve stenosis in our hospital from January 2020 to January 2022. The characteristics of the subjects, including myocardial zymogram, renal function, biochemical parameters, and cardiac ultrasound parameters, were collected. Moreover, a nomogram was constructed to predict the risk of sudden cardiac death and its predictors in patients after transcatheter aortic valve replacement (TAVR). The model was validatedinternally using measures of calibration and decision curve analysis. Results: Six independent risk factors(Age, smoking, diabetes, glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, and fasting blood glucose) were finally recruited into the nomogram model to predict the risk of advanced heart failure and/or cardiogenic shock in AS patients treated by TAVR. Besides, the decision curve analysis and receiver operating characteristic curve indicated that the nomogram prediction models showed positive clinical benefits. Conclusions: The Age, smoking, diabetes, glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, and fasting blood glucose are the independent risk factors for advanced heart failure and/or cardiogenic shock in AS patients treated by TAVR. The construction of nomograms is beneficial in predicting the risk of advanced heart failure and/or cardiogenic shock in AS patients treated by TAVR.
Subject(s)
Aortic Valve Stenosis , Heart Failure , Nomograms , Shock, Cardiogenic , Transcatheter Aortic Valve Replacement , Humans , Transcatheter Aortic Valve Replacement/adverse effects , Aortic Valve Stenosis/surgery , Aortic Valve Stenosis/complications , Female , Male , Retrospective Studies , Aged , Shock, Cardiogenic/etiology , Aged, 80 and over , Risk FactorsABSTRACT
In the case of CO2 thermal-catalytic hydrogenation, highly selective olefin generation and subsequent olefin secondary reactions to fuel hydrocarbons in an ultra-short residence time is a huge challenge, especially under industrially feasible conditions. Here, we report a pioneering synthetic process that achieves selective production of high-volume commercial gasoline with the assistance of fast response mechanism. In situ experiments and DFT calculations demonstrate that the designed NaFeGaZr presents exceptional carbiding prowess, and swiftly forms carbides even at extremely brief gas residence times, facilitating olefin production. The created successive hollow zeolite HZSM-5 further reinforces aromatization of olefin diffused from NaFeGaZr via optimized mass transfer in the hollow channel of zeolite. Benefiting from its rapid response mechanism within the multifunctional catalytic system, this catalyst effectively prevents the excessive hydrogenation of intermediates and controls the swift conversion of intermediates into aromatics, even in high-throughput settings. This enables a rapid one-step synthesis of high-quality gasoline-range hydrocarbons without any post-treatment, with high commercial product compatibility and space-time yield up to 0.9 kggasoline·kgcat-1·h-1. These findings from the current work can provide a shed for the preparation of efficient catalysts and in-depth understanding of C1 catalysis in industrial level.
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BACKGROUND: Pronation-external rotation IV (PER IV) ankle fractures are relatively uncommon among rotational ankle fractures, but they are the most severe type. Although recent studies have shown satisfactory functional recovery in PER IV after surgical treatment, the different outcomes between fracture patterns and equivalent fracture patterns have not yet been evaluated. This study aims to compare short-term outcomes in PER IV ankle injuries between fracture patterns and equivalent fracture patterns. METHODS: This retrospective study was conducted at Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou, China, from July 2023 to October 2023. A total of 41 PER IV injuries from 2018 to 2022 were included and followed for at least one year. The American Orthopaedic Foot and Ankle Society (AOFAS) AnkleHindfoot Scale, Ankle Range of Motions (ROM), and Visual Analogue Scale (VAS) for pain scores were the main outcome measures. The rate of postoperative complications was the secondary outcome measure. Patient demographics were compared in PER IV fractures and PER IV ankle equivalent fractures. RESULTS: The mean follow-up time was 18.2 ± 4.2 (range, 12-24) months. Postoperative X-ray and CT scans showed a satisfactory reduction of the ankle joint and syndesmosis. No reduction loss of distal tibiofibular syndesmosis or ankle joints was found at the 12-month follow-up. The average AOFAS scores after one year in both groups were satisfactory (fracture group vs. fracture equivalent group, 96.72 ± 4.21 vs. 92.63 ± 5.36; P < 0.05). The average VAS scores after one year in both groups were satisfactory (fracture group vs. fracture equivalent group, 1.45 ± 2.01 vs. 1.38 ± 1.96; P > 0.05). The average ROM scores after one year in both groups were satisfactory (dorsiflexion, fracture group vs. fracture equivalent group, 15.21 ± 5.62 vs. 13.46 ± 4.35; P > 0.05; plantar flexion, fracture group vs. fracture equivalent group, 38.62 ± 9.68 vs. 42.32 ± 5.28; P > 0.05). CONCLUSION: For patients with PER-IV ankle injuries, the fracture mode had a better prognosis than the fracture equivalent mode.
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BACKGROUNDS: Joint iron overload in hemochromatosis induces M1 polarization in synovial macrophages, releasing pro-inflammatory factors and leading to osteoarthritis development. However, the mechanism by which iron overload regulates M1 polarization remains unclear. This study aims to elucidate the mechanism by which synovial iron overload promotes macrophage M1 polarization. METHODS: In vitro, RAW264.7 macrophages were treated with iron and divided into five groups based on the concentration of the iron chelator, desferrioxamine (DFO): Ctrl, Fe, DFO1, DFO2, and DFO3. In vivo, rats were categorized into five groups based on iron overload and intra-articular DFO injection: A-Ctrl, A-Fe, A-DFO1, A-DFO2, and A-DFO3. Osteoarthritis was induced by transecting the left knee anterior cruciate ligament. Macrophage morphology was observed; Prussian Blue staining quantified iron deposition in macrophages, synovium, and liver; serum iron concentration was measured using the ferrozine method; cartilage damage was assessed using H&E and Safranin O-Fast Green staining; qPCR detected iNOS and Arg-1 expression; Western Blot analyzed the protein expression of iNOS, Arg-1, 4E-BP1, phosphorylated 4E-BP1, p70S6K, and phosphorylated p70S6K; ELISA measured TNF-α and IL-6 concentrations in supernatants; and immunohistochemistry examined the protein expression of F4/80, iNOS, Arg-1, 4E-BP1, phosphorylated 4E-BP1, p70S6K, and phosphorylated p70S6K in the synovium. RESULTS: In vitro, iron-treated macrophages exhibited Prussian Blue staining indicative of iron overload and morphological changes towards M1 polarization. qPCR and Western Blot revealed increased expression of the M1 polarization markers iNOS and its protein. ELISA showed elevated TNF-α and IL-6 levels in supernatants. In vivo, ferrozine assay indicated significantly increased serum iron concentrations in all groups except A-Ctrl; Prussian Blue staining showed increased liver iron deposition in all groups except A-Ctrl. Iron deposition in rat synovium decreased in a DFO concentration-dependent manner; immunohistochemistry showed a corresponding decrease in iNOS and phosphorylated 4E-BP1 expression, and an increase in Arg-1 expression. CONCLUSION: Intracellular iron overload may exacerbate joint cartilage damage by promoting synovial macrophage M1 polarization through phosphorylation of 4E-BP1 in the mTORC1-p70S6K/4E-BP1 pathway.
Subject(s)
Hemochromatosis , Iron Overload , Osteoarthritis , Animals , Rats , Ferrocyanides , Ferrozine , Hemochromatosis/metabolism , Hemochromatosis/pathology , Interleukin-6 , Iron , Mechanistic Target of Rapamycin Complex 1 , Osteoarthritis/metabolism , Osteoarthritis/pathology , Ribosomal Protein S6 Kinases, 70-kDa/metabolism , Tumor Necrosis Factor-alphaABSTRACT
Background: An accumulating number of studies show that CALD1 is associated with a variety of tumor microenvironments (TME) and is closely related to patients' survival. However, to the best of our knowledge, few studies examined the role of CALD1 in the immune microenvironment of glioma. The aim of this study is to investigate the potential correlation between CALD1 and the pathogenesis and progression of glioma, aiming to identify a novel therapeutic target. Methods: We assessed the role of CALD1 in pan-cancer and investigated the correlation between CALD1 and TME of glioma by bioinformatic analysis and experimental verification. Results: We found that CALD1 expression in glioma was associated with a variety of infiltrating immune cells. CALD1 can promote the development of glioma by affecting M2 macrophage infiltration. Also, we found that CALD1 was closely associated with tumor mutation burden, microsatellite instability, copy number variation, methylation, and stem cell index. Our clinical correlation study demonstrated that CALD1 was associated with overall survival, progression-free interval, and disease-specific survival in a variety of tumors. We verified the significantly high expression of CALD1 in glioma using quantitative real-time polymerase chain reaction (PCR) and Western blotting. Meanwhile, we also conducted relevant cell experiments to prove that CALD1 can affect the proliferation and migration ability of glioma cells in vitro. Conclusions: Our results confirmed that CALD1 may be a prognostic marker for glioma and a potential target for immunotherapy in the future.
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Recently, due to the advantages of superior compatibility, fewer interface defects, and a high electric breakdown field, all-organic dielectric composites have attracted significant research interest. In this investigation, we produced all-organic P(VDF-TrFE-CFE) terpolymer/PI (terp/PI) composite films by incorporating a small amount of terpolymer into PI substrates for high energy density capacitor applications. The resulting terp/PI-5 (5% terpolymer) composite films exhibit a permittivity of 3.81 at 1 kHz, which is 18.7% greater than that of pristine PI (3.21). Furthermore, the terp/PI-5 film exhibited the highest energy density (9.67 J/cm3) and a relatively high charge-discharge efficiency (84.7%) among the terp/PI composite films. The energy density of the terp/PI-5 film was increased by 59.8% compared to that of the pristine PI film. The TSDC results and band structure analysis revealed the presence of deeper traps in the terp/PI composites, contributing to the suppression of leakage current and improved charge-discharge efficiency. Furthermore, durability tests confirm the stability of the composite films under extended high-temperature exposure and cycling, establishing their viability for practical applications.
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Isolated anti-HBc (IAHBc) is defined by the presence of anti-HBc in the absence of HBsAg and hepatitis B surface antibody (anti-HBs). IAHBc is of great clinical significance as a specific pattern of HBV infection, but IAHBc has not been fully clarified. This study aimed to explore the prevalence and influential factors of IAHBc from routine examination results of inpatients.A total of 61,247 individuals were included in the study, with a median age of 55 years (range: 43-68), and a male-to-female ratio of 0.90:1. The prevalence of current HBV infection (HBsAg positive) was 6.82%, while the prevalence of previous HBV infection (HBsAg negative but anti-HBc positive) was 48.63%. The prevalence of IAHBc was 12.31%. Among them, the rates for males were 7.10%, 52.16%, and 13.70%, respectively, which were significantly higher than the rates for females at 6.56%, 45.45%, and 11.06% (P < 0.05). The prevalence rates mentioned above were significantly reduced after vaccination (P < 0.05). The prevalence of IAHBc increases with age, rising from 0.23% in the age group of 15-29 years to 13.57% in individuals aged 80 and above. After the age of 50, the prevalence of IAHBc closely parallels the previous infection rate but shows no significant association with the current infection rate (P > 0.05). Among IAHBc individuals, approximately 33.83% tested positive for anti-HBe, and their anti-HBc absorbance values were significantly higher compared to anti-HBe negative individuals (7.08 and 5.31, P < 0.01). The prevalence of anti-HBe positivity among IAHBc individuals does not vary with changes in the previous infection rate and age (P > 0.05).
Subject(s)
Hepatitis B Antibodies , Hepatitis B , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , China/epidemiology , Hepatitis B/epidemiology , Hepatitis B Antibodies/blood , Hepatitis B Surface Antigens , PrevalenceABSTRACT
We report zinc cobalt-layered double hydroxides (ZnCo-LDH) as the active cathode materials for the development of high-performance Zn-ZnCo batteries. Electrochemical investigations show the battery's capacity increases linearly with increasing the ZnCo-LDH loading (up to 60 mg cm-2). The resulting Zn-ZnCo battery exhibits excellent rate performance and cycle stability, retaining 86% of its capacity even after 5000 cycles of testing. By incorporating ZnCo-LDH with a Pt/C-coated gas diffusion layer to form an integrated multifunctional air-cathode, we demonstrate a hybrid Zn battery, which combines the merits of Zn-ZnCo and Zn-air batteries to show a characteristic two-stage charge-discharge voltage profile. The current work demonstrates the linear relationship between the battery capacity and the active material loading. The results also highlight that a greater battery capacity requires further increasing of loading though very challenging.
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It is widely acknowledged that we are currently facing a critical tipping point with regards to global extinction, with human activities driving us perilously close to the brink of a devastating sixth mass extinction. As a promising option for safeguarding endangered species, induced pluripotent stem cells (iPSCs) hold great potential to aid in the preservation of threatened animal populations. For endangered species, such as the northern white rhinoceros (Ceratotherium simum cottoni), supply of embryos is often limited. After the death of the last male in 2019, only two females remained in the world. IPSC technology offers novel approaches and techniques for obtaining pluripotent stem cells (PSCs) from rare and endangered animal species. Successful generation of iPSCs circumvents several bottlenecks that impede the development of PSCs, including the challenges associated with establishing embryonic stem cells, limited embryo sources and immune rejection following embryo transfer. To provide more opportunities and room for growth in our work on animal welfare, in this paper we will focus on the progress made with iPSC lines derived from endangered and extinct species, exploring their potential applications and limitations in animal welfare research.
Subject(s)
Induced Pluripotent Stem Cells , Female , Animals , Male , Humans , Endangered Species , Perissodactyla , Embryonic Stem Cells , Cell DifferentiationABSTRACT
BACKGROUND: Epilepsy is a serious neurological disorder that affects millions of people each year, often leading to cognitive issues and reduced quality of life. Medication is the main treatment, but many patients experience negative side effects. Male Sprague-Dawley (SD) rats were chosen as experimental animals for this experiment due to their physiological and genetic similarities to humans, cost-effectiveness, and ease of handling in a laboratory setting. AIMS: The objective of this study was to assess the neuroprotective properties of baicalin (BA) in relation to its impact on anxiety and depressive-like behaviors in the epilepsy model. METHODS: Thirty male Sprague-Dawley (SD) rats were selected for this experiment. Pentylenetetrazol (PTZ) kindling (40 mg/kg; i.p.) was utilized to establish an epilepsy model. The effect of BA (50 mg/kg; gavage) on seizure severity (assessed using the Racine scale), anxiety, and depressive- like behaviors (evaluated through open field experiments and forced swimming tests) was examined. Histological examinations, including hematoxylin and eosin (HE) staining and Nissl staining, were conducted to assess neuronal damage. Furthermore, the neuroprotective properties of BA were examined through the analysis of Doublecortin (DCX), MKI67 (KI67), and Brain-Derived Neurotrophic Factor (BDNF) levels in the hippocampus of rats. The inhibitory impact of BA on neuroinflammation was assessed via dual labeling for NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and the microglial marker ionized calcium- binding adapter molecule 1 (Iba-1). The influence of BA on the expression of P2X7 receptor (P2X7R), NLRP3, and Interleukin-1ß (IL-1ß) was also assessed by reverse transcription quantitative PCR (RT-qPCR) in the brain. Finally, we employed a molecular docking model to assess the extent of receptor-ligand binding. RESULTS: Epilepsy models exhibited significant anxiety and depressive-like behaviors, and BA significantly reduced the severity of seizures in these rats while also alleviating their anxiety and depressive-like behaviors. Moreover, neuronal loss and damage were observed in the hippocampus of epileptic rats, but BA was able to effectively counteract this issue by enhancing BDNF expression and promoting neurogenesis within the hippocampus, especially in the DG region. The co-localization of Iba-1 with NLRP3 indicated the activation of NLRP3 inflammasome in microglia. Subsequent RT-PCR revealed that BA may alleviate anxiety and depressive-like behaviors in epileptic rats by activating the P2RX7/NLRP3/ IL-1ß signaling pathway. The final molecular docking results indicated that BA had a good binding affinity with proteins, such as P2RX7, NLRP3, and IL-1ß. CONCLUSION: This study confirmed the effectiveness of BA in improving anxiety and depressivelike behaviors associated with epilepsy. Moreover, it provides theoretical support for the neuroprotective role demonstrated by BA.
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ETHNOPHARMACOLOGICAL RELEVANCE: Prostate cancer (PCa) is the most common malignancy of the male genitourinary system and currently lacks effective treatment. Semen Impatientis, the dried ripe seed of Impatiens balsamina L., is described by the Chinese Pharmacopoeia as a traditional Chinese medicine (TCM) and is used in clinical practice to treat tumors, abdominal masses, etc. In our previous study, the ethyl acetate extracts of Semen Impatientis (EAESI) was demonstrated to be the most effective extract against PCa among various extracts. However, the biological effects of EAESI against PCa in vivo and the specific antitumor mechanisms involved remain unknown. AIM OF THE STUDY: In this study, we aimed to investigate the antitumor effect of EAESI on PCa in vitro and in vivo by performing network pharmacology analysis, transcriptomic analysis, and experiments to explore and verify the underlying mechanisms involved. MATERIALS AND METHODS: The antitumor effect of EAESI on PCa in vitro and in vivo was investigated via CCK-8, EdU, flow cytometry, and wound healing assays and xenograft tumor models. Network pharmacology analysis and transcriptomic analysis were employed to explore the underlying mechanism of EAESI against PCa. Activating transcription factor 3 (ATF3) and androgen receptor (AR) were confirmed to be the targets of EAESI against PCa by RTâqPCR, western blotting, and rescue assays. In addition, the interaction between ATF3 and AR was assessed by coimmunoprecipitation, immunofluorescence, and nuclear-cytoplasmic separation assays. RESULTS: EAESI decreased cell viability, inhibited cell proliferation and migration, and induced apoptosis in AR+ and AR- PCa cells. Moreover, EAESI suppressed the growth of xenograft tumors in vivo. Network pharmacology analysis revealed that the hub targets of EAESI against PCa included AR, AKT1, TP53, and CCND1. Transcriptomic analysis indicated that activating transcription factor 3 (ATF3) was the most likely critical target of EAESI. EAESI downregulated AR expression and decreased the transcriptional activity of AR through ATF3 in AR+ PCa cells; and EAESI promoted the expression of ATF3 and exerted its antitumor effect via ATF3 in AR+ and AR- PCa cells. CONCLUSIONS: EAESI exerts good antitumor effects on PCa both in vitro and in vivo, and ATF3 and AR are the critical targets through which EAESI exerts antitumor effects on AR+ and AR- PCa cells.
Subject(s)
Acetates , Activating Transcription Factor 3 , Mice, Nude , Network Pharmacology , Prostatic Neoplasms , Receptors, Androgen , Xenograft Model Antitumor Assays , Male , Animals , Humans , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/pathology , Activating Transcription Factor 3/metabolism , Activating Transcription Factor 3/genetics , Receptors, Androgen/metabolism , Receptors, Androgen/genetics , Acetates/chemistry , Cell Line, Tumor , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/isolation & purification , Mice , Apoptosis/drug effects , Cell Proliferation/drug effects , Plant Extracts/pharmacology , Plant Extracts/chemistry , Transcriptome/drug effects , Mice, Inbred BALB C , Cell Movement/drug effects , Gene Expression Regulation, Neoplastic/drug effectsABSTRACT
BACKGROUND: Prostate cancer (PCa) is the most prevalent genitourinary malignancy in men, with a significant proportion of patients developing biochemical recurrence (BCR) after treatment. The immune microenvironment and metabolic alterations have crucial implications for the tumorigenesis and progression of PCa. Therefore, identifying metabolic genes associated with the immune microenvironment holds promise for predicting BCR and improving PCa prognosis. METHODS: In this study, ssGSEA and hierarchical clustering analysis were first conducted to evaluate and group PCa samples, followed by the use of the ESTIMATE and CIBERSORT algorithms to characterize the immunophenotypes and tumor microenvironment. The differential metabolic genes (MTGs) between groups were utilized to develop a prognostic-related signature. The predictive performance of the signature was assessed by principal component analysis (PCA), receiver operating characteristic (ROC) curve analysis, survival analysis, and the TIDE algorithm. A miRNA-MTGs regulatory network and predictive nomogram were constructed. Moreover, the expression of prognostic MTGs in PCa was detected by RTâqPCR. RESULTS: PCa samples from the TCGA cohort were separated into two groups: the immune-low group and immune-high group. Forty-eight differentially expressed MTGs between the groups were identified, including 37 up-regulated and 11 down-regulated MTGs. Subsequently, CEL, CYP3A4, and PDE6G were identified as the genes most strongly associated with the BCR of PCa patients and these genes were utilized to establish the MTGs-based prognostic signatures. PCA, ROC curves analysis, Kaplan-Meier survival analysis, and the nomogram all showed the good predictive ability of the signature regardless of clinical variables. Furthermore, the MTGs-based signature was indicated as a potential predictive biomarker for immunotherapy response. Nine miRNAs involved in the regulation of prognostic MTGs were determined. In addition to the CEL gene, the PDE6G and CYP3A4 genes were expressed at higher levels in PCa samples. CONCLUSIONS: The MTGs-based signature represents a novel approach with promising potential for predicting BCR in PCa patients.
Subject(s)
MicroRNAs , Prostatic Neoplasms , Male , Humans , Prognosis , Cytochrome P-450 CYP3A , MicroRNAs/genetics , Prostatic Neoplasms/genetics , Nomograms , Tumor Microenvironment/geneticsABSTRACT
pH-responsive micelles with positive charges are challenged by their significant effect on the cells/proteins and compromise their final fate due to electrostatic interactions. As one of the promising strategies, zwitterion incorporation in micelles has attracted considerable attention and displayed improved protein adsorption and blood circulation performances. However, previous reports in this field have been mostly limited in hemolysis for studying blood behaviour and lack a comprehensive understanding of their interactions with blood components. Herein, we present a prelimilary study on the effect of zwitterionic sulfobetaine incorporation on blood behaviour, phagocytosis, and in vivo biodistribution of pH-responsive micelles with positive charges. Amphiphilic triblock copolymers, namely poly(ε-caprolactone)-b-poly(N,N-diethylaminoethyl methacrylate)-(N-(3-sulfopropyl-N-methacryloxyethy-N,N-diethylammonium betaine)) (PCL-PDEAPSx, x = 2, 6, 10), containing different numbers of sulfobetaine groups were synthesized through four steps to prepare the pH-responsive micelles with positive charges. The effect of the sulfobetaine incorporation displayed different profiles, e.g., the micelles had no effect on RBC aggregation, thrombin time (TT), and platelet aggregation, while the cytotoxicity, hemolysis, RBC deformability, activated partial thromboplastin time (APTT), prothrombin time (PT), platelet activation, protein (albumin, fibrinogen, plasma) adsorption, phagocytosis, and in vivo biodistribution decreased with the increase in the sulfobetaine number, in which the transition mainly occurred at a sulfobetaine/tertiary amine group ratio of 3/7-1/1 compared to that of the mPEG control. In addition, the micelles displayed a strong inhibitory effect on the intrinsic coagulation pathway, which was associated with a significant decrease in the coagulation factor activity. Based on these findings, the related mechanism is discussed and proposed, which can aid the rational design of pH-responsive micelles for improved therapeutics.
Subject(s)
Betaine , Micelles , Humans , Tissue Distribution , Hemolysis , Phagocytosis , Hydrogen-Ion ConcentrationABSTRACT
Hemostasis, infection, oxidative stress, and inflammation still severely impede the wound repair process. It is significant to develop multifunctional wound dressings that can function as needed in various stages of wound healing. In this study, iridium nanoparticles (IrNPs) with multi-enzyme mimetic activity were complexed with chitosan (CS) and fucoidan (FD) for the first time to make a multifunctional CS/FD/IrNPs hydrogel with excellent antioxidant effect. The hydrogel has excellent physicochemical properties. In particular, the incorporation of IrNPs imparts excellent antioxidant properties to the hydrogel, which could scavenge reactive oxygen species (ROS). In addition, the hydrogel shows excellent hemostatic and antibacterial properties. The CS/FD/IrNPs hydrogel performs fast and efficient hemostasis in 21 s. Moreover, the blood loss of the CS/FD/IrNPs hydrogel group was approximately 10% of that in the control group and the antibacterial rate of CS/FD/IrNPs hydrogel against E. coli and S. aureus was up to 95 %. In vivo results demonstrate that CS/FD/IrNPs hydrogel promotes wound healing by attenuating ROS levels, reducing oxidative damage, mitigating inflammation, and accelerating angiogenesis. To summarize, the CS/FD/IrNPs hydrogel system, with hemostatic, antibacterial, antioxidant, anti-inflammatory and pro-healing activities, can be a promising and effective strategy for the treatment of clinically difficult-to-heal wounds.
Subject(s)
Anti-Bacterial Agents , Antioxidants , Chitosan , Escherichia coli , Hydrogels , Iridium , Polysaccharides , Staphylococcus aureus , Wound Healing , Chitosan/chemistry , Chitosan/pharmacology , Wound Healing/drug effects , Hydrogels/chemistry , Hydrogels/pharmacology , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Iridium/chemistry , Iridium/pharmacology , Escherichia coli/drug effects , Staphylococcus aureus/drug effects , Polysaccharides/chemistry , Polysaccharides/pharmacology , Antioxidants/pharmacology , Antioxidants/chemistry , Skin/drug effects , Reactive Oxygen Species/metabolism , Mice , Male , Hemostatics/chemistry , Hemostatics/pharmacology , Oxidative Stress/drug effects , Nanoparticles/chemistry , Metal Nanoparticles/chemistry , Rats , HumansABSTRACT
The number of patients with bone defects caused by trauma, bone tumors, and osteoporosis has increased considerably. The repair of irregular, recurring, and large bone defects poses a great challenge to clinicians. Bone tissue engineering is emerging as an appropriate strategy to replace autologous bone grafting in the repair of critically sized bone defects. However, the suitability of bone tissue engineering scaffolds in terms of structure, mechanics, degradation, and the microenvironment is inadequate. Three-dimensional (3D) printing is an advanced additive-manufacturing technology widely used for bone repair. 3D printing constructs personalized structurally adapted scaffolds based on 3D models reconstructed from CT images. The contradiction between the mechanics and degradation is resolved by altering the stacking structure. The local microenvironment of the implant is improved by designing an internal pore structure and a spatiotemporal factor release system. Therefore, there has been a boom in the 3D printing of personalized bone repair scaffolds. In this review, successful research on the preparation of highly bioadaptive bone tissue engineering scaffolds using 3D printing is presented. The mechanisms of structural, mechanical, degradation, and microenvironmental adaptations of bone prostheses and their interactions were elucidated to provide a feasible strategy for constructing highly bioadaptive bone tissue engineering scaffolds.
Subject(s)
Tissue Engineering , Tissue Scaffolds , Humans , Tissue Engineering/methods , Tissue Scaffolds/chemistry , Bone and Bones/diagnostic imaging , Bone and Bones/surgery , Printing, Three-DimensionalABSTRACT
Fucoidan (FC) is known for its antioxidant properties, but it has unclear effects and mechanisms on weaned piglets. Two experiments were conducted to determine the optimal FC dosage in piglet diets and its protective effect against lipopolysaccharide (LPS)-induced oxidative stress. In experiment one, 24 low weight weaned piglets were randomly assigned to four dietary treatments: a basal diet (FC 0), or a diet supplemented with 150 (FC 150), 300 (FC 300), or 600 mg/kg FC (FC 600). In experiment two, 72 low-weaning weight piglets were randomly allocated into four treatments: a basal diet (CON), or 300 mg/kg of fucoidan added to a basal diet challenged with LPS (100 µg LPS/kg body weight) or not. The results showed that FC treatments increased the G:F ratio, and dietary FC 300 reduced the diarrhea incidence and increased the plasma IGF-1 concentrations. In addition, FC 300 and FC 600 supplementation increased the plasma SOD activity and reduced the plasma MDA concentration. LPS challenge triggered a strong systemic redox imbalance and mitochondrial dysfunction. However, dietary FC (300 mg/kg) supplementation increased the activity of antioxidant enzymes, including SOD, decreased the MDA concentration in the plasma and liver, down-regulated Keap1 gene expression, and up-regulated Nrf2, CAT, MFN2, SDHA, and UQCRB gene expression in the liver. These results indicated that dietary fucoidan (300 mg/kg) supplementation improved the growth performance and antioxidant capacity of low-weaning weight piglets, which might be attributed to the modulation of the Keap1/Nrf2 signaling pathway and the mitochondrial function in the liver.
ABSTRACT
Tuning CO2 hydrogenation product distribution to obtain high-selectivity target products is of great significance. However, due to the imprecise regulation of chain propagation and hydrogenation reactions, the oriented synthesis of a single product is challenging. Herein, we report an approach to controlling multiple sites with graphene fence engineering that enables direct conversion of CO2/H2 mixtures into different types of hydrocarbons. Fe-Co active sites on the graphene fence surface present 50.1% light olefin selectivity, while the spatial Fe-Co nanoparticles separated by graphene fences achieve liquefied petroleum gas of 43.6%. With the assistance of graphene fences, iron carbides and metallic cobalt can efficiently regulate C-C coupling and olefin secondary hydrogenation reactions to achieve product-selective switching between light olefins and liquefied petroleum gas. Furthermore, it also creates a precedent for CO2 direct hydrogenation to liquefied petroleum gas via a Fischer-Tropsch pathway with the highest space-time yields compared to other reported composite catalysts.