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OBJECTIVE: Coronary artery ectasia (CAE) is a condition characterized by the localized or widespread dilation of one or more coronary arteries. The majority of CAE patients do not present with clinical symptoms, and the exact cause of CAE remains unclear. Therefore, a retrospective analysis was conducted to explore the potential causes of CAE. METHODS: This study was a retrospective analysis of patients who underwent coronary angiography at Guangdong Provincial People's Hospital between January 2017 and July 2022, of whom 679 patients were ultimately enrolled in the study. Among them, 260 patients were diagnosed with CAE, whereas 419 patients with normal coronary results composed the control group. Remnant cholesterol (RC) was calculated as total cholesterol (TC) minus high-density lipoprotein cholesterol (HDL-C) minus low-density lipoprotein cholesterol (LDL-C). The association between RC levels and the risk of CAE was assessed via multivariable logistic models. RESULTS: Out of the 679 patients who participated in this study, with an average age of 59.9 years, 38.3% were diagnosed with CAE. Patients with CAE had higher RC levels than did those without CAE (P = 0.001). A significant positive association was observed between RC levels and the risk of CAE, with a multivariable adjusted odds ratio (OR) of 1.950 (95% confidence interval [CI]: 1.163-3.270). There was a significant positive association between RC levels and the risk of CAE in both single-vessel and multivessel dilation cases, as well as in isolated CAE and dilation secondary to coronary atherosclerosis. According to the subgroup analyses, RC levels were positively associated with the risk of CAE in participants with hypertension (OR, 1.065; 95% CI, 1.034-1.098). CONCLUSION: RC levels are positively correlated with CAE, implying that a focus on RC could be beneficial in CAE research.
Subject(s)
Cholesterol, HDL , Cholesterol, LDL , Cholesterol , Coronary Angiography , Coronary Artery Disease , Coronary Vessels , Humans , Middle Aged , Male , Female , Cross-Sectional Studies , Cholesterol/blood , Dilatation, Pathologic/blood , Retrospective Studies , Coronary Artery Disease/blood , Coronary Artery Disease/pathology , Coronary Artery Disease/diagnostic imaging , Aged , Cholesterol, LDL/blood , Coronary Vessels/pathology , Coronary Vessels/diagnostic imaging , Cholesterol, HDL/blood , Risk Factors , Triglycerides/blood , Odds RatioABSTRACT
A ferroelectric polyvinylidene fluoride (PVDF) film with excellent flexibility possesses great potential for photodetection and wearable devices. However, the relatively weak photo-absorption and the consequent small photocurrent limit its photofunctional properties. Herein, we embedded a strongly visible-light active material system, 0.5Ba(Zr0.08Ti0.8Mn0.12)O3-0.5(Ba0.7Ca0.3)TiO3 (BZTM-BCT) loaded with Ag and Au nanoparticles, into a PVDF film, which demonstrates a significantly higher photovoltaic response in the whole visible light range with a ß-phase content of over 90%. In a state of "bending + poling", the PVDF/BZTM-BCT:Au film presents an optimal response for photoelectric properties by exhibiting a photocurrent that is 57 times higher than that of a pure PVDF film when illuminated with 405 nm LED light at 100 mW cm-2. Photoexcitation and thermal excitation jointly contribute to the generation of free carriers, while the flexoelectric and ferroelectric coupling electric field provides a greater driving force for carrier separation and transport. More interestingly, composite film-based photoelectric sensors can simultaneously respond to light and the movement and deformation of contacted things, indicating its potential in versatile applications. Overall, this work puts forward a new route for designing new flexible multifunctional photoelectric devices.
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In nature, aflatoxins, especially aflatoxin B1 (AFB1), are the common mycotoxins, which cause serious health problems for humans and animals. This paper aimed to study the effects of AFB1 on flesh flavor and muscle development of grass carp (Ctenopharyngodon idella) and its mechanism. There were 1440 individual fish in total, with 6 treatments and each treatment replicated 3 times. The 6 treatments were fed a control diet with different doses of AFB1 (0.04, 29.48, 58.66, 85.94, 110.43 and 146.92 µg/kg diet) for 60 d. AFB1 increased myofiber diameter, as well as decreased myofiber density of grass carp muscle (P < 0.05). The contents of free amino acid decreased gradually (P < 0.05) as dietary AFB1 increased in the muscle of grass carp. The levels of reactive oxygen species, malonaldehyde and protein carbonyl (PC) were increased (P < 0.05) with the dietary AFB1 increased. The levels of antioxidant enzyme (glutathione peroxidase, glutathione, glutathione reductase, total antioxidant capacity, anti-superoxide anion, and anti-hydroxyl radical) were decreased (P < 0.05) with the dietary AFB1 increased. In addition, dietary AFB1 decreased the content of collagen, and downregulated the mRNA and protein levels of transforming growth factor-ß (TGF-ß)/Smads signaling pathway in grass carp muscle (P < 0.05). The mRNA and protein levels of myogenic regulatory factors were downregulated in grass carp muscle (P < 0.05). Furthermore, the activities of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) were increased (P < 0.05), and the protein levels of phosphorylate-38 mitogen-activated protein kinase (p-p38MAPK), phosphorylate-c-Jun N-terminal kinase, urokinase-type plasminogen activator (uPA), MMP-2 and MMP-9 were upregulated (P < 0.05), but collagen â , laminin ß1 and fibronectin were downregulated (P < 0.05) with the dietary AFB1 increased in the muscle of grass carp. Based on the results of this study, we can draw the following conclusion: dietary AFB1 might damage flesh flavor and inhibit the muscle development through MAPK/uPA/MMP/extracellular matrix (ECM) signaling pathway in grass carp. Moreover, the recommended safe limit of AFB1 in feed is no more than 26.77 µg/kg diet according to the PC levels in grass carp muscle.
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BACKGROUND: Rhinophyma, a late-stage subtype of rosacea, is characterized by excessive sebaceous glands and connective tissue proliferation. Patients may experience respiratory disturbances and psychological distress that significantly affect their quality of life when excessive nasal hyperplasia obstructs the external nasal valves. Surgery is the treatment of choice for rhinophyma. However, excessive bleeding, scarring, pigmentation, and high recurrence rates frequently characterize current surgical methods. AIM: To evaluate the clinical effectiveness and recurrence rates after treating severe rhinophyma with the five-blade scratcher. METHODS: This study retrospectively analyzed the clinical records of 28 patients with severe rhinophyma rosacea. The Global Flushing Severity Score (GFSS), Clinician Erythema Assessment (CEA), Rhinophyma Severity Index (RHISI), Glasgow Benefit Inventory (GBI), and satisfaction scores were used to assess the recovery of patients at 6 months and 5 years, with the recurrence rate calculated at 5 years postoperatively. In addition, the levels of pro-inflammatory factors (TNF-α, IL-1ß, and IL-6) in the serum of patients before and after surgery were detected by ELISA. RESULTS: The GFSS, CEA, and RHISI scores at 6 months and 5 years postoperatively were significantly lower than those preoperatively (P < 0.001 for both periods). Five-blade scratcher treatment greatly benefits patients as demonstrated by the GBI and patient satisfaction. A small number of patients (7/28, 25%) reported recurrence after surgical treatment for rhinophyma in our department that was not more serious than before treatment. The expression of pro-inflammatory factors (TNF-α, IL-1ß, and IL-6) in the patient's serum was significantly reduced after surgery of five-blade scratcher. CONCLUSION: The five-blade scratcher treatment demonstrates notable advantages, including simplicity, safety, efficacy, and cost-effectiveness, coupled with reduced bleeding, minimized scarring, lower recurrence rates, reduced the level of pro-inflammatory factors and improved patient satisfaction. Consequently, this therapeutic modality exhibits a viable option for individuals afflicted with severe rhinophyma.
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Herein, we designed a reaction for the desymmetrization-addition of cyclopropenes to imines by leveraging the synergy between photoredox and asymmetric cobalt catalysis. This protocol facilitated the synthesis of a series of chiral functionalized cyclopropanes with high yield, enantioselectivity, and diastereoselectivity (44 examples, up to 93% yield and >99% ee). A possible reaction mechanism involving cyclopropene desymmetrization by Co-H species and imine addition by Co-alkyl species was proposed. This study provides a novel route to important chiral cyclopropanes and extends the frontier of asymmetric metallaphotoredox catalysis.
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The meninges are critical for the brain functions, but the diversity of meningeal cell types and intercellular interactions have yet to be thoroughly examined. Here we identify a population of meningeal lymphatic supporting cells (mLSCs) in the zebrafish leptomeninges, which are specifically labeled by ependymin. Morphologically, mLSCs form membranous structures that enwrap the majority of leptomeningeal blood vessels and all the mural lymphatic endothelial cells (muLECs). Based on its unique cellular morphologies and transcriptional profile, mLSC is characterized as a unique cell type different from all the currently known meningeal cell types. Because of the formation of supportive structures and production of pro-lymphangiogenic factors, mLSCs not only promote muLEC development and maintain the dispersed distributions of muLECs in the leptomeninges, but also are required for muLEC regeneration after ablation. This study characterizes a newly identified cell type in leptomeninges, mLSC, which is required for muLEC development, maintenance, and regeneration.
Subject(s)
Endothelial Cells , Meninges , Zebrafish , Animals , Meninges/cytology , Meninges/metabolism , Endothelial Cells/metabolism , Endothelial Cells/cytology , Zebrafish Proteins/metabolism , Zebrafish Proteins/genetics , Lymphatic Vessels/cytology , Lymphatic Vessels/metabolism , Animals, Genetically Modified , Lymphangiogenesis/physiology , Regeneration/physiologyABSTRACT
The discipline development is the pillar for the development of traditional Chinese medicine( TCM). The academic progress in TCM is the commanding height of the discipline development of TCM. To lead and promote the development and academic progress of TCM, the China Association of Chinese Medicine has summarized the Top Ten Academic Achievements in Traditional Chinese Medicine during 2020-2022, the Major Scientific Problems, Engineering Technical Problems, and Industrial Technical Problems in Traditional Chinese Medicine during 2019-2023, and the Remarkable Research Achievements of Traditional Chinese Medicine during 2012-2022. Based on the above research reports and the research achievements awarded the national science and technology prizes in TCM in the last 20 years and according to the current situation and layout of TCM discipline development, this paper reviews the major research achievements of TCM in the last two decades and the latest research progress in TCM during 2020-2023. The major scientific, engineering technical, and industrial technical problems in TCM are analyzed and the emerging trends of TCM are prospected in accordance with the development laws and characteristics of TCM. This review provides new ideas and reference for the high-quality development of TCM in the new era.
Subject(s)
Medicine, Chinese Traditional , Medicine, Chinese Traditional/trends , China , Humans , Drugs, Chinese HerbalABSTRACT
The electrocatalytic nitrate reduction to ammonia holds significant values for water remediations and energy applications, which quests for the development of highly effective catalysts with considerable stability and selectivity. Recently, high-entropy alloys (HEAs) are attracting growing attention for electrocatalytic processes. Nonetheless, studies of HEA-based nitrate reduction to ammonia are still at the early stage, and it remains unclear how the HEA compositions affect the adsorption and activation of the reaction intermediates. Herein, high-throughput density functional theory (DFT) calculations were integrated with machine learning to investigate the dependence of nitrate adsorption on the FeCoNiCuZn HEA structures. In particular, a total of 1268 different structures were sampled and constructed from the multidimensional configuration space, followed by the DFT calculations to investigate the Gibbs free energy of nitrate adsorption (i.e., ΔGNO3) on different surface microstructures. Four regression models were successfully developed, which can accurately predict ΔGNO3 using the HEA structures as the input features. Through the analysis of the feature importance, it was found that the active sites are crucial for nitrate adsorption; meanwhile, the local environments also play a considerable role. The dependence of the ΔGNO3 and adsorption geometries on the HEA compositions demonstrates that the compositional modulation of the HEA catalysts could be a promising avenue for facile adsorption and activation of reaction intermediates. Overall, this work will contribute to the probabilistic optimization of the HEA microstructures for enhanced electrochemical nitrate reduction.
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AIMS AND OBJECTIVES: The main aim of this study is to synthesize the prevalent predictive models for pressure injuries in hospitalized patients, with the goal of identifying common predictive factors linked to pressure injuries in hospitalized patients. This endeavour holds the potential to provide clinical nurses with a valuable reference for providing targeted care to high-risk patients. BACKGROUND: Pressure injuries (PIs) are a frequently occurring health problem throughout the world. There are mounting studies about risk prediction model of PIs reported and published. However, the prediction performance of the models is still unclear. DESIGN: Systematic review and meta-analysis: The Cochrane Library, PubMed, Embase, CINAHL, Web of Science and Chinese databases including CNKI (China National Knowledge Infrastructure), Wanfang Database, Weipu Database and CBM (China Biology Medicine). METHODS: This systematic review was conducted following PRISMA recommendations. The databases of Cochrane Library, PubMed, Embase, CINAHL, Web of Science, and CNKI, Weipu Database, Wanfang Database and CBM were searched for all studies published before September 2023. We included studies with cohort, case-control designs, reporting the development of risk model and have been validated externally and internally among the hospitalized patients. Two researchers selected the retrieved studies according to the inclusion and exclusion criteria, and critically evaluated the quality of studies based on the CHARMS checklist. The PRISMA guideline was used to report the systematic review and meta-analysis. RESULTS: Sixty-two studies were included, which contained 99 pressure injuries risk prediction models. The AUC (area under ROC curve) of modelling in 32 prediction models were reported ranged from .70 to .99, while the AUC of verification in 38 models were reported ranged from .70 to .98. Gender (OR = 1.41, CI: .99 ~ 1.31), age (WMD = 8.81, CI: 8.11 ~ 9.57), diabetes mellitus (OR = 1.64, CI: 1.36 ~ 1.99), mechanical ventilation (OR = 2.71, CI: 2.05 ~ 3.57), length of hospital stay (WMD = 7.65, CI: 7.24 ~ 8.05) were the most common predictors of pressure injuries. CONCLUSION: Studies of PIs risk prediction model in hospitalized patients had high research quality, and the risk prediction models also had good predictive performance. However, some of the included studies lacked of internal or external validation in modelling, which affected the stability and extendibility. The aged, male patient in ICU, albumin, haematocrit, low haemoglobin level, diabetes, mechanical ventilation and length of stay in hospital were high-risk factors for pressure injuries in hospitalized patients. In the future, it is recommended that clinical nurses, in practice, select predictive models with better performance to identify high-risk patients based on the actual situation and provide care targeting the high-risk factors to prevent the occurrence of diseases. RELEVANCE TO CLINICAL PRACTICE: The risk prediction model is an effective tool for identifying patients at the risk of developing PIs. With the help of risk prediction tool, nurses can identify the high-risk patients and common predictive factors, predict the probability of developing PIs, then provide specific preventive measures to improve the outcomes of these patients. REGISTRATION NUMBER (PROSPERO): CRD42023445258.
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The indications for collagenase ointment (CO) and its efficacy are not clearly established in the treatment of second-degree burn wounds. To evaluate the efficacy of CO versus silver sulfadiazine ointment (SSD) in the treatment of second-degree burn wounds. A total of 170 eligible patients with deep second-degree burns, aged 18-65 years, with injuries occurring within 48-96 h, and having a total wound area of less than 30% of the total body surface area were included from 5 centers in China. The primary outcome was the wound healing time, and the secondary outcomes were the clearance time of wound necrotic tissues, wound healing rate, and wound inflammation. The study included 85 patients in SSD group and 84 in CO group in the modified intention-to-treat (mITT) population. The median time of wound healing was comparable in both groups (10 days vs. 10.5 days P = 0.16). The time for wound necrotic tissue removal was significantly shortened by CO compared with SSD (5 vs. 10 days P < 0.01). Wound inflammation, pain, wound healing rate, and scar were compared with SSD (all P-values > 0.05). No adverse events, such as infection or allergic reactions to the drugs and materials used, were reported. Both CO and SSD could heal the burn wounds at 10 days of treatment. However, CO significantly shortened the time of wound necrotic tissue removal by 5 days. Trial Registration: ChiCTR2100046971.
Subject(s)
Burns , Collagenases , Silver Sulfadiazine , Wound Healing , Humans , Silver Sulfadiazine/administration & dosage , Silver Sulfadiazine/therapeutic use , Burns/drug therapy , Adult , Middle Aged , Wound Healing/drug effects , Male , Female , Young Adult , Collagenases/administration & dosage , Adolescent , Treatment Outcome , Aged , Ointments/administration & dosage , Necrosis/drug therapy , China , Anti-Infective Agents, Local/administration & dosage , Anti-Infective Agents, Local/therapeutic use , Anti-Infective Agents, Local/adverse effectsABSTRACT
BACKGROUND: Traditional biopsies pose risks and may not accurately reflect soft tissue sarcoma (STS) heterogeneity. MRI provides a noninvasive, comprehensive alternative. PURPOSE: To assess the diagnostic accuracy of histological grading and prognosis in STS patients when integrating clinical-imaging parameters with deep learning (DL) features from preoperative MR images. STUDY TYPE: Retrospective/prospective. POPULATION: 354 pathologically confirmed STS patients (226 low-grade, 128 high-grade) from three hospitals and the Cancer Imaging Archive (TCIA), divided into training (n = 185), external test (n = 125), and TCIA cohorts (n = 44). 12 patients (6 low-grade, 6 high-grade) were enrolled into prospective validation cohort. FIELD STRENGTH/SEQUENCE: 1.5 T and 3.0 T/Unenhanced T1-weighted and fat-suppressed-T2-weighted. ASSESSMENT: DL features were extracted from MR images using a parallel ResNet-18 model to construct DL signature. Clinical-imaging characteristics included age, gender, tumor-node-metastasis stage and MRI semantic features (depth, number, heterogeneity at T1WI/FS-T2WI, necrosis, and peritumoral edema). Logistic regression analysis identified significant risk factors for the clinical model. A DL clinical-imaging signature (DLCS) was constructed by incorporating DL signature with risk factors, evaluated for risk stratification, and assessed for progression-free survival (PFS) in retrospective cohorts, with an average follow-up of 23 ± 22 months. STATISTICAL TESTS: Logistic regression, Cox regression, Kaplan-Meier curves, log-rank test, area under the receiver operating characteristic curve (AUC)ï¼and decision curve analysis. A P-value <0.05 was considered significant. RESULTS: The AUC values for DLCS in the external test, TCIA, and prospective test cohorts (0.834, 0.838, 0.819) were superior to clinical model (0.662, 0.685, 0.694). Decision curve analysis showed that the DLCS model provided greater clinical net benefit over the DL and clinical models. Also, the DLCS model was able to risk-stratify patients and assess PFS. DATA CONCLUSION: The DLCS exhibited strong capabilities in histological grading and prognosis assessment for STS patients, and may have potential to aid in the formulation of personalized treatment plans. TECHNICAL EFFICACY: Stage 2.
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Background: Lower respiratory tract infections represent prevalent ailments. Nonetheless, current comprehension of the microbial ecosystems within the lower respiratory tract remains incomplete and necessitates further comprehensive assessment. Leveraging the advancements in metagenomic next-generation sequencing (mNGS) technology alongside the emergence of machine learning, it is now viable to compare the attributes of lower respiratory tract microbial communities among patients across diverse age groups, diseases, and infection types. Method: We collected bronchoalveolar lavage fluid samples from 138 patients diagnosed with lower respiratory tract infections and conducted mNGS to characterize the lung microbiota. Employing various machine learning algorithms, we investigated the correlation of key bacteria in patients with concurrent bronchiectasis and developed a predictive model for hospitalization duration based on these identified key bacteria. Result: We observed variations in microbial communities across different age groups, diseases, and infection types. In the elderly group, Pseudomonas aeruginosa exhibited the highest relative abundance, followed by Corynebacterium striatum and Acinetobacter baumannii. Methylobacterium and Prevotella emerged as the dominant genera at the genus level in the younger group, while Mycobacterium tuberculosis and Haemophilus influenzae were prevalent species. Within the bronchiectasis group, dominant bacteria included Pseudomonas aeruginosa, Haemophilus influenzae, and Klebsiella pneumoniae. Significant differences in the presence of Pseudomonas phage JBD93 were noted between the bronchiectasis group and the control group. In the group with concomitant fungal infections, the most abundant genera were Acinetobacter and Pseudomonas, with Acinetobacter baumannii and Pseudomonas aeruginosa as the predominant species. Notable differences were observed in the presence of Human gammaherpesvirus 4, Human betaherpesvirus 5, Candida albicans, Aspergillus oryzae, and Aspergillus fumigatus between the group with concomitant fungal infections and the bacterial group. Machine learning algorithms were utilized to select bacteria and clinical indicators associated with hospitalization duration, confirming the excellent performance of bacteria in predicting hospitalization time. Conclusion: Our study provided a comprehensive description of the microbial characteristics among patients with lower respiratory tract infections, offering insights from various perspectives. Additionally, we investigated the advanced predictive capability of microbial community features in determining the hospitalization duration of these patients.
Subject(s)
Bacteria , Bronchoalveolar Lavage Fluid , High-Throughput Nucleotide Sequencing , Machine Learning , Metagenomics , Microbiota , Respiratory Tract Infections , Humans , Metagenomics/methods , Middle Aged , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/virology , Aged , Male , Female , Adult , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification , Bronchoalveolar Lavage Fluid/microbiology , Microbiota/genetics , Young Adult , Bronchiectasis/microbiology , Aged, 80 and over , Metagenome , Adolescent , Lung/microbiology , Lung/virology , HospitalizationABSTRACT
Hard carbon (HC) is one of the most promising anode materials for sodium-ion batteries (SIBs) due to its cost-effectiveness and low-voltage plateau capacity. Heteroatom doping is considered as an effective strategy to improve the sodium storage capacity of HC. However, most of the previous heteroatom doping strategies are performed at a relatively low temperature, which could not be utilized to raise the low-voltage plateau capacity. Moreover, extra doping of heteroatoms could create new defects, leading to a low initial coulombic efficiency (ICE). Herein, we propose a repair strategy based on doping a trace amount of P to achieve a high capacity along with a high ICE. By employing the cross-linked interaction between glucose and phytic acid to achieve the in situ P doped spherical hard carbon, the obtained PHC-0.2 possesses a large interlayer space that facilitates Na+ storage and transportation. In addition, doping a suitable amount of P could repair some defects in carbon layers. When used as an anode material for SIBs, the PHC-0.2 exhibits an enhanced reversible capacity of 343 mA h g-1 at 20 mA g-1 with a high ICE of 92%. Full cells consisting of a PHC-0.2 anode and a Na2Fe0.5Mn0.5[Fe(CN)6] cathode exhibited an average potential of 3.1 V with an initial discharge capacity of 255 mA h g-1 and an ICE of 85%. The full cell displays excellent cycling stability with a capacity retention of 80.3% after 170 cycles. This method is simple and low-cost, which can be extended to other energy storage materials.
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Adjuvants for vaccines with characteristics of improving adaptive immunity particularly via leverage of antigen presenting cells (APCs) are currently lacking. In a previous work we obtained a new soluble 300 kDa homogeneous ß-glucan named GFPBW1 from the fruit bodies of Granola frondosa. GFPBW1 could activate macrophages by targeting dendritic cell associated C-type lectin 1 (Dectin-1)/Syk/NF-κB signaling to achieve antitumour effects. In this study the adjuvant effects of GFPBW1 were explored with OVA-antigen and B16-OVA tumor model. We showed that GFPBW1 (5, 50, 500 µg/mL) dose-dependently promoted activation and maturation of APCs in vitro by increasing CD80, CD86 and MHC II expression. We immunized female mice with OVA in combination with GFPBW1 (50 or 300 µg) twice with an interval of two weeks. GFPBW1 markedly and dose-dependently increased OVA-specific antibody titers of different subtypes including IgG1, IgG2a, IgG2b and IgG3, suggesting that it could serve as an adjuvant for both Th1 and Th2 type immune responses. Furthermore, GFPBW1 in combination with aluminum significantly increased the titers of OVA-specific IgG2a and IgG2b, but not those of IgG1, suggesting that GFPBW1 could be used as a co-adjuvant of aluminum to compensate for Th1 deficiency. For mice immunized with OVA plus GFPBW1, no obvious pathological injury was observed in either major organs or injection sites, and no abnormalities were noted for any of the hematological parameters. When GFPBW1 served as an adjuvant in the B16-OVA cancer vaccine models, it could accomplish entire tumor suppression with preventive vaccines, and enhance antitumour efficacy with therapeutic vaccines. Differentially expressed genes were found to be enriched in antigen processing process, specifically increased tumor infiltration of DCs, B1 cells and plasma cells in the OVA plus GFPBW1 group, in accordance with its activation and maturation function of APCs. Collectively, this study systematically describes the properties of GFPBW1 as a novel potent and safe adjuvant and highlights its great potential in vaccine development.
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Acute myeloid leukemia (AML) with mixed-lineage leukemia (MLL) gene rearrangements (MLL-r) is an aggressive subtype of blood cancer with dismal prognosis, underscoring the urgent need for novel therapeutic strategies. E1A-binding protein (EP300) and CREB-binding protein (CREBBP) function as essential transcriptional coactivators and acetyltransferases, governing leukemogenesis through diverse mechanisms. Targeting EP300/CREBBP holds great promise for treating leukemia with some certain cytogenetic abnormalities. Here, we demonstrated that EP300 and CREBBP are core epigenetic regulators in the pathogenesis of MLL-r AML through assaying the transposase-accessible chromatin with high-throughput sequencing (ATAC-seq). Knocking-out EP300/CREBBP and inhibitor (A-485) treatment depressed the MLL-r cells proliferation, while the MLL wild-type cells remained uninfluenced. We found that the CDK4/RB/E2F axis was downregulated specifically in MLL-r AML cell after A-485 treatment by RNA-seq, western blot and cut-tag analyses. EP300/CREBBP inhibitor selectively exerted potent anti-leukemia activity through blocking the MLL-r-BET complex binding to H3K27Ac modification on critical genes loci, distinct from global histone acetylation. Collectively, our study identified EP300/CREBBP as a critical epigenetic driver of MLL-r leukemia and validated their therapeutic potential through targeting inhibition, offering a promising avenue for improving clinical outcomes in this aggressive leukemia.
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Designing molecules with donor-acceptor-donor (D-A-D) architecture plays an important role in obtaining second near-infrared region (NIR-II, 1000-1700 nm) fluorescent dyes for biomedical applications; however, this always comes with a challenge due to very limited electronic acceptors. On the other hand, to endow NIR-II fluorescent dyes with combined therapeutic applications, trivial molecular design is indispensable. Herein, we propose a pyrazine-based planar electronic acceptor with a strong electron affinity, which can be used to develop NIR-II fluorescent dyes. By structurally attaching two classical triphenylamine electronic donors to it, a basic D-A-D module, namely Py-NIR, can be generated. The planarity of the electronic acceptor is crucial to induce a distinct NIR-II emission peaking at â¼1100 nm. The unique construction of the electronic acceptor can cause a twisted and flexible molecular conformation by the repulsive effect between the donors, which is essential to the aggregation-induced emission (AIE) property. The tuned intramolecular motions and twisted D-A pair brought by the electronic acceptor can lead to a remarkable photothermal conversion with an efficiency of 56.1% and induce a type I photosensitization with a favorable hydroxyl radical (OHË) formation. Note that no additional measures are adopted in the molecular design, providing an ideal platform to realize NIR-II fluorescent probes with synergetic functions based on such an acceptor. Besides, the nanoparticles of Py-NIR can exhibit excellent NIR-II fluorescence imaging towards orthotopic 4T1 breast tumors in living mice with a high sensitivity and contrast. Combined with photothermal imaging and photoacoustic imaging caused by the thermal effect, the imaging-guided photoablation of tumors can be well performed. Our work has created a new opportunity to develop NIR-II fluorescent probes for accelerating biomedical applications.
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Objective. Magnetoencephalography (MEG) shares a comparable time resolution with electroencephalography. However, MEG excels in spatial resolution, enabling it to capture even the subtlest and weakest brain signals for brain-computer interfaces (BCIs). Leveraging MEG's capabilities, specifically with optically pumped magnetometers (OPM-MEG), proves to be a promising avenue for advancing MEG-BCIs, owing to its exceptional sensitivity and portability. This study harnesses the power of high-frequency steady-state visual evoked fields (SSVEFs) to build an MEG-BCI system that is flickering-imperceptible, user-friendly, and highly accurate.Approach.We have constructed a nine-command BCI that operates on high-frequency SSVEF (58-62 Hz with a 0.5 Hz interval) stimulation. We achieved this by placing the light source inside and outside the magnetic shielding room, ensuring compliance with non-magnetic and visual stimulus presentation requirements. Five participants took part in offline experiments, during which we collected six-channel multi-dimensional MEG signals along both the vertical (Z-axis) and tangential (Y-axis) components. Our approach leveraged the ensemble task-related component analysis algorithm for SSVEF identification and system performance evaluation.Main Results.The offline average accuracy of our proposed system reached an impressive 92.98% when considering multi-dimensional conjoint analysis using data from both theZandYaxes. Our method achieved a theoretical average information transfer rate (ITR) of 58.36 bits min-1with a data length of 0.7 s, and the highest individual ITR reached an impressive 63.75 bits min-1.Significance.This study marks the first exploration of high-frequency SSVEF-BCI based on OPM-MEG. These results underscore the potential and feasibility of MEG in detecting subtle brain signals, offering both theoretical insights and practical value in advancing the development and application of MEG in BCI systems.
Subject(s)
Brain-Computer Interfaces , Evoked Potentials, Visual , Magnetoencephalography , Photic Stimulation , Humans , Magnetoencephalography/methods , Evoked Potentials, Visual/physiology , Adult , Male , Female , Photic Stimulation/methods , Young Adult , Visual Cortex/physiologyABSTRACT
Photoadaptive synaptic devices enable in-sensor processing of complex illumination scenes, while second-order adaptive synaptic plasticity improves learning efficiency by modifying the learning rate in a given environment. The integration of above adaptations in one phototransistor device will provide opportunities for developing high-efficient machine vision system. Here, a dually adaptable organic heterojunction transistor as a working unit in the system, which facilitates precise contrast enhancement and improves convergence rate under harsh lighting conditions, is reported. The photoadaptive threshold sliding originates from the bidirectional photoconductivity caused by the light intensity-dependent photogating effect. Metaplasticity is successfully implemented owing to the combination of ambipolar behavior and charge trapping effect. By utilizing the transistor array in a machine vision system, the details and edges can be highlighted in the 0.4% low-contrast images, and a high recognition accuracy of 93.8% with a significantly promoted convergence rate by about 5 times are also achieved. These results open a strategy to fully implement metaplasticity in optoelectronic devices and suggest their vision processing applications in complex lighting scenes.