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1.
J Neurosci Methods ; 412: 110280, 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39271023

ABSTRACT

BACKGROUND: With the arrival of the new generation of artificial intelligence wave, new human-robot interaction technologies continue to emerge. Brain-computer interface (BCI) offers a pathway for state monitoring and interaction control between human and robot. However, the unstable mental state reduce the accuracy of human brain intent decoding, and consequently affects the precision of BCI control. NEW METHODS: This paper proposes a hybrid BCI-based shared control (HB-SC) method for brain-controlled robot navigation. Hybrid BCI fuses electroencephalogram (EEG) and electromyography (EMG) for mental state monitoring and interactive control to output human perception and decision. The shared control based on multi-sensory fusion integrates the special obstacle information perceived by humans with the regular environmental information perceived by the robot. In this process, valid BCI commands are screened by mental state assessment and output to a layered costmap for fusion. RESULTS: Eight subjects participated in the navigation experiment with dynamically changing mental state levels to validate the effects of a hybrid brain-computer interface through two shared control modes. The results show that the proposed HB-SC reduces collisions by 37.50 %, improves the success rate of traversing obstacles by 25.00 %, and the navigation trajectory is more consistent with expectations. CONCLUSIONS: The HB-SC method can dynamically and intelligently adjust command output according to different brain states, helping to reduce errors made by subjects in a unstable mental state, thereby greatly enhancing the system's safety.

2.
Polymers (Basel) ; 16(17)2024 Sep 02.
Article in English | MEDLINE | ID: mdl-39274134

ABSTRACT

Nitrile Butadiene Rubber (NBR) is widely used as a sealing material due to its excellent mechanical properties and good oil resistance. However, when using NBR material, the seal structure is unable to avoid the negative effects of rubber aging. Hence, the influence of oil and thermal aging on the characteristics of NBR seals was studied by coupling the mechanical behavioral changes with the tribological behavioral changes of NBR in oil and the thermal environment. For this paper, aging testing and compression testing of NBR were carried out. Additionally, friction testing between friction pairs under different aging times was carried out. The surface morphology of the NBR working surface under different aging conditions was also observed. Finally, coefficients of different test conditions were introduced into the finite element model of NBR seals. It can be seen from the results that the elastic modulus increased with the increase in aging time in the thermal oxidative aging testing. The elastic modulus after 7 days of thermal oxidative aging increased by 135.45% compared to the unaged case, and the elastic modulus after 7 days of oil aging increased by 15.03% compared to the unaged case. The compression set rate of NBR increased significantly with the increase in aging time and temperature. The coefficient of friction (COF) between friction pairs increased first and then decreased with the increase in aging time. The maximum contact pressure decreased by 2.43% between the shaft and sealing ring and decreased by 4.01% between the O-ring and groove. The proportion of the effective sealing area decreased by 3.05% between the shaft and sealing ring and decreased by 6.11% between the O-ring and groove. Furthermore, the sealing characteristics between the O-ring and groove were better than those between the shaft and sealing ring.

3.
Integr Zool ; 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39285583

ABSTRACT

The parent-offspring conflict in avian species encompasses resource allocation and a balance necessary for survival for both parties. Parental investment is modulated according to various factors, among which begging is important. Endogenous hormones, particularly corticosterone (CORT), play a role in modulating begging behavior. However, most studies on hormonal regulation of begging behavior induced elevated hormone levels in the offspring through feeding or injections, thus, limiting our knowledge of the evolution of the parent-offspring conflict under natural conditions. In this study, we aimed to identify the key signals that parents respond to during interactions with their nestlings in the wild, considering factors such as endogenous hormone CORT, nestling age, and brood size, which may affect nestling begging behavior. Begging performance was evaluated by measuring the begging frequency and score of the red-whiskered bulbul (Pycnonotus jocosus), along with assessing CORT levels in feathers. CORT levels were significantly correlated with both the begging frequency and score of nestlings, while variables such as body mass and tarsus length did not influence parental feeding frequency. Additionally, factors such as the number of nestlings (brood size), age, and begging frequency were predictors of parental feeding frequency. Our findings indicate that begging frequency, nestling age, and brood size are signals that help navigate the intricacies of the parent-offspring conflict and that parents may rely on these key signals from the range of begging cues exhibited by nestlings to adjust their feeding strategies.

4.
J Biomed Inform ; 157: 104718, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39209086

ABSTRACT

Radiology report generation automates diagnostic narrative synthesis from medical imaging data. Current report generation methods primarily employ knowledge graphs for image enhancement, neglecting the interpretability and guiding function of the knowledge graphs themselves. Additionally, few approaches leverage the stable modal alignment information from multimodal pre-trained models to facilitate the generation of radiology reports. We propose the Terms-Guided Radiology Report Generation (TGR), a simple and practical model for generating reports guided primarily by anatomical terms. Specifically, we utilize a dual-stream visual feature extraction module comprised of detail extraction module and a frozen multimodal pre-trained model to separately extract visual detail features and semantic features. Furthermore, a Visual Enhancement Module (VEM) is proposed to further enrich the visual features, thereby facilitating the generation of a list of anatomical terms. We integrate anatomical terms with image features and proceed to engage contrastive learning with frozen text embeddings, utilizing the stable feature space from these embeddings to boost modal alignment capabilities further. Our model incorporates the capability for manual input, enabling it to generate a list of organs for specifically focused abnormal areas or to produce more accurate single-sentence descriptions based on selected anatomical terms. Comprehensive experiments demonstrate the effectiveness of our method in report generation tasks, our TGR-S model reduces training parameters by 38.9% while performing comparably to current state-of-the-art models, and our TGR-B model exceeds the best baseline models across multiple metrics.


Subject(s)
Natural Language Processing , Humans , Radiology/education , Radiology/methods , Algorithms , Machine Learning , Semantics , Radiology Information Systems , Diagnostic Imaging/methods
5.
J Nanobiotechnology ; 22(1): 500, 2024 Aug 21.
Article in English | MEDLINE | ID: mdl-39169401

ABSTRACT

Bone defects pose significant challenges in healthcare, with over 2 million bone repair surgeries performed globally each year. As a burgeoning force in the field of bone tissue engineering, 3D printing offers novel solutions to traditional bone transplantation procedures. However, current 3D-printed bone scaffolds still face three critical challenges in material selection, printing methods, cellular self-organization and co-culture, significantly impeding their clinical application. In this comprehensive review, we delve into the performance criteria that ideal bone scaffolds should possess, with a particular focus on the three core challenges faced by 3D printing technology during clinical translation. We summarize the latest advancements in non-traditional materials and advanced printing techniques, emphasizing the importance of integrating organ-like technologies with bioprinting. This combined approach enables more precise simulation of natural tissue structure and function. Our aim in writing this review is to propose effective strategies to address these challenges and promote the clinical translation of 3D-printed scaffolds for bone defect treatment.


Subject(s)
Bioprinting , Bone and Bones , Organoids , Printing, Three-Dimensional , Tissue Engineering , Tissue Scaffolds , Tissue Scaffolds/chemistry , Humans , Tissue Engineering/methods , Organoids/cytology , Bioprinting/methods , Animals , Bone Regeneration , Bone Transplantation/methods
6.
ACS Sens ; 9(8): 4196-4206, 2024 Aug 23.
Article in English | MEDLINE | ID: mdl-39096304

ABSTRACT

Reliable and real-time monitoring of seafood decay is attracting growing interest for food safety and human health, while it is still a great challenge to accurately identify the released triethylamine (TEA) from the complex volatilome. Herein, defect-engineered WO3-x architectures are presented to design advanced TEA sensors for seafood quality assessment. Benefiting from abundant oxygen vacancies, the obtained WO2.91 sensor exhibits remarkable TEA-sensing performance in terms of higher response (1.9 times), faster response time (2.1 times), lower detection limit (3.2 times), and higher TEA/NH3 selectivity (2.8 times) compared with the air-annealed WO2.96 sensor. Furthermore, the definite WO2.91 sensor demonstrates long-term stability and anti-interference in complex gases, enabling the accurate recognition of TEA during halibut decay (0-48 h). Coupled with the random forest algorithm with 70 estimators, the WO2.91 sensor enables accurate prediction of halibut storage with an accuracy of 95%. This work not only provides deep insights into improving gas-sensing performance by defect engineering but also offers a rational solution for reliably assessing seafood quality.


Subject(s)
Algorithms , Oxides , Seafood , Tungsten , Seafood/analysis , Tungsten/chemistry , Oxides/chemistry , Food Quality , Random Forest
7.
Cell Mol Immunol ; 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39164536

ABSTRACT

The preferable antigen delivery profile accompanied by sufficient adjuvants favors vaccine efficiency. Mitochondria, which feature prokaryotic characteristics and contain various damage-associated molecular patterns (DAMPs), are easily taken up by phagocytes and simultaneously activate innate immunity. In the current study, we established a mitochondria engineering platform for generating antigen-enriched mitochondria as cancer vaccine. Ovalbumin (OVA) and tyrosinase-related protein 2 (TRP2) were used as model antigens to synthesize fusion proteins with mitochondria-localized signal peptides. The lentiviral infection system was then employed to produce mitochondrial vaccines containing either OVA or TRP2. Engineered OVA- and TRP2-containing mitochondria (OVA-MITO and TRP2-MITO) were extracted and evaluated as potential cancer vaccines. Impressively, the engineered mitochondria vaccine demonstrated efficient antitumor effects when used as both prophylactic and therapeutic vaccines in murine tumor models. Mechanistically, OVA-MITO and TRP2-MITO potently recruited and activated dendritic cells (DCs) and induced a tumor-specific cell-mediated immunity. Moreover, DC activation by mitochondria vaccine critically involves TLR2 pathway and its lipid agonist, namely, cardiolipin derived from the mitochondrial membrane. The results demonstrated that engineered mitochondria are natively well-orchestrated carriers full of immune stimulants for antigen delivery, which could preferably target local dendritic cells and exert strong adaptive cellular immunity. This proof-of-concept study established a universal platform for vaccine construction with engineered mitochondria bearing alterable antigens for cancers as well as other diseases.

8.
ACS Nano ; 18(36): 24953-24967, 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39197151

ABSTRACT

Strengthening tumor cellular adhesion through regulating the concentration of extracellular Ca2+ is highly challenging and promising for antimetastasis. Herein, a pH-responsive conjugated polymer-calcium composite nanoparticle (PFV/CaCO3/PDA@PEG) is developed for calcium-mediated cell adhesion enhancement-based antimetastasis and reactive oxygen species (ROS)-triggered calcium overload and photodynamic therapy (PDT) synergistic tumor treatment. PFV/CaCO3/PDA@PEG is mainly equipped with conjugated poly(fluorene-co-vinylene) (PFV-COOH)-composited CaCO3 nanoparticles, which can be rapidly decomposed under the tumor acidic microenvironment, effectively releasing Ca2+ and the photosensitizer PFV-COOH. The high extracellular Ca2+ concentration facilitates the generation of dimers between two adjacent cadherin ectodomains, which greatly enhances cell-cell adhesion and suppresses tumor metastasis. The inhibition rates are 97 and 87% for highly metastatic tumor cells 4T1 and MCF-7, respectively. Such a well-designed nanoparticle also contributes to realizing PDT, mitochondrial dysfunction, and ROS-triggered Ca2+ overload synergistic therapy. Furthermore, PFV/CaCO3/PDA@PEG displayed superior in vivo inhibition of 4T1 tumor growth and demonstrated a marked antimetastatic effect by both intravenous and intratumoral injection modes. Thus, this study provides a powerful strategy for calcium-mediated metastasis inhibition for tumor therapy.


Subject(s)
Antineoplastic Agents , Calcium , Cell Adhesion , Nanoparticles , Photochemotherapy , Reactive Oxygen Species , Nanoparticles/chemistry , Humans , Animals , Calcium/metabolism , Cell Adhesion/drug effects , Mice , Reactive Oxygen Species/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Polymers/chemistry , Polymers/pharmacology , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemistry , Female , Mice, Inbred BALB C , MCF-7 Cells , Calcium Carbonate/chemistry , Calcium Carbonate/pharmacology , Cell Proliferation/drug effects , Neoplasm Metastasis , Cell Line, Tumor , Drug Screening Assays, Antitumor
9.
J Vasc Interv Radiol ; 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39208929

ABSTRACT

PURPOSE: To develop and compare three different machine learning-based models of clinical information and integrated radiomics features predicting the local recurrence of stage Ia lung adenocarcinoma after microwave ablation (MWA) for assisting clinical decision-making. MATERIALS AND METHODS: The data of 360 patients with stage Ia lung adenocarcinoma receiving MWA were included in the training (n = 208), internal test (n = 90), and external test (n = 64) sets based on the inclusion and exclusion criteria. The predictors associated with local recurrence were identified using univariate and multivariate analyses of clinical information. The integrated radiomics features were extracted from pre-MWA and post-MWA (scanned immediately after the ablation) CT images, and ten radiomics features were selected by the t-test and least absolute shrinkage and selection operator (LASSO). The L2-logistic regression of machine learning was applied for the clinical model, CT radiomics model and combined model including clinical predictors and radiomics features. Model performance was evaluated by the receiver operating characteristic (ROC) and decision curve analysis (DCA). RESULTS: The ablative margin was an independent clinical predictor (p = 0.001, odds ratio [OR] = 0.46, 95%CI: 0.29, 0.73). The combined model showed the highest area under the curve (AUC) value among the three models (training: 0.86, 95%CI: 0.81, 0.91; internal test: 0.93, 95%CI: 0.87, 0.98; external test: 0.89, 95%CI: 0.79, 0.96). CONCLUSION: The combined model could accurately predict the local recurrence of stage Ia lung adenocarcinoma after MWA to better support a clinical decision.

10.
Front Endocrinol (Lausanne) ; 15: 1364280, 2024.
Article in English | MEDLINE | ID: mdl-39157683

ABSTRACT

Background: Gut microbiota (GM) homeostasis in the human body is closely associated with health, which can be used as a regulator for preventing the onset and progression of disease. Diabetic microvascular complications bring about not only a huge economic burden to society, but also miserable mental and physical pain. Thus, alteration of the GM may be a method to delay diabetic microvascular complications. Objective: A two-sample Mendelian randomization (MR) analysis was conducted to reveal the causal inference between GM and three core diabetic microvascular complications, namely, diabetic kidney disease (DKD), diabetic retinopathy (DR), and diabetic neuropathy (DNP). Methods: First, genome-wide association study (GWAS) summary statistics for GM from the MiBioGen consortium and three main diabetic microvascular complications acquired from the FinnGen research project were assessed. Second, a forward MR analysis was conducted to assess the causality of GM on the risk of DKD, DR, and DNP. Third, a series of sensitivity studies, such as heterogeneity tests, pleiotropy evaluations, and leave-one-out analyses, were further conducted to assess the accuracy of MR analysis. Finally, Steiger tests and reverse MR analyses were performed to appraise the possibility of reverse causation. Results: A total of 2,092 single-nucleotide polymorphisms related to 196 bacterial traits were selected as instrumental variables. This two-sample MR analysis provided strongly reasonable evidence that 28 genetically predicted abundance of specific GM that played non-negligible roles in the occurrence of DKD, DR, and DNP complications were causally associated with 23 GM, the odds ratio of which generally ranged from 0.9 to 1.1. Further sensitivity analysis indicated low heterogeneity, low pleiotropy, and high reliability of the causal estimates. Conclusion: The study raised the possibility that GM may be a potential target to prevent and delay the progression of diabetic microvascular complications. Further experiments of GM therapy on diabetic microvascular complications are warranted to clarify their effects and specific mechanisms.


Subject(s)
Diabetic Angiopathies , Gastrointestinal Microbiome , Genome-Wide Association Study , Mendelian Randomization Analysis , Humans , Gastrointestinal Microbiome/genetics , Diabetic Angiopathies/genetics , Diabetic Angiopathies/microbiology , Diabetic Nephropathies/genetics , Diabetic Nephropathies/microbiology , Polymorphism, Single Nucleotide , Diabetic Neuropathies/genetics , Diabetic Neuropathies/microbiology , Diabetic Neuropathies/etiology , Diabetic Retinopathy/genetics , Diabetic Retinopathy/microbiology , Diabetic Retinopathy/etiology
11.
Microsyst Nanoeng ; 10: 110, 2024.
Article in English | MEDLINE | ID: mdl-39145147

ABSTRACT

AlGaN-based light-emitting diodes (LEDs) operating in the deep-ultraviolet (DUV) spectral range (210-280 nm) have demonstrated potential applications in physical sterilization. However, the poor external quantum efficiency (EQE) hinders further advances in the emission performance of AlGaN-based DUV LEDs. Here, we demonstrate the performance of 270-nm AlGaN-based DUV LEDs beyond the state-of-the-art by exploiting the innovative combination of bandgap engineering and device craft. By adopting tailored multiple quantum wells (MQWs), a reflective Al reflector, a low-optical-loss tunneling junction (TJ) and a dielectric SiO2 insertion structure (IS-SiO2), outstanding light output powers (LOPs) of 140.1 mW are achieved in our DUV LEDs at 850 mA. The EQEs of our DUV LEDs are 4.5 times greater than those of their conventional counterparts. This comprehensive approach overcomes the major difficulties commonly faced in the pursuit of high-performance AlGaN-based DUV LEDs, such as strong quantum-confined Stark effect (QCSE), severe optical absorption in the p-electrode/ohmic contact layer and poor transverse magnetic (TM)-polarized light extraction. Furthermore, the on-wafer electroluminescence characterization validated the scalability of our DUV LEDs to larger production scales. Our work is promising for the development of highly efficient AlGaN-based DUV LEDs.

12.
J Cell Physiol ; : e31393, 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39210747

ABSTRACT

AMP-activated protein kinase (AMPK), a crucial regulatory kinase, monitors energy levels, conserving ATP and boosting synthesis in low-nutrition, low-energy states. Its sensitivity links microenvironmental changes to cellular responses. As the primary support structure and endocrine organ, the maintenance, and repair of bones are closely associated with the microenvironment. While a series of studies have explored the effects of specific microenvironments on bone, there is lack of angles to comprehensively evaluate the interactions between microenvironment and bone cells, especially for bone marrow mesenchymal stem cells (BMMSCs) which mediate the differentiation of osteogenic lineage. It is noteworthy that accumulating evidence has indicated that AMPK may serve as a hub between BMMSCs and microenvironment factors, thus providing a new perspective for us to understand the biology and pathophysiology of stem cells and bone. In this review, we emphasize AMPK's pivotal role in bone microenvironment modulation via ATP, inflammation, reactive oxygen species (ROS), calcium, and glucose, particularly in BMMSCs. We further explore the use of AMPK-activating drugs in the context of osteoarthritis and osteoporosis. Moreover, building upon the foundation of AMPK, we elucidate a viewpoint that facilitates a comprehensive understanding of the dynamic relationship between the microenvironment and bone homeostasis, offering valuable insights for prospective investigations into stem cell biology and the treatment of bone diseases.

13.
Drug Metab Dispos ; 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39214663

ABSTRACT

Organic anion transporting polypeptides (OATP, gene symbol SLCO) are well-recognized key determinants for the absorption, distribution, and excretion of a wide spectrum of endogenous and exogenous compounds including many antineoplastic agents. It was therefore proposed as a potential drug target for cancer therapy. In our previous study, it was found that low-dose X-ray and carbon ion irradiation both up-regulated the expression of OATP family member OATP1A2 and in turn, led to a more dramatic killing effect when cancer cells were co-treated with antitumor drugs such as methotrexate. In the present study, the underlying mechanism of the phenomenon was explored in breast cancer cell line MCF-7. It was found that the non-receptor tyrosine kinase YES-1 was temporally coordinated with the change of OATP1A2 after irradiation. The over-expression of YES-1 significantly increased OATP1A2 both at the mRNA and protein level. The signal transducer and activator of transcription 3 (STAT3) pathway is likely the downstream target of YES-1 since phosphorylation and nuclear accumulation of STAT3 were both enhanced after over-expressing YES-1 in MCF-7 cells. Further investigation revealed that there are two possible binding sites of STAT3 localized at the upstream sequence of SLCO1A2, the encoding gene of OATP1A2. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) analysis suggested that these two sites bound to STAT3 specifically and the over-expression of YES-1 significantly increased the association of the transcription factor with the putative binding sites. Finally, inhibition or knock-down of YES-1 attenuated the induction effect of radiation on the expression of OATP1A2. Significance Statement The current study found that the effect of X-rays on YES-1 and OATP1A2 is temporally coordinated. YES-1 phosphorylates and increases the nuclear accumulation of STAT3, which in turn binds to the upstream regulatory sequences of SLCO1A2, the coding gene for OATP1A2. Hence, inhibitors of YES-1 may suppress the radiation induction effect on OATP1A2.

14.
Nanoscale ; 16(30): 14469-14476, 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39016026

ABSTRACT

Semitransparent perovskite solar cells (ST-PSCs) have great potential in building integrated photovoltaics. However, semitransparent devices suffer from a low electron mobility and an imbalanced charge-carrier transport, leading to an unsatisfactory power conversion efficiency (PCE) and limited stability. Herein, we report a high-performance ST-PSC via the incorporation of a special Lewis base. A better perovskite with an improved crystallinity and less defects was achieved, and a matched energy level alignment between the perovskite and [6,6]-phenyl-C61-butyric acid methyl ester was also induced, thereby leading to a high electron mobility and an exceptional balance of hole and electron mobility approaching 1 : 1. The prepared ST-PSC exhibited a PCE of 20.22% at average visible transmittance (AVT) of 4.93%, 18.32% at AVT of 14.38%, and 15.00% at AVT of 25.65%. These PCEs are the highest values among those ST-PSCs based on top metallic electrodes at a close AVT. The ST-PSCs maintained 92% of the initial PCE in storage for 1000 h, and they held 84% of the initial PCE under the continuous maximum power point tracking measurement for 530 hours. The work paves the way to realize ST-PSCs with a high PCE, high light utilization efficiency and substantially enhanced stability.

15.
Int J Biol Sci ; 20(9): 3480-3496, 2024.
Article in English | MEDLINE | ID: mdl-38993560

ABSTRACT

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of chronic liver-related morbidity and mortality. Though high fructose intake is acknowledged as a metabolic hazard, its role in the etiology of MASLD requires further clarification. Here, we demonstrated that high dietary fructose drives MASLD development and promotes MASLD progression in mice, and identified Usp2 as a fructose-responsive gene in the liver. Elevated USP2 levels were detected in the hepatocytes of MASLD mice; a similar increase was observed following fructose exposure in primary hepatocytes and mouse AML12 cells. Notably, hepatocytes overexpressing USP2 presented with exaggerated lipid accumulation and metabolic inflammation when exposed to fructose. Conversely, USP2 knockdown mitigated these fructose-induced changes. Furthermore, USP2 was found to activate the C/EBPα/11ß-HSD1 signaling, which further impacted the equilibrium of cortisol and cortisone in the circulation of mice. Collectively, our findings revealed the role of dietary fructose in MASLD pathogenesis and identified the USP2-mediated C/EBPα/ 11ß-HSD1 signaling as a potential target for the management of MASLD.


Subject(s)
11-beta-Hydroxysteroid Dehydrogenase Type 1 , Fructose , Ubiquitin Thiolesterase , Animals , Mice , Fructose/adverse effects , Ubiquitin Thiolesterase/metabolism , Ubiquitin Thiolesterase/genetics , Male , 11-beta-Hydroxysteroid Dehydrogenase Type 1/metabolism , 11-beta-Hydroxysteroid Dehydrogenase Type 1/genetics , Mice, Inbred C57BL , Signal Transduction , Fatty Liver/metabolism , Hepatocytes/metabolism , Liver/metabolism , Endopeptidases/metabolism
16.
Food Funct ; 15(15): 8116-8127, 2024 Jul 29.
Article in English | MEDLINE | ID: mdl-39011610

ABSTRACT

Research on plant and animal peptides has garnered significant attention, but there is a lack of studies on the functional properties of Tenebrio molitor peptides, particularly in relation to their potential mitigating effect on radiation damage and the underlying mechanisms. This study aims to explore the protective effects of Tenebrio molitor peptides against radiation-induced damage. Mice were divided into five groups: normal, radiation model, and low-, medium-, and high-dose Tenebrio molitor peptide (TMP) groups (0.15 g per kg BW, 0.30 g per kg BW, and 0.60 g per kg BW). Various parameters such as blood cell counts, bone marrow DNA content, immune organ indices, serum levels of D-lactic acid, diamine oxidase (DAO), endotoxin (LPS), and inflammatory factors were assessed at 3 and 15 days post gamma irradiation. Additionally, the intestinal tissue morphology was examined through H&E staining, RT-qPCR experiments were conducted to analyze the expression of inflammatory factors in the intestine, and immunohistochemistry was utilized to evaluate the expression of tight junction proteins ZO-1 and Occludin in the intestine. The findings revealed that high-dose TMP significantly enhanced the hematopoietic system function in mice post radiation exposure, leading to increased spleen index, thymus index, blood cell counts, and bone marrow DNA production (p < 0.05). Moreover, TMP improved the intestinal barrier integrity and reduced the intestinal permeability. Mechanistic insights suggested that these peptides may safeguard intestinal barrier function by downregulating the gene expression of inflammatory factors TNF-α, IL-1ß, and IL-6, while upregulating the expression of tight junction proteins ZO-1 and Occludin (p < 0.05). Overall, supplementation with TMP mitigates radiation-induced intestinal damage by enhancing the hematopoietic system and the intestinal barrier, offering valuable insights for further investigations into the mechanisms underlying the protective effects of these peptides against ionizing radiation.


Subject(s)
Intestinal Mucosa , Peptides , Tenebrio , Animals , Mice , Peptides/pharmacology , Intestinal Mucosa/metabolism , Intestinal Mucosa/radiation effects , Intestinal Mucosa/drug effects , Male , Hematopoietic System/drug effects , Hematopoietic System/radiation effects , Radiation-Protective Agents/pharmacology , Zonula Occludens-1 Protein/metabolism , Zonula Occludens-1 Protein/genetics , Gamma Rays/adverse effects , Occludin/metabolism , Occludin/genetics , Intestines/drug effects , Intestines/radiation effects
17.
Structure ; 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38968938

ABSTRACT

Contactin 2 (CNTN2) is a cell adhesion molecule involved in axon guidance, neuronal migration, and fasciculation. The ectodomains of CNTN1-CNTN6 are composed of six Ig domains (Ig1-Ig6) and four FN domains. Here, we show that CNTN2 forms transient homophilic interactions (KD ∼200 nM). Cryo-EM structures of full-length CNTN2 and CNTN2_Ig1-Ig6 reveal a T-shaped homodimer formed by intertwined, parallel monomers. Unexpectedly, the horseshoe-shaped Ig1-Ig4 headpieces extend their Ig2-Ig3 tips outwards on either side of the homodimer, while Ig4, Ig5, Ig6, and the FN domains form a central stalk. Cross-linking mass spectrometry and cell-based binding assays confirm the 3D assembly of the CNTN2 homodimer. The interface mediating homodimer formation differs between CNTNs, as do the homophilic versus heterophilic interaction mechanisms. The CNTN family thus encodes a versatile molecular platform that supports a very diverse portfolio of protein interactions and that can be leveraged to strategically guide neural circuit development.

18.
ACS Nano ; 18(29): 19190-19199, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-38989607

ABSTRACT

Lewis base molecules bind the undercoordinated lead atoms at interfaces and grain boundaries, leading to the high efficiency and stability of flexible perovskite solar cells (PSCs). We demonstrated a highly efficient, stable, and flexible PSC via interface passivation using a Lewis base of tri(o-tolyl)phosphine (TTP). It not only induced an intimate interface contact and a complete deposition of the perovskite thin layers on hole transport layers (HTLs) but also led to a better perovskite with a raised crystallinity, fewer defects, and a better morphology, including fewer gullies, high uniformity, and low roughness. Furthermore, the TTP treatments induced a good alignment of energy levels among the perovskites, HTLs, and C60. The resultant flexible inverted PSCs exhibited a high power conversion efficiency (PCE) of 23.81%, which is one of the highest PCEs among these flexible inverted PSCs. Moreover, the optimized flexible PSCs exhibited high storage stability, superior operation stability, and enhanced mechanical flexibility. This study presents an effective method to substantially raise the PCE, stability, and mechanical flexibility of the flexible inverted perovskite photovoltaics.

19.
Angew Chem Int Ed Engl ; 63(37): e202410417, 2024 Sep 09.
Article in English | MEDLINE | ID: mdl-38924241

ABSTRACT

The electrochemical production of hydrogen peroxide (H2O2) using metal-free catalysts has emerged as a viable and sustainable alternative to the conventional anthraquinone process. However, the precise architectural design of these electrocatalysts poses a significant challenge, requiring intricate structural engineering to optimize electron transfer during the oxygen reduction reaction (ORR). Herein, we introduce a novel design of covalent organic frameworks (COFs) that effectively shift the ORR from a four-electron to a more advantageous two-electron pathway. Notably, the JUC-660 COF, with strategically charge-modified benzyl moieties, achieved a continuous high H2O2 yield of over 1200 mmol g-1 h-1 for an impressive duration of over 85 hours in a flow cell setting, marking it as one of the most efficient metal-free and non-pyrolyzed H2O2 electrocatalysts reported to date. Theoretical computations alongside in situ infrared spectroscopy indicate that JUC-660 markedly diminishes the adsorption of the OOH* intermediate, thereby steering the ORR towards the desired pathway. Furthermore, the versatility of JUC-660 was demonstrated through its application in the electro-Fenton reaction, where it efficiently and rapidly removed aqueous contaminants. This work delineates a pioneering approach to altering the ORR pathway, ultimately paving the way for the development of highly effective metal-free H2O2 electrocatalysts.

20.
Article in English | MEDLINE | ID: mdl-38910166

ABSTRACT

BACKGROUND: The aim of the present study was to develop a novel 64Cu-labeled cyclic peptide ([64Cu]Cu-FAP-NOX) that targets fibroblast activation protein (FAP) and may offer advantages in terms of image contrast, imaging time window, and low uptake in normal tissues. METHODS: The novel cyclic peptide featuring with a N-oxalyl modified tail was constructed and conjugated to NOTA for 64Cu labeling. Biochemical and cellular assays were performed with A549.hFAP cells. The performance of [64Cu]Cu-FAP-NOX was compared to that of two established tracers ([64Cu]Cu-FAPI-04 and [68Ga]Ga-FAP-2286) and three different NOTA-conjugates in HEK-293T.hFAP xenograft mice using micro-PET imaging. Ex vivo biodistribution studies were performed to confirm the FAP specificity and to validate the PET data. Furthermore, a first-in-human study of this novel tracer was conducted on one patient with lung cancer. RESULTS: Compared to [64Cu]Cu-FAPI-04, [64Cu]Cu-FAP-NOX demonstrated faster and higher rates of cellular uptake and internalization in A549.hFAP cells, but lower rates of cellular efflux. All six radiotracers were rapidly taken up by the tumor within the first 4 h post-injection. However, [64Cu]Cu-FAP-NOX had more intense tumor accumulation and slower washout from the target. The ratios of the tumor to normal tissue (including kidneys and muscles) increased significantly over time, with [64Cu]Cu-FAP-NOX reaching the highest ratio among all tracers. In the patient, [64Cu]Cu-FAP-NOX PET showed a comparable result to FDG PET in the primary malignant lesion while exhibiting higher uptake in pleural metastases, consistent with elevated FAP expression as confirmed by immunohistochemistry. CONCLUSION: [64Cu]Cu-FAP-NOX is a promising FAP-targeted tracer with a highly flexible imaging time window, as evidenced by preclinical evaluation encompassing biodistribution and micro-PET studies, along with a successful patient application. Furthermore, [64Cu]Cu-FAP-NOX showed enhanced image contrast and favorable pharmacokinetic properties for FAP PET imaging, warranting translation into large cohort studies.

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