ABSTRACT
In this study, peptides designed using fragments of an antifreeze protein (AFP) from the freeze-tolerant insect Tenebrio molitor, TmAFP, were evaluated as inhibitors of clathrate hydrate formation. It was found that these peptides exhibit inhibitory effects by both direct and indirect mechanisms. The direct mechanism involves the displacement of methane molecules by hydrophobic methyl groups from threonine residues, preventing their diffusion to the hydrate surface. The indirect mechanism is characterized by the formation of cylindrical gas bubbles, the morphology of which reduces the pressure difference at the bubble interface, thereby slowing methane transport. The transfer of methane to the hydrate interface is primarily dominated by gas bubbles in the presence of antifreeze peptides. Spherical bubbles facilitate methane migration and potentially accelerate hydrate formation; conversely, the promotion of a cylindrical bubble morphology by two of the designed systems was found to mitigate this effect, leading to slower methane transport and reduced hydrate growth. These findings provide valuable guidance for the design of effective peptide-based inhibitors of natural-gas hydrate formation with potential applications in the energy and environmental sectors.
Subject(s)
Antifreeze Proteins , Methane , Tenebrio , Water , Antifreeze Proteins/chemistry , Kinetics , Methane/chemistry , Methane/analogs & derivatives , Water/chemistry , Tenebrio/chemistry , Animals , Gases/chemistry , Peptides/chemistry , Peptides/pharmacologyABSTRACT
An important concern is the availability of clean drinking water, which is an essential need for human survival. This issue arises due to the existence of hazardous micropollutants originating from various emission sources. Nanotechnology aids in the mitigation of micropollutants by assimilating and counteracting their effects, hence diminishing their influence on water and other ecosystems. The study investigates the relationship between nanotechnological progress, the adoption of renewable energy, environmental consequences, and economic growth in China, using the Environmental Kuznets Curve theory as a conceptual framework. The study employs panel cointegration tests to analyze structural breaks from 2000 to 2020. Nanotechnology is expected to reduce environmental degradation and the presence of micro-pollutants by increasing the use of renewable energy and promoting energy conservation. Nanotechnology is crucial for mitigating micro-pollutants and advancing sustainable development in this specific context. However, the literature also highlights the harmful consequences of nanoparticle emissions caused by nanotechnology on human and environmental health for a long duration, requiring more examination. This research is the first empirical inquiry into the relationship between improvements in nanotechnology, the use of renewable energy, economic growth, and ecological effect, all within the context of the Environmental Kuznets Curve theory. The results confirm the successful incorporation of all components with a focus on long-term outcomes. The findings suggest that the EKC hypothesis is relevant in China. In China, advancements in nanotechnology have a moderating effect on environmental degradation. The use of renewable energy sources in China enhances environmental circumstances. Given the offered empirical evidence, it is advisable for the government to have a leading role in the development of innovative nanotechnologies that have low emissions of nanoparticles. By using this approach, it will be possible to encourage the conservation of energy and the use of renewable sources in a more secure way, hence improving the effectiveness of sustainable development initiatives.
Subject(s)
Economic Development , Nanotechnology , Renewable Energy , China , Humans , Environmental Pollutants , Ecosystem , Environmental Monitoring/methodsABSTRACT
Innovative products entering the market will cause dynamic changes in market demand, and consumers' purchase regret and their return behavior make the market environment more and more complex, which in turn affects the dynamic decision-making in the supply chain. In this paper, under the situation of discrete decision time, combining with the objective reality, we make discrete modification to the classical Bass diffusion model (Bass model), construct a manufacturer-led, retailer-followed supply chain differential game model, analyze the optimal decision-making of the manufacturer and the retailer by combining with the theory of discrete optimal control, and then verify the conclusions by numerical simulation. The results show that: when retailers purchase directly from the manufacturer and sell in the market, the optimal pricing of the innovative product can make the supply chain as a whole, realizing Pareto optimality; consumer's purchase regret will increase the amount of returns, which will lead to the decrease of product sales and the profits of the manufacturer and the retailer; when the innovative product accounts for a different share of the market, the impact of purchase regret on the wholesale price and the retail price are also different. Therefore, manufacturers need to have an extensive comprehension of the market to minimize the negative effects of consumer regret and returns, and to formulate a reasonable pricing strategy for their products to gain as much profit as possible.
Subject(s)
Commerce , Consumer Behavior , Humans , Emotions , Models, Economic , Decision Making , Game TheoryABSTRACT
Postoperative rehemorrhage following intracerebral hemorrhage surgery is intricately associated with a high mortality rate, yet there is now no effective clinical treatment. In this study, we developed a hemoglobin (Hb)-responsive in situ implantable DNA hydrogel comprising Hb aptamers cross-linked with two complementary chains and encapsulating deferoxamine mesylate (DFO). Functionally, the hydrogel generates signals upon postoperative rehemorrhage by capturing Hb, demonstrating a distinctive "self-diagnosis" capability. In addition, the ongoing capture of Hb mediates the gradual disintegration of the hydrogel, enabling the on-demand release of DFO without compromising physiological iron-dependent functions. This process achieves self-treatment by inhibiting the ferroptosis of neurocytes. In a collagenase and autologous blood injection model-induced mimic postoperative rehemorrhage model, the hydrogel exhibited a 5.58-fold increase in iron absorption efficiency, reducing hematoma size significantly (from 8.674 to 4.768 cubic millimeters). This innovative Hb-responsive DNA hydrogel not only offers a therapeutic intervention for postoperative rehemorrhage but also provides self-diagnosis feedback, holding notable promise for enhancing clinical outcomes.
Subject(s)
Cerebral Hemorrhage , Hemoglobins , Hydrogels , Cerebral Hemorrhage/diagnosis , Cerebral Hemorrhage/drug therapy , Hydrogels/chemistry , Hemoglobins/metabolism , Animals , Deferoxamine/pharmacology , Deferoxamine/therapeutic use , Deferoxamine/chemistry , DNA/metabolism , Humans , Male , Rats , Disease Models, Animal , Ferroptosis/drug effects , Iron/metabolism , Postoperative Hemorrhage/etiology , Postoperative Hemorrhage/diagnosis , Aptamers, Nucleotide/pharmacology , Aptamers, Nucleotide/chemistryABSTRACT
To protect occupants in vehicle cabin environments from the health risks of high concentrations of particulate matter (PM), it is important to install vehicle cabin air filter (VCAF) to eliminate PM. In this study, we investigated the filtration performance of 22 VCAFs. Results showed that the minimum average filtration efficiency was 56.1 % for particles with a diameter of 0.1-0.3 µm, a pressure drop of 33.2-250 Pa at air velocity of 2.5 m/s, and the dust-holding capacity ranged from 5.8 to 19.4 g. In addition, as the filter area increased from 0.23 m2 to 0.50 m2, the filtration efficiency for particles with a diameter of 0.1-0.3 µm increased from 56.7 % to 77.5 %, the pressure drop decreased from 96.1 to 62.5 Pa, and the dust holding capacity increased 2.7 times. Furthermore, we compared the service life of VCAF from 31 major Chinese cities and found that the service life varied greatly from maximum of 1730 h for Haikou to minimum of 352 h for Shijiazhuang. Considering occupant health risks, Beijing requires that VCAFs have PM2.5 filtration efficiency at least 88.1 %, and Liaoning requires minimum of 97.5 %. Hence, choosing the appropriate VCAF based on the atmospheric environment of different cities deserves our attention.
ABSTRACT
Inflammatory bowel diseases (IBD) are often associated with dysregulated gut microbiota and excessive inflammatory microenvironment. Probiotic therapy combined with inflammation management is a promising approach to alleviate IBD, but the efficacy is hindered by the inferior colonization of probiotics in mucus-depleted inflammatory bowel segments. Here, we present modified montmorillonite armed probiotic Escherichia coli Nissle 1917 (MMT-Fe@EcN) with enhanced intestinal colonization and hydrogen sulfide (H2S) scavenging for synergistic alleviation of IBD. The montmorillonite layer that can protect EcN against environmental assaults in oral delivery and improve on-site colonization of EcN in the mucus-depleted intestinal segment due to its strong adhesive capability and electronegativity, with a 22.6-fold increase in colonization efficiency compared to EcN. Meanwhile, MMT-Fe@EcN can manage inflammation by scavenging H2S, which allows for enhancing probiotic viability and colonization for restoring the gut microbiota. As a result, MMT-Fe@EcN exhibits extraordinary therapeutic effects in the dextran sulfate sodium-induced mouse colitis models, including alleviating intestinal inflammation and restoring disrupted intestinal barrier function, and gut microbiota. These findings provide a promising strategy for clinical IBD treatment and potentially other mucus-depletion-related diseases.
ABSTRACT
BACKGROUND: Neoadjuvant therapy (NT) has increased survival rates for patients with locally advanced esophageal cancer (EC), but estimating the impact of NT treatment prior to surgery is still very difficult. METHODS: A retrospective study of the clinical information of 150 patients with locally advanced EC who got NT at Qilu Hospital of Shandong University between June 2018 and June 2023. Patients were randomized into training and internal validation groups at a 3:1 ratio. Furthermore, an external validation cohort comprised 38 patients who underwent neoadjuvant therapy at Qianfoshan Hospital in the Shandong Province between June 2021 and June 2023. Independent risk factors were identified using univariate and multivariate logistic regression (forward stepwise regression). Predictive models and dynamic web nomograms were developed by integrating these risk factors. RESULTS: A total of 188 patients with locally advanced EC were enrolled, of whom 118 achieved stage I of neoadjuvant pathologic TNM (ypTNM) after receiving NT and 129 achieved grades 0-1 in the tumor regression grade (TRG). Logistic regression analysis identified five independent predictors of TRG grades 0-1: pulmonary function tests (PFT), prognostic nutritional index (PNI), triglyceride (TG) levels, squamous cell carcinoma antigen (SCC-Ag) levels, and combination immunotherapy. The areas under the receiver operating characteristic (ROC) curves for the training, internal validation, and external validation groups were 0.87, 0.75, and 0.80, respectively. Meanwhile, two independent predictors of stage I of ypTNM were identified: prealbumin (PA) and SCC antigen. The areas under the ROC curves for the training, internal validation, and external validation groups were 0.78, 0.67, and 0.70, respectively. The Hosmer-Lemeshow test for both predictive models showed excellent calibration, with well-fitted calibration curves. Decision curve analysis (DCA) and clinical impact curves (CIC) have demonstrated that nomograms are of clinical utility. CONCLUSION: The nomograms performed well in predicting the likelihood of stage I of ypTNM and TRG grade 0-1 after NT in patients with locally advanced EC. It helps thoracic surgeons to predict the sensitivity of patients to NT before surgery, which enables precise treatment of patients with locally advanced EC.
Subject(s)
Esophageal Neoplasms , Neoadjuvant Therapy , Neoplasm Staging , Nomograms , Humans , Esophageal Neoplasms/pathology , Esophageal Neoplasms/therapy , Male , Female , Neoadjuvant Therapy/methods , Middle Aged , Retrospective Studies , Prognosis , Follow-Up Studies , Aged , Neoplasm Grading , EsophagectomyABSTRACT
Accurate measurements are critical for timely early warning and effective prevention of epidemics due to the continuing impact of bioaerosols on human health. In recent years, researchers have been focused on developing and calibrating online monitoring instruments. However, there is still a lack of laboratory-generated standard aerosol samples suitable for calibration. Therefore, in this study, we utilized a self-developed Ink Jet Aerosol Generator (H-IJAG) to achieve controllable generation of monodisperse aerosol standard particles. The Aerosol Particle Size Spectrometer (APSS, TOPAS 323) was employed as the particle detector. The diameter of the droplet was calculated by measuring the projected area of the droplet in the same image using Image-J software. Experimental results demonstrated that under standardized inkjet parameters, H-IJAG exhibited good reliability and reproducibility, and generated solid particles within (0.4-15) µm. To better simulate the laser-induced fluorescence emission properties of ambient bioaerosol, tryptophan (Trp) and 7-hydroxycoumarin-4-acetic acid (7-HCA) were selected as solutes of the laboratory-generated aerosol samples, which are known bio-fluorescent materials. According to the law of propagation of uncertainty, the relative uncertainty of the volume equivalent diameter of Trp and 7-HCA solid particles by H-IJAG were 0.42 %, while the relative uncertainty of the particle number concentrations of Trp and 7-HCA solid particles generated by H-IJAG were 1.4 %. This optimized IJAG technique provides a promising solution for the accurate calibration of bioaerosol monitors.
ABSTRACT
BACKGROUND: We found that the occurrence of hepatocellular carcinoma (HCC) has increased significantly in non-cirrhotic individuals, with HCC being frequently overlooked or misdiagnosed. Contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) is known to have a high diagnostic quality in high-risk HCC patients. Therefore, we aimed to compare the detection accuracy of CEUS LI-RADS for HCC between low- and high-risk individuals, to confirm its value in low-risk patients at increased risk of HCC, but not yet included in the high-risk groups of LI-RADS. In addition, since CEUS LR-4 and LR-M categories contain a relatively high proportion of HCC, and serum alpha-fetoprotein (AFP) is the most commonly used biomarker for HCC, and the clinically valid, we attempted to further improve the early diagnostic capability of CEUS LI-RADS for HCC in the low-risk and high-risk patients by combining CEUS LR-4 and LR-M categories with AFP. METHODS: We defined high-risk groups (HR)-included in the high-risk patients of LI-RADS, low-risk groups (LR)-not included in the high-risk patients of LI-RADS and enrolled 189 HCC patients with LR and HR settings in a retrospective study. All lesions were confirmed histopathologically. The CEUS LI-RADS accuracy for detecting HCC in these two patients was compared. In addition, the diagnostic algorithm in our study was proposed (for CEUS LR-4 and LR-M patients with AFP>20 ng/ml). we analyzed the ability of CEUS LI-RADS as a valid method of establishing the early diagnosis of HCC in LR and HR patients by combining LR-4 and LR-M categories with AFP. RESULTS: Through comparative analysis, the specificity of the CEUS LR-5 category for HCC in the HR group was 78.4%, whereas in the LR group, it was 94.2%. Meanwhile, the sensitivity (63.2% vs. 63.0%) and positive predictive value (PPV) (75.0% vs. 88.7%) did not differ between the LR and HR groups ( P = 0.990, P = 0.299). It is noteworthy that there were the high proportion of HCC in CEUS LR-4 and LR-M categories in our cases and when we combined CEUS LR-4 and LR-M categories with AFP significantly improved the sensitivity by 21.0% (84.2%) in the LR group, and by 16.0% (79.0%) in the HR group, with statistically difference in sensitivity after combination in the HR group ( P = 0.014). CONCLUSIONS: The CEUS LR-5 category has real meaningful utility in the diagnosis of HCC in both LR and HR patients. The early detection power of the CEUS LI-RADS category for HCC patients was further increased when the CEUS LR-4 and LR-M categories were combined with elevated AFP.
ABSTRACT
Background: This study aimed to construct a clinical prediction model and nomogram to differentiate invasive from non-invasive pulmonary adenocarcinoma in solitary pulmonary nodules (SPNs). Method: We analyzed computed tomography and clinical features as well as preoperative biomarkers in 1,106 patients with SPN who underwent pulmonary resection with definite pathology at Qilu Hospital of Shandong University between January 2020 and December 2021. Clinical parameters and imaging characteristics were analyzed using univariate and multivariate logistic regression analyses. Predictive models and nomograms were developed and their recognition abilities were evaluated using receiver operating characteristic (ROC) curves. The clinical utility of the nomogram was evaluated using decision curve analysis (DCA). Result: The final regression analysis selected age, carcinoembryonic antigen, bronchus sign, lobulation, pleural adhesion, maximum diameter, and the consolidation-to-tumor ratio as associated factors. The areas under the ROC curves were 0.844 (95% confidence interval [CI], 0.817-0.871) and 0.812 (95% CI, 0.766-0.857) for patients in the training and validation cohorts, respectively. The predictive model calibration curve revealed good calibration for both cohorts. The DCA results confirmed that the clinical prediction model was useful in clinical practice. Bias-corrected C-indices for the training and validation cohorts were 0.844 and 0.814, respectively. Conclusion: Our predictive model and nomogram might be useful for guiding clinical decisions regarding personalized surgical intervention and treatment options.
ABSTRACT
Benzophenone skeletons containing a carbonyl unit (O=C) have been widely used as electron acceptors in the thermally activated delayed fluorescence (TADF) materials. Herein, we present a novel molecular design concept for TADF materials by transitioning from a carbonyl to an amide (O=C-N) skeleton as the acceptor. The amide unit, compared to its carbonyl counterpart, offers a more stable electronic configuration. Leveraging this insight, we have developed a series of high-performance TADF molecules based on benzoyl carbazole and carbazoline acceptors. These molecules exhibit exceptionally small singlet-triplet energy gaps and pronounced aggregation-enhanced emission properties, achieving photoluminescence quantum yields in neat films as high as 99%. Consequently, these materials serve as efficient emitters in non-doped organic light-eimtting diodes (OLEDs), reaching a maximum quantum efficiency (EQEmax) of up to 26.0%, significantly higher than the 17.0% obtained with benzophenone acceptor-based TADF molecules. Additionally, they have been used as TADF hosts in narrowband red fluorescent OLEDs, setting a record-high EQEmax of 22.4%.
ABSTRACT
CasX (also known as Cas12e), a Class 2 CRISPR-Cas system, shows promise in genome editing due to its smaller size compared to the widely used Cas9 and Cas12a. Although the structures of CasX-sgRNA-DNA ternary complexes have been resolved and uncover a distinctive NTSB domain, the dynamic behaviors of CasX are not well characterized. In this study, we employed single-molecule and biochemical assays to investigate the conformational dynamics of two CasX homologs, DpbCasX and PlmCasX, from DNA binding to target cleavage and fragment release. Our results indicate that CasX cleaves the non-target strand and the target strand sequentially with relative irreversible dynamics. The two CasX homologs exhibited different cleavage patterns and specificities. The dynamic characterization of CasX also reveals a PAM-proximal seed region, providing guidance for CasX-based effector design. Further studies elucidate the mechanistic basis for why modification of sgRNA and the NTSB domain can affect its activity. Interestingly, CasX has less effective target search efficiency than Cas9 and Cas12a, potentially accounting for its lower genome editing efficiency. This observation opens a new avenue for future protein engineering.
ABSTRACT
Cancer poses a major threat to human health worldwide. The development of anti-tumor materials provides new modalities for cancer diagnosis and treatment. In this review, we comprehensively summarize the research progress and clinical applications of anti-tumor materials. First, we introduce the etiology and pathogenesis of cancer, and the significance and challenges of anti-tumor materials research. Then, we classify anti-tumor materials and discuss their mechanisms of action. After that, we elaborate the research advances and clinical applications of anti-tumor materials, including those targeting tumor cells and therapeutic instruments. Finally, we discuss the future perspectives and challenges in the field of anti-tumor materials. This review aims to provide an overview of the current status of anti-tumor materials research and application, and to offer insights into future directions in this rapidly evolving field, which holds promise for more precise, efficient and customized treatment of cancer.
Subject(s)
Antineoplastic Agents , Neoplasms , Humans , Neoplasms/drug therapy , Neoplasms/therapy , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/pharmacology , Molecular Targeted Therapy/methods , Animals , Drug Delivery Systems/methodsABSTRACT
Therapeutic cancer vaccines are among the first FDA-approved cancer immunotherapies. Among them, it remains a major challenge to achieve robust lymph-node (LN) accumulation. However, delivering cargo into LN is difficult owing to the unique structure of the lymphatics, and clinical responses have been largely disappointing. Herein, inspired by the Migrated-DCs homing from the periphery to the LNs, an injectable hydrogel-based polypeptide vaccine system is described for enhancing immunostimulatory efficacy, which could form a local niche of vaccine "hitchhiking" on DCs. The OVA peptide modified by lipophilic DSPE domains in the hydrogel is spontaneously inserted into the cell membrane to achieve "antigen anchoring" on DCs in vivo. Overall, OVA peptide achieves active access LNs through recruiting and "hitchhiking" subcutaneous Migrated-DCs. Remarkably, it is demonstrated that the composite hydrogel enhances LNs targeting efficacy by approximately six-fold compared to free OVA peptide. Then, OVA peptide can be removed from the cell surface under a typical acidic microenvironment within the LNs, further share them with LN-resident APCs via the "One-to-Many" strategy (One Migrated-DC corresponding to Many LN-resident APCs), thereby activating powerful immune stimulation. Moreover, the hydrogel vaccine exhibits significant tumor growth inhibition in melanoma and inhibits pulmonary metastatic nodule formation.
ABSTRACT
Hyperthermia therapy is considered an effective anticancer strategy. However, high temperature can trigger an excessive inflammatory response, leading to tumor self-protection, immunosuppression, metastasis, and recurrence. To address this issue, we reported a multifunctional photothermal nanoplatform to achieve mild hyperthermia photothermal therapy (mild PTT) based on cisplatin (DDP) and a ferrocene metal-organic framework (MOF-Fc) nanocomposite, which can specifically enhance ferroptosis-triggered oxidative stress levels and synchronously amplify mild hyperthermia PTT-mediated anticancer responses. Both in vitro and in vivo antineoplastic results verify the superiority of mild PTT with DDP/MOF-Fc@HA. The combination of DDP and MOF-Fc exhibits Fenton catalytic activity and glutathione depletion capacity, magnifying mild hyperthermia effects via the radical oxygen species (ROS)-adenosine triphosphate (ATP)-HSP silencing pathway, with important implications for clinical hyperthermia therapy.
ABSTRACT
Long-term atmospheric nitrogen (N) deposition has been known to enhance plant productivity by increasing available N in terrestrial ecosystems. However, the response of carbon process to N deposition in terrestrial ecosystems remains unclear, particularly about different climate regions and biomes. In this study, we synthesized 1281 pairwise observations from 218 published articles on experimental N addition globally, aiming to quantify the responses of the carbon process and its mechanisms to N addition. Our results revealed a significant overall increase in net ecosystem productivity (NEP) by 31.42 % following N addition treatment, owing to increased aboveground net primary productivity (ANPP, 16.46 %), belowground net primary productivity (BNPP, 27.74 %), and reduced soil respiration (Rs, -2.56 %), soil heterotrophic respiration (Rh, -6.24 %). Furthermore, the effects of N addition on NEP varied with biomes and climate regions. The positive effect of N addition on NEP was more pronounced in arid regions (28.67 %) compared to humid regions (21.92 %), primarily driven by a higher increase in vegetation productivity. Additionally, N addition exhibited a higher increase in NEP (33.95 %) in forest compared to grassland (31.80 %), resulting from a more reduction in respiratory processes. However, the positive effects of N addition on NEP diminished with increasing experimental duration. Furthermore, ANPP and BNPP displayed a convex relationship with N addition rates, with the optimum BNPP addition rate exceeding that of ANPP. In contrast, Rs exhibited a concave response to addition rates. These findings suggest that carbon sink in terrestrial ecosystems could be enhanced under future atmospheric N deposition, especially in arid regions and forest ecosystems. Our study provided insight for predicting how N deposition influences terrestrial ecosystem carbon process.
Subject(s)
Carbon Sequestration , Ecosystem , Nitrogen , Carbon/metabolism , Soil/chemistry , ForestsABSTRACT
Outstanding overall mechanical properties are essential for the successful utilization of hydrogels in advanced applications such as human-machine interfaces and soft robotics. However, conventional hydrogels suffer from fracture toughness-stiffness conflict and fatigue threshold-stiffness conflict, limiting their applicability. Simultaneously enhancing the fracture toughness, fatigue threshold, and stiffness of hydrogels, especially within a homogeneous single network structure, has proven to be a formidable challenge. In this work, we overcome this challenge through the design of a loosely cross-linked hydrogel with slight dehydration. Experimental results reveal that the slightly-dehydrated, loosely cross-linked polyacrylamide hydrogel, with an original/current water content of 87%/70%, exhibits improved mechanical properties, which is primarily attributed to the synergy between the long-chain structure and the dense dehydration-induced entanglements. Importantly, the creation of these microstructures does not require intricate design or processing. This simple approach holds significant potential for hydrogel applications where excellent anti-fracture and fatigue-resistant properties are necessary.
ABSTRACT
In semi-supervised learning (SSL), many approaches follow the effective self-training paradigm with consistency regularization, utilizing threshold heuristics to alleviate label noise. However, such threshold heuristics lead to the underutilization of crucial discriminative information from the excluded data. In this paper, we present OTAMatch, a novel SSL framework that reformulates pseudo-labeling as an optimal transport (OT) assignment problem and simultaneously exploits data with high confidence to mitigate the confirmation bias. Firstly, OTAMatch models the pseudo-label allocation task as a convex minimization problem, facilitating end-to-end optimization with all pseudo-labels and employing the Sinkhorn-Knopp algorithm for efficient approximation. Meanwhile, we incorporate epsilon-greedy posterior regularization and curriculum bias correction strategies to constrain the distribution of OT assignments, improving the robustness with noisy pseudo-labels. Secondly, we propose PseudoNCE, which explicitly exploits pseudo-label consistency with threshold heuristics to maximize mutual information within self-training, significantly boosting the balance of convergence speed and performance. Consequently, our proposed approach achieves competitive performance on various SSL benchmarks. Specifically, OTAMatch substantially outperforms the previous state-of-the-art SSL algorithms in realistic and challenging scenarios, exemplified by a notable 9.45% error rate reduction over SoftMatch on ImageNet with 100K-label split, underlining its robustness and effectiveness.
ABSTRACT
Antitumor agents often lack effective penetration and accumulation to achieve high therapeutic efficacy in treating solid tumors. Nanomotor-based nanomaterials offer a potential solution to address this obstacle. Among them, nitric oxide (NO) based nanomotors have garnered attention for their potential applications in nanomedicine. However, there widespread clinical adoption has been hindered by their complex preparation processes. To address this limitation, we have developed a NO-driven nanomotor utilizing a convenient and scalable nanogel preparation procedure. These nanomotors, loaded with the fluorescent probe / sonosensitizer chlorin e6 (Ce6), were specifically engineered for sonodynamic therapy. Through comprehensive in vitro investigations using both 2D and 3D cell models, as well as in vivo analysis of Ce6 fluorescent signal distribution in solid tumor models, we observed that the self-propulsion of these nanomotors significantly enhances cellular uptake and tumor penetration, particularly in solid tumors. This phenomenon enables efficient access to challenging tumor regions and, in some cases, results in complete tumor coverage. Notably, our nanomotors have demonstrated long-term in vivo biosafety. This study presents an effective approach to enhancing drug penetration and improving therapeutic efficacy in tumor treatment, with potential clinical relevance for future applications.
Subject(s)
Chlorophyllides , Nanogels , Neoplasms , Nitric Oxide , Porphyrins , Animals , Nitric Oxide/administration & dosage , Nitric Oxide/metabolism , Humans , Neoplasms/drug therapy , Neoplasms/therapy , Neoplasms/metabolism , Porphyrins/administration & dosage , Porphyrins/pharmacokinetics , Cell Line, Tumor , Nanogels/chemistry , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/pharmacokinetics , Polyethylene Glycols/chemistry , Mice, Nude , Polyethyleneimine/chemistry , Mice, Inbred BALB C , Fluorescent Dyes/chemistry , Fluorescent Dyes/administration & dosage , Female , Mice , Ultrasonic Therapy/methods , Nanostructures/administration & dosageABSTRACT
The misuse of antibiotics may contaminate the environment and cause harm to human health. Therefore, rapid and accurate detection of antibiotics is essential. In this study, a novel electrochemiluminescence resonance energy transfer (ECL-RET) pair was designed using a new ECL emitter (CPM, Ce-TBAPy) as the donor and Co-MOF@AuPt as the acceptor. Moreover, a highly sensitive and specific "on-off-on" ECL aptasensor was constructed for detecting sulfadiazine (SDZ). The aptasensor exhibited a broad linear range (from 10.0 fg mL-1 to 100 ng mL-1) for the SDZ concentration, with limit of detection and limit of quantification values of 1.14 fg mL-1and 3.75 fg mL-1, respectively. The aptasensor achieved good results in spiking experiments with milk and egg samples, and successfully quantified SDZ in fish meal quality control sample. The prepared aptasensor presents great potential for food and environmental safety by detecting antibiotics.