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"Yu, Jingjing"
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Reversing insufficient photothermal therapy-induced tumor relapse and metastasis by regulating cancer-associated fibroblasts
Insufficient tumor accumulation and distribution of photosensitizers as well as low antitumor immunity severely restrict the therapeutic efficacy of photothermal therapy (PTT). Cancer-associated fibroblasts (CAFs) play a key role in tumor extracellular matrix (ECM) remodeling and immune evasion. Reshaping tumor microenvironment via CAF regulation might provide a potential approach for complete tumor elimination in combination with PTT. Here, tumor cell-derived microparticles co-delivering calcipotriol and Indocyanine green (Cal/ICG@MPs) are developed to modulate CAFs for improved PTT efficacy. Cal/ICG@MPs efficiently target tumor tissues and regulate CAFs to reduce tumor ECM, resulting in enhanced tumor accumulation and penetration of ICG to generate strong PTT efficacy and activate CD8
+
T cell-mediated antitumor immunity. In addition, Cal/ICG@MPs-triggered CAF regulation enhances tumor infiltration of CD8
+
T cells and ameliorates CAF-induced antigen-mediated activation-induced cell death of tumor-specific CD8
+
T cells in response to PTT, eliciting long-term antitumor immune memory to inhibit tumor recurrence and metastasis. Our results support Cal/ICG@MPs as a promising drug to improve PTT efficacy in cancer treatment.
Photothermal therapy (PTT) has emerged as a promising approach for cancer treatment. Here, in preclinical cancer models, the authors show that PTT efficacy could be improved using tumor cell-derived microparticles that co-deliver the photosensitizer indocyanine green and a vitamin-D receptor ligand, calcipotriol, resulting in tumor extracellular matrix remodelling and ameliorated anti-tumor immune responses.
Journal Article
CXCR4-Targeted Radiopharmaceuticals for the Imaging and Therapy of Malignant Tumors
C-X-C chemokine receptor type 4 (CXCR4), also known as fusin or CD184, is a 7-transmembrane helix G-protein-coupled receptor that is encoded by the CXCR4 gene. Involved in various physiological processes, CXCR4 could form an interaction with its endogenous partner, chemokine ligand 12 (CXCL12), which is also named SDF-1. In the past several decades, the CXCR4/CXCL12 couple has attracted a large amount of research interest due to its critical functions in the occurrence and development of refractory diseases, such as HIV infection, inflammatory diseases, and metastatic cancer, including breast cancer, gastric cancer, and non-small cell lung cancer. Furthermore, overexpression of CXCR4 in tumor tissues was shown to have a high correlation with tumor aggressiveness and elevated risks of metastasis and recurrence. The pivotal roles of CXCR4 have encouraged an effort around the world to investigate CXCR4-targeted imaging and therapeutics. In this review, we would like to summarize the implementation of CXCR4-targeted radiopharmaceuticals in the field of various kinds of carcinomas. The nomenclature, structure, properties, and functions of chemokines and chemokine receptors are briefly introduced. Radiopharmaceuticals that could target CXCR4 will be described in detail according to their structure, such as pentapeptide-based structures, heptapeptide-based structures, nonapeptide-based structures, etc. To make this review a comprehensive and informative article, we would also like to provide the predictive prospects for the CXCR4-targeted species in future clinical development.
Journal Article
Boosting anti-PD-1 therapy with metformin-loaded macrophage-derived microparticles
The main challenges for programmed cell death 1(PD-1)/PD-1 ligand (PD-L1) checkpoint blockade lie in a lack of sufficient T cell infiltration, tumor immunosuppressive microenvironment, and the inadequate tumor accumulation and penetration of anti-PD-1/PD-L1 antibody. Resetting tumor-associated macrophages (TAMs) is a promising strategy to enhance T-cell antitumor immunity and ameliorate tumor immunosuppression. Here, mannose-modified macrophage-derived microparticles (Man-MPs) loading metformin (Met@Man-MPs) are developed to efficiently target to M2-like TAMs to repolarize into M1-like phenotype. Met@Man-MPs-reset TAMs remodel the tumor immune microenvironment by increasing the recruitment of CD8
+
T cells into tumor tissues and decreasing immunosuppressive infiltration of myeloid-derived suppressor cells and regulatory T cells. More importantly, the collagen-degrading capacity of Man-MPs contributes to the infiltration of CD8
+
T cells into tumor interiors and enhances tumor accumulation and penetration of anti-PD-1 antibody. These unique features of Met@Man-MPs contribute to boost anti-PD-1 antibody therapy, improving anticancer efficacy and long-term memory immunity after combination treatment. Our results support Met@Man-MPs as a potential drug to improve tumor resistance to anti-PD-1 therapy.
Durable response rate to anti-PD-1/PD-L1 therapy remains relatively low in patients with cancer. Here the authors show that metformin-loaded mannose-modified macrophage-derived microparticles reprogram the tumor immune microenvironment and improve responses to anti-PD-1 therapy.
Journal Article
Comprehensive Analyses of Advanced Glycation end Products and Heterocyclic Amines in Peanuts during the Roasting Process
Advanced glycation end products (AGEs) and heterocyclic amines (HAs) are two kinds of important harmful products formed simultaneously during the thermal processing of proteinaceous food. In this paper, the effect of roasting conditions on the formation of AGEs and HAs, as well as active carbonyl intermediates in common peanut (C−peanut) and high-oleic acid peanut (HO−peanut) was studied simultaneously for the first time. In general, with the increase in roasting temperature (160–200 °C) and time, the contents of AGEs, HAs and active carbonyl intermediates (i.e., glyoxal (GO) and methylglyoxal (MGO)) significantly increased in peanuts. Four kinds of HAs (i.e., AαC, DMIP, Harman and Norharman) were observed in roasted peanuts, of which Harman and Norharman accounted for about 93.0% of the total HAs content after roasting for 30 min at 200 °C. Furthermore, a correlation analysis among AGEs (i.e., Nε-(1-Carboxymethyl)-L-lysine (CML) and Nε-(1-Carboxyethyl)-L-lysine (CEL)), HAs, GO and MGO was conducted. Most of these compounds showed an excellent positive linear relationship (p ≤ 0.001) with each other. The evident increase in GO and MGO contents implied an increase in not only the content of AGEs but also HAs. However, contents of AGEs and HAs showed no significant difference between roasted HO−peanut and C−peanut. This study would provide a theoretical basis for simultaneously controlling the levels of AGEs and HAs in thermal processed peanut foods.
Journal Article
Immunoinformatics method to design universal multi-epitope nanoparticle vaccine for TGEV S protein
Porcine transmissible enteritis virus (TGEV) is a fatal pathogen affecting newborn piglets, presenting a significant challenge to global intensive pig farming biosecurity due to its ongoing mutation. There is still a lack of effective vaccines to combat this virus, Vaccination has long been considered the most effective way to overcome infectious diseases, however, traditional vaccines cannot be brought to market quickly enough to deal with rapid mutations and emerging viruses. Therefore, this study addresses this gap by using immunoinformatics methods and ferritin nanoparticle delivery system to build a platform for rapid research and development of porcine coronavirus vaccine, designing a candidate nanoparticle vaccine that targets the TGEV S protein. To this end, multiple servers and strict screening criteria were used to analyze the S protein, and 3 CTL dominant epitopes, 3 Th dominant epitopes, and 6 B cell dominant epitopes were obtained. The candidate nanoparticle vaccine was constructed by incorporating ferritin sequences through the C-terminus after they were tandemly linked in a certain order using a flexible linker. Further experimental analyses showed that the designed candidate nanoparticle vaccine possessed relatively high antigenicity, immunogenicity, non-allergenicity, non-transmembrane proteins, suitable physicochemical properties, and high solubility upon overexpression. Tertiary structure modeling and disulfide engineering ensured conformational similarity to natural proteins and high stability. Additionally, the model predicted 6 Linear Epitopes and 6 Discontinuous Epitopes for B-cell conformational epitopes. Docking with TLR-3 and TLR-4 molecules shows a large number of interacting hydrogen-bonded amino acid residues and hydrophobically interacting amino acid residues. Immunomimetic assays show high levels of immunoglobulin, T-lymphocyte and IFN-γ secretion and may elicit specific immune responses. Through computerized cloning, the candidate nanoparticle vaccine can be efficiently expressed in the
E. coli K12
expression system, aligning with future large-scale industrial production strategies. Overall, the results indicate that the constructed candidate nanoparticle vaccine can be effectively expressed and may be able to induce a strong immune response, which is expected to be an ideal candidate vaccine against TGEV.
Journal Article
The mediating role of ego depletion in the relationship between state anxiety and academic procrastination among University students
The issue of academic procrastination is highly prevalent among university students. It not only has a deterimental effect on students' academic performance but also poses a risk to their physical and mental well-being. Anxiety, as a negative emotion, has attracted researchers’ attention in relation to academic procrastination. Research indicates a correlation between state anxiety and academic procrastination, but the underlying mechanisms that drive this association remain unclear. When individuals experience ego-depletion, it can lead to psychological exhaustion, subsequently leading to procrastination. Gender role conceptions, shaped by sociocultural and psychological mechanisms, have profound implications on individuals’ cognition, emotions, and behaviors. This study primarily aims to explore the relationship between state anxiety and academic procrastination among university students, with a particularly focus on the mediating role of ego-depletion and the moderating role of gender. A survey using the State Anxiety Scale, Ego-Depletion Scale, and Irrational Procrastination Scale was administered to 3370 undergraduates. State anxiety shows positive correlations with ego depletion and academic procrastination (
r
= 0.665,
p
< 0.01;
r
= 0.491,
p
< 0.01), while ego depletion is also positively linked to academic procrastination (
r
= 0.500,
p
< 0.01). State anxiety serves as a positive predictor of academic procrastination, with a confidence interval of 95% [0.626, 0.696]; additionally, ego depletion partially mediates the relationship between state anxiety and academic procrastination, with a confidence interval of 95% [0.168, 0.251]. Gender acts as a moderator in directly predicting the impact of state anxiety on academic procrastination and in the latter stage of mediating the effect of ego depletion. State anxiety can significantly and positively predict academic procrastination among university students. Ego-depletion partially mediates the relationship between state anxiety and academic procrastination. The direct predictive effect of state anxiety on academic procrastination, as well as the mediating role of ego-depletion, is moderated by gender. This provides educators and university students themselves with reference for addressing the issue of academic procrastination.
Journal Article
Chinese dental students’ knowledge, attitudes, and practice regarding traumatic dental injuries in immature permanent teeth
Background
The appropriate management of traumatic dental injuries (TDIs) in immature permanent teeth is critical for predicting prognosis and preserving injured teeth. However, providing accurate treatment is always challenging for dental students due to their limited knowledge of TDIs. This study aimed to assess TDIs in immature permanent teeth in terms of knowledge, attitudes, and clinical practice among Chinese dental undergraduates and residents.
Methods
Dental undergraduates (in 3rd -, 4th -, and 5th -years) and residents (in 1st -, 2nd -, and 3rd -years) at the School of Stomatology, Wuhan University (763 in total, from May to June 2024), were distributed with a structured electronic questionnaire containing 22 items. The obtained data was statistically analyzed via the Chi-square (χ
2
) test (
p
< 0.05) using SPSS.
Results
Participants from various academic levels completed 502 questionnaires, with a response rate of 65.79%. Approximately half of the participants (58.6%) were familiar with TDIs, chiefly through traditional classroom learning (90.0%). Participants had limited knowledge on correct emergency treatment for TDIs, including tooth replantation timing (51.6%), fixation method (43.8%), and time (25.5%), with 3rd -year undergraduates reporting the lowest percentage (10.2%) (
p
< 0.05). Most participants agreed that vital pulp preservation (95.0%) and additional examination (91.0%) are essential for TDI management. Besides, only 29.9% of participants had ever treated a clinical TDI case independently. The majority of participants expressed a strong desire to gain comprehensive knowledge of TDIs (90.0%) and additional training (96.4%).
Conclusions
Dental students at the undergraduate and postgraduate levels lacked sufficient knowledge and practice with TDIs but had a positive attitude toward TDI management. Thus, it would be enormously beneficial for dental students to gain a better understanding of TDIs through improved dental education, including multiple teaching methodologies and more clinical practice.
Clinical trial number
Not applicable.
Journal Article
Design, synthesis and applications of responsive macrocycles
Inspired by the lock and key principle, the development of supramolecular macrocyclic chemistry has promoted the prosperous growth of host-guest chemistry. The updated induced-fit and conformation selection model spurred the emerging research on responsive macrocycles (RMs). This review introduces RMs, covering their design, synthesis and applications. It gives readers insight into the dynamic control of macrocyclic molecules and the exploration of materials with desired functions.
Macrocycles have been widely studied for their structure-specific and highly selective recognition properties. Here the authors review the design, synthesis and applications of photo-, pH- and redox-responsive macrocycles.
Journal Article
Knowledge, attitudes, and practices of dental residents in managing traumatic dental injuries
Background
Traumatic dental injuries (TDIs) are common emergencies, particularly in children and adolescents, requiring prompt and effective management to ensure favorable outcomes. However, dental residents' preparedness in managing TDIs remains understudied, especially in the context of educational and clinical practice gaps. This study aimed to evaluate the knowledge, attitudes, and practices (KAP) of dental residents regarding TDI management, with a focus on identifying training deficiencies and informing curricular improvements.
Methods
A survey was conducted among 256 dental residents from the School of Stomatology, Wuhan University, China. A validated electronic questionnaire was distributed to assess demographic characteristics, clinical exposure, knowledge competency, professional attitudes, and practice patterns related to TDIs. Data were analyzed using descriptive statistics and chi-square tests.
Results
While 88.7% of residents encountered TDIs, only 67.2% felt confident in management protocols, with significant disparities across specialties (
P
= 0.038). Traditional classroom teaching was the primary learning method (87.7%), whereas online resources were less frequently used (9.7% in Oral Surgery). Only 28.1% expressed satisfaction with traditional teaching methods. Although 94.5% acknowledged the importance of pulp preservation, 6.9% of General Dentistry residents held uncertain attitudes. Clinical independence varied, with 63.8% of General Dentistry residents occasionally managing cases independently, compared to 77.4% of Oral Surgery residents who never did.
Conclusions
Dental residents recognize the clinical importance of TDI management, but gaps in knowledge translation, uneven specialty training, and reliance on outdated pedagogies hinder clinical readiness. Reforms incorporating blended learning, simulation-based training, and competency-based assessments are urgently needed to optimize residents' education and patient care.
Journal Article