Application of PRI-E-a combined learning method in oral and maxillofacial oncology education.

The traditional lecture-based learning (LBL) method is facing great challenges due to its low efficiency and single proceeding form. We designed a PRI-E learning mode that combined and modified problem-based, case-based, and evidence-based learning with a step-by-step approach. We evaluated the practical learning outcomes of using the PRI-E mode by comparing it with traditional lecture-based learning in oral and maxillofacial oncology education. "PRI-E" consists of the first letters of the English words Passion, Research, Innovation, and Education, and it means "the best Education". This prospective randomized controlled trial included 40 participants. We evenly divided the participants into the PRI-E (n = 20) and LBL group (n = 20) based on the entrance test scores. The same staff group designed and then taught the learning content with different group measures. The evaluation included the final test scores and questionnaire assessments. Without affecting the examination results, the PRI-E teaching method was more satisfactory and popular with participants in terms of ability development and classroom participation. Enacting the PRI-E teaching method required more time, but this did not affect its popularity among the participants. Compared with the LBL learning mode, the PRI-E learning mode was more organized and efficient in oral and maxillofacial oncology education without affecting academic performance. This model has a high degree of satisfaction, which is conducive to training students' comprehensive ability.

Enhanced lipid biosynthesis in oral squamous cell carcinoma cancer-associated fibroblasts contributes to tumor progression: Role of IL8/AKT/p-ACLY axis.

Lipid metabolic reprogramming of tumor cells has been proven to play a critical role in tumor initiation and development. However, lipid metabolism in cancer-associated fibroblasts (CAFs) has rarely been studied, particularly in CAFs of oral squamous cell carcinoma (OSCC). Additionally, the molecular mechanism by which tumor cells regulate lipid metabolism in fibroblasts is unclear. In this study, we found that phosphorylated ATP citrate lyase (p-ACLY), a key lipid metabolic enzyme, was upregulated in OSCC CAFs. Compared to paracancerous normal fibroblasts, CAFs showed enhanced lipid synthesis, such as elevated cytosolic acetyl-CoA level and accumulation of lipid droplets. Conversely, reduction of p-ACLY level blocked this biological process. In addition, blocking lipid synthesis in CAFs or inhibiting fatty acid uptake by OSCC cells reduced the promotive effects of CAFs on OSCC cell proliferation, invasion, and migration. These findings suggested that CAFs are one of lipid sources required for OSCC progression. Mechanistically, AKT signaling activation was involved in the upregulation of p-ACLY level and lipid synthesis in CAFs. Interleukin-8 (IL8), an exocrine cytokine of OSCC cells, could activate AKT and then phosphorylate ACLY in fibroblasts. This study suggested that the IL8/AKT/p-ACLY axis could be considered as a potential target for OSCC treatment.

Melatonin inhibits the stemness of head and neck squamous cell carcinoma by modulating HA synthesis via the FOSL1/HAS3 axis.

Hyaluronic acid (HA) is a glycosaminoglycan and the main component of the extracellular matrix (ECM), which has been reported to interact with its receptor CD44 to play critical roles in the self-renewal and maintenance of cancer stem cells (CSCs) of multiple malignancies. Melatonin is a neuroendocrine hormone with pleiotropic antitumor properties. However, whether melatonin could regulate HA accumulation in the ECM to modulate the stemness of head and neck squamous cell carcinoma (HNSCC) remains unknown. In this study, we found that melatonin suppressed CSC-related markers, such as CD44, of HNSCC cells and decreased the tumor-initiating frequency of CSCs in vivo. In addition, melatonin modulated HA synthesis of HNSCC cells by downregulating the expression of hyaluronan synthase 3 (HAS3). Further study showed that the Fos-like 1 (FOSL1)/HAS3 axis mediated the inhibitory effects of melatonin on HA accumulation and stemness of HNSCC in a receptor-independent manner. Taken together, melatonin modulated HA synthesis through the FOSL1/HAS3 axis to inhibit the stemness of HNSCC cells, which elucidates the effect of melatonin on the ECM and provides a novel perspective on melatonin in HNSCC treatment.

Modified chitosan with different phenolic acids: Characterization, physicochemical properties, and biological activity.

This study synthesized five phenolic acid-chitosan copolymers utilizing the carbodiimide-mediated chemical crosslinking reaction. Comprehensive evaluations were conducted on their structural attributes, physicochemical properties, and biological activities. Fourier transform infrared confirmed successful grafting of phenolic acids onto chitosan via amide linkages. Additionally, ultraviolet-visible absorption spectroscopy and proton nuclear magnetic resonance analyses revealed novel absorption peaks between 200 and 400 nm and 6.0-8.0 ppm, respectively, attributable to the incorporated phenolic acids. Notably, the chitosan-gentisate acid copolymer exhibited significantly enhanced biological activity (p < 0.05) compared to pure chitosan and the other four conjugates, attributed to its highest grafting degree of approximately 295.93 mg/g. These modified chitosan derivatives effectively preserved the quality of sea bass (Lateolabrax japonicus) during refrigerated storage, extending its shelf-life by up to 9 days, 7 days, and 4 days relative to control, chitosan, and gentisate acid groups.

Effects of slightly acidic electrolyzed water combined with ԑ-polylysine-chitooligosaccharide Maillard reaction products treatment on the quality of vacuum packaged sea bass (Lateolabrax japonicas).

In this study, a new natural preservative, ε-polylysine (ε-PL) and chitooligosaccharides (COS) Maillard reaction products (LC-MRPs), was prepared by Maillard reaction. The preservation effect of LC-MRPs combined with slightly acidic electrolyzed water (SAEW) pretreatment (SM) on vacuum-packed sea bass during refrigerated storage was evaluated. The results showed that after 16 days, SM treatment could effectively inhibit the microbial growth and prevent water migration in sea bass. In addition, the highest water holding capacity (69.79 %) and the best sensory characteristics, the lowest malonaldehyde (MDA) (58.96 nmol/g), trimethylamine (TMA) (3.35 mg/100 g), total volatile basic nitrogen (TVB-N) (16.93 mg N/100 g), myofibril fragmentation index (MFI) (92.2 %) and TCA-soluble peptides (2.16 µmol tyrosine/g meat) were related to SM group. Combined with sensory analysis, we can conclude that the combined treatment of SAEW and LC-MRPs could prolong the shelf-life of sea bass for another 11 days compared with the DW group. Results disclosed that the composite treatment of SAEW and LC-MRPs is a promising technology to improve the shelf-life of vacuum-packed sea bass during refrigerated storage.

Efficacy of personalized 3D-printed osteotomy guide in maximizing fibular utilization and minimizing graft length for reconstruction of large mandibular defect.

OBJECTIVE: The study addresses the long-standing challenge of insufficient length in vascularized fibular flaps when reconstructing large mandibular defects that require dual-barrel grafts. Employing personalized 3D-printed osteotomy guides, the study aims to optimize fibular utilization and minimize the required graft length. MATERIAL AND METHODS: Two reconstruction methods for distal bone defects were compared: a fold-down (FD) group that employed a specialized osteotomy guide for folding down a triangular bone segment, and a traditional double-barrel (DB) group. Metrics for comparison included defect and graft lengths, as well as the graft-to-defect length ratio. Postoperative quality of life was assessed using the University of Washington Quality of Life questionnaire (UW-QoL). RESULT: Both FD and DB groups achieved successful mandibular reconstruction. Despite larger defects in the FD group (117 ± 31.35 mm vs 84 ± 35.34 mm, p = 0.028), the used fibula length was not statistically longer in the FD group. The median ratio of graft-to-defect length was also lower in the FD group (1.327 vs 1.629, p = 0.024), suggesting that FD required only 82.47% of the graft length needed in the DB approach. Quality of life scores post-surgery were comparable between the groups. CONCLUSION: Personalized 3D-printed osteotomy guides enhance fibula graft efficacy for reconstructing larger mandibular defects, necessitating shorter graft lengths while preserving postoperative quality of life. CLINICAL RELEVANCE: This study confirms the utility of 3D printing technology as an effective and precise tool in orthopedic surgery, particularly for complex reconstructions like large mandibular defects. It suggests a viable alternative that could potentially revolutionize current practices in bone grafting.

Trinuclear Re(I)-Coordinated Organic Cage as the Supramolecular Photocatalyst for Visible-Light-Driven CO2 Reduction.

Photocatalytic reduction of excess CO2 in the atmosphere to value-added chemicals by visible light can be an effective solution to fuel shortage and global warming. Considering these issues, we designed and successfully synthesized a trinuclear Re(I)-coordinated organic cage (Re-C4R) as the supramolecular photocatalyst. Photophysical, electrochemical properties, and photocatalytic performance comparison of Re-C4R and its mononuclear analogue Re-bpy are discussed in detail. Notably, the covalent linkage of three Re(I) subunits in Re-C4R leads to TONCO = 691 (per Re(I) site in 4 h) more than three times as much as TONCO = 208 of Re-bpy. Compared to Re-bpy, higher current enhancement in the control CV experiments under CO2 was observed for Re-C4R. CO2 adsorption process can be promoted because of the cryptand structure and multiple amine groups of Re-C4R. Moreover, decay lifetimes of Re-C4R are shorter than those of Re-bpy in the ultrafast transient absorption (TA) and photoluminescence (PL) decay spectra, indicating that the trinuclear cryptate structure of Re-C4R could facilitate electron transfer efficiency during CO2 reduction.

Dentinogenic ghost cell tumor revisited from a single institution in China with focus on adenoid ameloblastoma-like features.

OBJECTIVE: The present study aims to identify adenoid ameloblastoma (AdAM) from previously diagnosed cases of dentinogenic ghost cell tumor (DGCT), and gain insight to the possible relationship between AdAM and DGCT. METHODS: DGCT cases diagnosed between 2006 and 2022 were re-examined with focus on the AdAM-like features. RESULTS: A total of nine patients were included. Seven patients were males and two were females. The mean age was 38.0 ± 16.0 years. Five tumors occurred in the maxilla and four in the mandible, with a remarkable predilection for the posterior regions of both jaws. Microscopically, dentinoid material deposition was present in all cases. The ghost cells were absent in two cases. Rare ghost cells (<1%) were observed in three cases, and a higher proportion of ghost cells (5%-20%) were present in the remaining four cases. All cases showed prominent AdAM-like features, including duct-like structures, whorls/morules, and cribriform architecture. According to the diagnostic criteria proposed by the 2022 WHO classification, five cases without or with rare ghost cells were reclassified as AdAM. The other four cases including a higher proportion of ghost cells consisted of a mixture of DGCT and AdAM histopathologic patterns. CONCLUSION: Our results confirmed that the AdAM-like features had been largely overlooked in the diagnosis of DGCT at our institution in the past. Whilst a subset can now be more accurately classified as AdAM, some tumors showed overlapping morphological features between AdAM and DGCT, suggesting that the two may represent a spectrum of the same entity.

One/Two-Photon-Excited ESIPT-Attributed Coordination Polymers with Wide Temperature Range and Color-Tunable Long Persistent Luminescence.

The multiple metastable excited states provided by excited-state intramolecular proton transfer (ESIPT) molecules are beneficial to bring temperature-dependent and color-tunable long persistent luminescence (LPL). Meanwhile, ESIPT molecules are intrinsically suitable to be modulated as D-π-A structure to obtain both one/two-photon excitation and LPL emission simultaneously. Herein, we report the rational design of a dynamic CdII coordination polymer (LIFM-106) from ESIPT ligand to achieve the above goals. By comparing LIFM-106 with the counterparts, we established a temperature-regulated competitive relationship between singlet excimer and triplet LPL emission. The optimization of ligand aggregation mode effectively boost the competitiveness of the latter. In result, LIFM-106 shows outstanding one/two-photon excited LPL performance with wide temperature range (100-380 K) and tunable color (green to red). The multichannel radiation process was further elucidated by transient absorption and theoretical calculations, benefiting for the application in anti-counterfeiting systems.

Metal-Phenolic Network-Facilitated "Foe-to-Friend" Conversion of Melittin for Cancer Immunotherapy with Boosted Abscopal Effect.

As a naturally occurring cytolytic peptide, melittin (Mel) has strong cytolytic activity and is a potent therapeutic peptide for cancer therapy. However, the serious hemolytic activity of Mel largely impedes its clinical applications. In this work, based on the strong interactions between proteins/peptides and polyphenols, we develop a tannic acid-Fe3+ metal-phenolic network (MPN)-based strategy that can convert Mel from foe to friend via shielding its positive charges and reducing its hemolytic activity. Besides, an immune adjuvant resiquimod (R848) is also introduced for immunostimulation, affording the final Mel- and R848-coloaded nanodrug. The Mel-caused membrane disruption can induce immunogenic cell death for immunostimulation, R848 can act as an immune adjuvant to further facilitate the immunostimulatory effect, and the tannic acid-Fe3+ MPN-mediated Fenton reaction can produce reactive oxygen species for cancer treatment. Further experiments reveal that the nanodrug can effectively cause immunogenic cell death of tumor cells and arouse robust intratumoral and systemic antitumor immunostimulation. In the bilateral tumor-bearing mouse models, the nanodrug considerably destroys the primary tumor and also boosts the abscopal effect to ablate the distant tumor. Collectively, the MPN-facilitated "foe-to-friend" strategy may promote the practical applications of Mel and foster the development of cancer immunotherapeutics.

Analysis of intraoral microvascular anastomosis in maxillofacial defects reconstruction.

This review summarizes the research progress in the field of intraoral microvascular anastomosis techniques (IAT) and attempts to investigate the indications for procedures in which IAT can be applied, the surgical procedure and the difficulties involved, technical assessments, result evaluation and the perspective. Currently, microvascular anastomosis technique is widely used in maxillofacial defects reconstruction from various causes including cutaneous injury or congenital deformity which usually required extensive flap reconstruction and therefore a vascular free flap is routinely used. Conventional microvascular anastomosis reconstruction techniques cannot avoid new incisions, which will affect the postoperative aesthetic situation. Surgeons have therefore attempted to improve this technique to effectively eliminate scars caused by surgery: some patients can be chosen to undergo microvascular anastomosis of the free flap intraorally, thus reducing the extraoral incision caused by the anastomosis located in neck or maxillofacial improving the postoperative appearance of the patients. In addition to preserving the external appearance, intraoral anastomosis technique (IAT) can also solve some other problems of maxillofacial vascular anastomosis, such as insufficient vessel pedicle length and high risk of facial nerve injury.

Interplay of Dual-Proton Transfer Relay to Achieve Full-Color Panel Luminescence in Excited-State Intramolecular Proton Transfer (ESIPT) Fluorophores.

A new design was applied for the facile synthesis of pure organic photoluminescent molecules with dual excited-state intramolecular proton transfer (ESIPT) sites. In this novel class of emitters, full-color panel emission from blue, green, and yellow to red, including white light, can be achieved in different solvents as modulated by the enol-keto(1st)-keto(2nd) tautomer emissions. A comprehensive transient photophysical study verifies that keto(1st) and keto(2nd) have a precursor (<0.8 ps)-successor (∼20 ps)-relayed absorbance relationship, and then a fast equilibrium between the two is established, resulting in dual emissions in the nanosecond scale (∼1900 ps). Through the research on copper ions' selective PL response, the dual-ESIPT mechanism was further verified; in addition, the study of solid-state PL changes upon the stimulus of organic vapor manifests the potential application sensitivity of the molecules as dual-ESIPT sensors. Theoretical results including reaction potential energy surface analyses manifest the fact that dual-proton transfer goes along a sequential route with a smaller energy barrier, firmly supporting the experimental results. An intrinsic system that undergoes intramolecular double proton relayed transfer is thus established for the achievement of much broadened optical responses and full-color display, providing reference for the design and application of advanced dual-ESIPT optical materials.

Phenotype transition of fibroblasts incorporated into patient-derived oral carcinoma organoids.

OBJECTIVE: Cancer-associated fibroblasts (CAFs) are abundantly infiltrated in oral squamous cell carcinoma (OSCC), but the contact-dependent mechanisms that regulate CAFs phenotype in precursor cells, such as paracancerous fibroblasts (PFs), remain unclear. Here, a fibroblast-attached organoid (FAO) model was initiated to determine phenotype transition of fibroblasts triggered by contact with OSCC. MATERIAL AND METHODS: Organoids and fibroblasts were generated using OSCC and adjacent tissues. Cell-clusters containing fibroblasts and tumour cells were aggregated to allow for FAOs expansion. Immunoblotting assay was performed to compare expression of Notch intracellular domain (NICD) in CAFs and PFs. Colony formation assay was employed to evaluate morphological activation of fibroblasts. RESULTS: Compared to traditional 3D co-culture, FAOs better modulated the spatial distribution of fibroblasts with tumour nests. The presence of CAFs with multiple branches was stably observed in FAOs during serial passage. Incorporation with organoids promoted the ability of PFs to form multiple branches. Immunoblotting assay confirmed higher NICD level in CAFs than PFs. Treatment with Notch inhibitor, N-[N-(3, 5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (i.e. DAPT) blocked morphological activation of fibroblasts incorporated into FAO. CONCLUSION: We developed a robust strategy to study contact-dependent mechanisms underlying tumour-stromal interaction, and suggested that Notch activity contributes to biogenesis of OSCC-associated fibroblasts.

Zoning laminectomy for the treatment of ossification of the thoracic ligamentum flavum.

OBJECTIVE: Spinal cord injury is a common occurrence during spinal surgery. In this study, we proposed a zoning laminectomy, which could reduce the incidence of nerve injury. We also discussed the safety and clinical efficacy of the zoning laminectomy for thoracic ossification of the ligamentum flavum (TOLF). METHODS: Forty-five patients with TOLF who underwent zoning laminectomy from October 2016 to February 2020 were included in the retrospective analysis. The Japan Orthopedic Association (JOA) score was used to evaluate clinical outcomes. Meanwhile, the occurrence of complications was recorded. RESULTS: All 45 patients underwent the operation successfully, and the mean follow-up period was 25.3 months, the mean operation time was 160.2 min, the average blood loss was 474.2 ml, and the average hospital time was 8.0 days. At the final evaluation, the JOA score was significantly higher than the preoperative JOA score (P < 0.001) and the overall recovery rate of the JOA score averaged 69.6%. Seventeen patients were graded as excellent, twenty-six as good, and two as fair. The complications included dural tears in nine patients (20.0%), cerebrospinal fluid leakage in seven patients (15.6%), deep infection in one patient (2.2%), and epidural hematoma in one patient (2.2%). All patients recovered well after treatment. Besides, there was no neurological deterioration and thoracic kyphosis occurred. CONCLUSIONS: Zoning laminectomy adopts a phased resection from "safe zone" to "danger zone" and defines the safe removal range of the lamina, which reduces the risks of spinal cord injury caused by instrument manipulation. Therefore, it is a safe and effective surgical option.

Deep learning assisted contrast-enhanced CT-based diagnosis of cervical lymph node metastasis of oral cancer: a retrospective study of 1466 cases.

OBJECTIVES: Lymph node (LN) metastasis is a common cause of recurrence in oral cancer; however, the accuracy of distinguishing positive and negative LNs is not ideal. Here, we aimed to develop a deep learning model that can identify, locate, and distinguish LNs in contrast-enhanced CT (CECT) images with a higher accuracy. METHODS: The preoperative CECT images and corresponding postoperative pathological diagnoses of 1466 patients with oral cancer from our hospital were retrospectively collected. In stage I, full-layer images (five common anatomical structures) were labeled; in stage II, negative and positive LNs were separately labeled. The stage I model was innovatively employed for stage II training to improve accuracy with the idea of transfer learning (TL). The Mask R-CNN instance segmentation framework was selected for model construction and training. The accuracy of the model was compared with that of human observers. RESULTS: A total of 5412 images and 5601 images were labeled in stage I and II, respectively. The stage I model achieved an excellent segmentation effect in the test set (AP50-0.7249). The positive LN accuracy of the stage II TL model was similar to that of the radiologist and much higher than that of the surgeons and students (0.7042 vs. 0.7647 (p = 0.243), 0.4216 (p < 0.001), and 0.3629 (p < 0.001)). The clinical accuracy of the model was highest (0.8509 vs. 0.8000, 0.5500, 0.4500, and 0.6658 of the Radiology Department). CONCLUSIONS: The model was constructed using a deep neural network and had high accuracy in LN localization and metastasis discrimination, which could contribute to accurate diagnosis and customized treatment planning. KEY POINTS: • Lymph node metastasis is not well recognized with modern medical imaging tools. • Transfer learning can improve the accuracy of deep learning model prediction. • Deep learning can aid the accurate identification of lymph node metastasis.

Abdominal core muscle strength training in badminton players / Treinamento de força muscular do centro abdominal nos jogadores de badminton / Entrenamiento de la fuerza muscular del núcleo abdominal en jugadores de bádminton

ABSTRACT Introduction: Badminton is a sport of intense confrontation and variable transitions between attack and defense, where the athlete maintains an extreme body dynamic. Objective: Study the effects of abdominal core muscle strength training on badminton players. Methods: A screening method was used by randomly selecting 20 male badminton players. The effects of abdominal core muscle strength training and the athletes' specific skills were evaluated by a protocol after 10 weeks of strength training. Results: The results of the two groups were significantly different by t-test, p<0.05. Both improved in all indicators. The experimental group showed higher scores in 6 indicators than the control group, with p<0.01 having a highly significant difference. Conclusion: Abdominal core muscle strength training can effectively improve body stability, optimize the technical movements of badminton players, and play a positive role in body stability. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: O badminton é um esporte de intenso confronto e transições entre ataque e defesa variáveis, onde o atleta mantém uma extrema dinâmica corporal. Objetivo: Estudar os efeitos do treinamento de força muscular do centro abdominal nos jogadores de badminton. Métodos: Foi utilizado um método de triagem selecionando aleatoriamente 20 jogadores masculinos de badminton. Os efeitos do treinamento de força muscular do centro abdominal e as habilidades específicas dos atletas foram avaliados por um protocolo após 10 semanas de treinamento de força. Resultados: Os resultados dos dois grupos foram significativamente diferentes pelo teste t, p<0,05. Ambos melhoraram em todos os indicadores, o grupo experimental apresentou pontuações mais altas em 6 indicadores do que o grupo controle, com p<0,01 tendo uma diferença altamente significativa. Conclusão: O treinamento de força muscular do centro abdominal na área central pode melhorar efetivamente a estabilidade corporal e otimizar os movimentos técnicos dos jogadores de badminton, além de desempenhar um papel positivo na estabilidade corporal. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: El bádminton es un deporte de intensa confrontación y transiciones variables entre el ataque y la defensa, donde el deportista mantiene una dinámica corporal extrema. Objetivo: Estudiar los efectos del entrenamiento de la fuerza muscular del núcleo abdominal en jugadores de bádminton. Métodos: Se utilizó un método de cribado seleccionando aleatoriamente a 20 jugadores de bádminton de sexo masculino. Los efectos del entrenamiento de la fuerza del núcleo abdominal y las habilidades específicas de los atletas se evaluaron mediante un protocolo después de 10 semanas de entrenamiento de la fuerza. Resultados: Los resultados de los dos grupos fueron significativamente diferentes mediante la prueba t, p<0,05. Ambos mejoraron en todos los indicadores, el grupo experimental mostró puntuaciones más altas en 6 indicadores que el grupo de control, con p<0,01 teniendo una diferencia altamente significativa. Conclusión: El entrenamiento de la fuerza muscular del núcleo abdominal puede mejorar eficazmente la estabilidad corporal y optimizar los movimientos técnicos de los jugadores de bádminton, y desempeñar un papel positivo en la estabilidad corporal. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Roles of Mitochondria in Oral Squamous Cell Carcinoma Therapy: Friend or Foe?

Oral squamous cell carcinoma (OSCC) therapy is unsatisfactory, and the prevalence of the disease is increasing. The role of mitochondria in OSCC therapy has recently attracted increasing attention, however, many mechanisms remain unclear. Therefore, we elaborate upon relative studies in this review to achieve a better therapeutic effect of OSCC treatment in the future. Interestingly, we found that mitochondria not only contribute to OSCC therapy but also promote resistance, and targeting the mitochondria of OSCC via nanoparticles is a promising way to treat OSCC.

In situ generation of micrometer-sized tumor cell-derived vesicles as autologous cancer vaccines for boosting systemic immune responses.

Cancer vaccine, which can promote tumor-specific immunostimulation, is one of the most important immunotherapeutic strategies and holds tremendous potential for cancer treatment/prevention. Here, we prepare a series of nanoparticles composed of doxorubicin- and tyrosine kinase inhibitor-loaded and hyaluronic acid-coated dendritic polymers (termed HDDT nanoparticles) and find that the HDDT nanoparticles can convert various cancer cells to micrometer-sized vesicles (1.6-3.2 µm; termed HMVs) with ~100% cell-to-HMV conversion efficiency. We confirm in two tumor-bearing mouse models that the nanoparticles can restrain tumor growth, induce robust immunogenic cell death, and convert the primary tumor into an antigen depot by producing HMVs in situ to serve as personalized vaccines for cancer immunotherapy. Furthermore, the HDDT-healed mice show a strong immune memory effect and the HDDT treatment can realize long-term protection against tumor rechallenge. Collectively, the present work provides a general strategy for the preparation of tumor-associated antigen-containing vesicles and the development of personalized cancer vaccines.

The influence of variation in altitude on athletic performance in long-distance runners / Influência da variação de altitude no desempenho atlético em corredores de longa distância / Influencia de la variación de la altitud en el rendimiento atlético de los corredores de larga distancia

ABSTRACT Introduction: The academic community has demonstrated the link of athletic performance in track and field with critical factors of sports training, including the psychology of competition. Recently, research has been verified that athletic performance is also related to altitude, weather, ambiance, and the timing of the competition. There are no studies to provide theoretical and practical training experience in the regional environment of Ganzhou. Objective: This paper analyzes the influence of altitude training in professional performance athletes. Concurrently, analysis of the physiological and biochemical indicators of the athletes is performed. Methods: Several long-distance runners had an 8-week altitude training. Analyzed the physiological and biochemical indicators of the athletes before and after the training. At the same time, perform mathematical-statistical analysis on the performance of long-distance runners before and after training. Results: After altitude training, hemoglobin and red blood cells showed a significant decrease (P<0.01). After training, athletes' performance improved considerably (P<0.01). Conclusion: Training at different altitudes may promote an ascending curve in the athletes' performance until a plateau in the fourth week of training. Evidence Level II; Therapeutic Studies - Investigating the result.

RESUMO Introdução: A comunidade acadêmica tem demonstrado a ligação do desempenho em pistas e campo com os principais fatores de treinamento esportivo, incluindo a psicologia da competição. Em pesquisas recentes, foi verificado que o nível do desempenho atlético também está relacionado à altitude, ao clima, ao ambiente do local e ao cronograma da competição. Até o momento não existem estudos para proporcionar experiência teórica e prática de treinamento no ambiente regional de Ganzhou. Objetivo: Este artigo analisa a influência do treinamento em altitude sobre o desempenho dos profissionais de atletismo. Ao mesmo tempo, analisamos os indicadores fisiológicos e bioquímicos dos atletas. Métodos: Vários corredores de longa distância tiveram um treinamento de altitude de ٨ semanas. Analisamos os indicadores fisiológicos e bioquímicos dos atletas antes e depois do treinamento. Ao mesmo tempo, realiza análises matemáticas-estatísticas sobre o desempenho dos corredores de longa distância, antes e depois do treinamento. Resultados: Após o treinamento de altitude, a hemoglobina e os glóbulos vermelhos apresentaram diminuição significativa (P<0,01). Após o treinamento, o desempenho dos atletas melhorou consideravelmente (P<0,01). Conclusão: O treinamento em diferentes altitudes pode promover uma curva ascendente no desempenho dos atletas até seu platô, na quarta semana de treino. Nível de evidência II; Estudos Terapêuticos - Investigação de Resultados.

RESUMEN Introducción: La comunidad académica ha demostrado la relación del rendimiento deportivo en el atletismo con los principales factores del entrenamiento deportivo, incluida la psicología de la competición. En investigaciones recientes, se ha descubierto que el nivel de rendimiento deportivo también está relacionado con la altitud, el clima, el entorno del lugar y el horario de la competición. Hasta la fecha, no existen estudios que proporcionen una experiencia de formación teórica y práctica en el entorno regional de Ganzhou. Objetivo: Este trabajo analiza la influencia del entrenamiento en altitud en el rendimiento de los atletas profesionales de atletismo. Al mismo tiempo, analizamos los indicadores fisiológicos y bioquímicos de los atletas. Métodos: Varios corredores de larga distancia se sometieron a un entrenamiento en altitud de 8 semanas. Analizamos los indicadores fisiológicos y bioquímicos de los atletas antes y después del entrenamiento. Al mismo tiempo, realice un análisis matemático-estadístico sobre el rendimiento de los corredores de fondo antes y después del entrenamiento. Resultados: Tras el entrenamiento en altitud, la hemoglobina y los glóbulos rojos mostraron un descenso significativo (P<0,01). Tras el entrenamiento, el rendimiento de los atletas mejoró considerablemente (P<0,01). Conclusión: El entrenamiento en diferentes altitudes puede promover una curva ascendente en el rendimiento de los atletas hasta su meseta, en la cuarta semana de entrenamiento. Nivel de evidencia II; Estudios terapéuticos - Investigación de resultados.

Cancer cells corrupt normal epithelial cells through miR-let-7c-rich small extracellular vesicle-mediated downregulation of p53/PTEN.

Tumor volume increases continuously in the advanced stage, and aside from the self-renewal of tumor cells, whether the oncogenic transformation of surrounding normal cells is involved in this process is currently unclear. Here, we show that oral squamous cell carcinoma (OSCC)-derived small extracellular vesicles (sEVs) promote the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of normal epithelial cells but delay their apoptosis. In addition, nuclear-cytoplasmic invaginations and multiple nucleoli are observed in sEV-treated normal cells, both of which are typical characteristics of premalignant lesions of OSCC. Mechanistically, miR-let-7c in OSCC-derived sEVs is transferred to normal epithelial cells, leading to the transcriptional inhibition of p53 and inactivation of the p53/PTEN pathway. In summary, we demonstrate that OSCC-derived sEVs promote the precancerous transformation of normal epithelial cells, in which the miR-let-7c/p53/PTEN pathway plays an important role. Our findings reveal that cancer cells can corrupt normal epithelial cells through sEVs, which provides new insight into the progression of OSCC.