Acidity-responsive polyphenol-coordinated nanovaccines for improving tumor immunotherapy via bidirectional reshaping of the immunosuppressive microenvironment and controllable release of antigens.

The tumor immunosuppressive microenvironment (TIME) and uncontrollable release of antigens can lower the efficacy of nanovaccine-based immunotherapy (NBI). Therefore, it is necessary to develop a new strategy for TIME reshaping and controllable release of antigens to improve the NBI efficacy. Herein, an acidity-responsive Schiff base-conjugated polyphenol-coordinated nanovaccine was constructed for the first time to realize bidirectional TIME reshaping and controllable release of antigens for activating T cells. In particular, an acidity-responsive tannic acid-ovalbumin (TA-OVA) nanoconjugate was prepared via a Schiff base reaction. FeIII was coordinated with TA-OVA to produce a FeIII-TA-OVA nanosystem, and 1-methyltryptophan (1-MT) as an indoleamine 2,3-dioxygenase inhibitor was loaded to form a polyphenol-coordinated nanovaccine. The coordination between FeIII and TA could cause photothermal ablation of primary tumors, and the acidity-triggered Schiff base dissociation of TA-OVA could controllably release OVA to realize lysosome escape, initiating the body's immune response. More importantly, oxidative stress generated by a tumor-specific Fenton reaction of Fe ions could promote the polarization of tumor-associated macrophages from the M2 to M1 phenotype, resulting in the upregulation of cytotoxic T cells and helper T cells. Meanwhile, 1-MT could downregulate immunosuppressive regulatory T cells. Overall, such skillful combination of bidirectional TIME reshaping and controllable antigen release into one coordination nanosystem could effectively enhance the NBI efficacy of tumors.

A qualitative exploration of fear of progression in patients with nasopharyngeal carcinoma treated with proton and heavy ion therapy.

OBJECTIVE: To investigate fear of progression (FOP) in nasopharyngeal carcinoma (NPC) patients treated with proton and heavy ion therapy. METHODS: Thirty NPC patients were selected for face-to-face semistructured interviews through purposive sampling while using the phenomenological approach in qualitative research. The interviews were transcribed, organized, and analyzed by applying Colaizzi's seven-step analysis. RESULTS: Seven themes were summarized, namely, illness uncertainty, trapped into insecurity (including four categories: insecurity about the possibility of discrimination, insecurity about the possibility of the inability to tolerate the pain of retreatment, insecurity about the difficulty of retreatment after recurrence, and insecurity of waiting for test results), hopelessness, loss, guilt toward children, enhancing tolerance toward family, and self-emotional comfort. CONCLUSION: We found that women with children and patients who experienced their first episode underwent significant FOP. Patients at the postgraduate level and above were more inclined to feel loss. The finding that respondents expressed is intense FOP while waiting for test results, which provides a reference for the analysis of the trajectory of FOP. Health care professions should be cognitively aware the importance of eliminating patients' uncertainty and insecurity about disease to enhance their positive experience in coping with cancer.

Exploring the experience of meaning-centered group psychotherapy among Chinese cancer patients during active treatment: a descriptive qualitative study.

Objective: Meaninglessness poses a significant psychological challenge for cancer patients, negatively affecting their quality of life and increasing the risk of suicide. Meaning-Centered Group Therapy (MCGP) is an intervention designed specifically to enhance the meaning of life of cancer patients. Extensive research has documented its effectiveness across various cultures and populations. However, limited research has been conducted on the subjective experiences and perspectives of participants engaged in MCGP. Thus, the purpose of this study was to employ a qualitative design to explore the experiences and viewpoints of Chinese cancer patients who have undergone MCGP. Methods: Within a two-week timeframe following the conclusion of MCGP, semi-structured interviews were administered to twenty-one participants who had engaged in the therapy. The interview data were transcribed and subjected to thematic analysis. Results: Four main themes were identified: (a) Self-perceived personal change, (b) Overall experience of group therapy, (c) Barriers to participation of MCGP, and (d) Suggestions for future interventions. Conclusion: Despite the barriers to participation in the MCGP process, the overall experience for Chinese cancer patients undergoing active treatment is valuable and positive, providing multiple benefits. Future studies could explore the adaptation of MCGP to a broader range of cancer populations and diverse study populations.

Trajectories of fear of progression in nasopharyngeal carcinoma patients receiving proton and heavy ion therapy.

OBJECTIVE: The study examined the growth trajectory of fear of progression(FOP) in nasopharyngeal carcinoma (NPC) patients. In addition, sociodemographic and clinical variables of each trajectory class were analyzed. METHOD: Two hundred sixteen NPC patients undergoing proton and heavy ion therapy were measured beginning (T0) and end of a 4-week proton and heavy ion therapy (T1), 3 months (T2) and 6 months (T3) after discharge. And data from the final 197 NPC patients were analyzed. NPC patients' FOP was investigated by the Fear of Progression Questionnaire-Short Form (FOP-Q-SF) form T0 to T3. SPSS and Mplus were used for statistical analysis. The LGMM was used to analyze the trajectory of FOP followed up over 6 months after proton and heavy ion therapy. The logistic regression was utilized to compare the differences in sociodemographic and clinical characteristics of patients in different trajectory groups of FOP. RESULTS: One hundred ninety-seven NPC patients were analyzed. LGMM analysis showed that three-group trajectory solution was the best fitting (low-fear decline FOP (14.21%), the moderate-fear stable FOP(43.15%), and high-fear rising FOP (42.64%). Significant positive associations were found between age < 30 years (ß = 3.399, p = 0.023), with or without children (ß = 3.1, p = 0.002), primary/recurrence (ß = -6.196, p < 0.001), diagnosis < 3 months (ß = 4.435, p = 0.031), high school education (ß = 2.98, p = 0.048), and high fear rising FOP. Patients who had moderate financial stress (ß = 2.51, p = 0.041), with or without children (ß = 1.564, p = 0.003), primary/recurrence (ß = -2.578, p = 0.005), less than 30 radiotherapy times (ß = 0.979, p = 0.046) tended to report significant moderate-fear stable FOP over time. CONCLUSION: 42.64% of the NPC patients showed high-fear rising FOP over the 6 months after treatment. Age 18-30 years, with or without children, relapsed, diagnosis < 3 months, and high school education and reporting being a pessimist predicts higher FOP scores. Early identification of age 18-30 years, with or without children, relapsed, diagnosis < 3 months, and high school education might help to identify populations experiencing long-term FOP. Clinical teams responsible to develop the target interventions for management of FCR in clinical practice.

Efficacy of meaning-centered group psychotherapy in Chinese patients with cancer: A randomized controlled trial.

OBJECTIVES: Meaninglessness is one of the most common psychological problems in cancer patients, which can lead to anxiety, depression and psychological distress, and diminished quality of life. Recent evidence indicates that meaning-centered group psychotherapy (MCGP) effectively enhances the meaning in life among cancer patients. This study aimed to evaluate the impact of MCGP on the meaning in life, post-traumatic growth, psychological distress, and fear of recurrence among Chinese cancer patients with a favorable prognosis. METHODS: Sixty-six cancer patients were randomly assigned to either the MCGP group (n = 33) or the control group (n = 33). Participants in the MCGP group underwent a 4-week, 8-session MCGP, while those in the control group received usual care. Meaning in life, post-traumatic growth, psychological distress, and fear of recurrence were assessed at both baseline and postintervention to evaluate the impact of the intervention. The intervention outcomes were analyzed using paired t-tests or analysis of covariance, as appropriate. RESULTS: Patients in the MCGP group demonstrated significant improvements in meaning in life, post-traumatic growth, and fear of recurrence from baseline to postintervention. In comparison to the control group, the MCGP group displayed positive effects on meaning in life and post-traumatic growth following the intervention. However, no significant effects were observed in terms of psychological distress and fear of recurrence. SIGNIFICANCE OF RESULTS: Our research offers evidence supporting the effectiveness of MCGP in enhancing meaning in life and post-traumatic growth among Chinese cancer patients with a favorable prognosis.

Latent profiles of resilience and associations with quality of life in head and neck cancer patients undergoing proton and heavy ion therapy.

Background: Psychological resilience is the most important psychological protection factor for cancer patients in the face of tumors and treatment. However, few studies have performed meaningful latent profile analyses of resilience to identify unobserved subgroups of head and neck cancer patients. Purpose: The purpose of this study was to investigate the characteristics of resilience in head and neck cancer patients using latent profile analysis (LPA) to determine the sociodemographic and disease characteristics of each profile. In particular, we examined the association of different resilience profiles with the quality of life of head and neck cancer patients. Methods: A total of 254 head and neck cancer patients completed a demographic questionnaire, the Resilience Scale Specific to Cancer and the EOTRC QLQ-C3O, used to assess their resilience and quality of life. Results: LPA identified three distinct profiles based on varying levels of resilience: "low resilience" group (n = 45; 17.72%), "moderate resilience" group (n = 113; 44.49%), and "high resilience" group (n = 96; 37.80%). Gender (χ2 = 6.20; p < 0.01), education level (χ2 = 1,812.59; p < 0.01), treatment regimen (χ2 = 6.32; p < 0.01), tumor stage (χ2 = 3.92; p ≤ 0.05), and initial recurrence (χ2 = 5.13; p < 0.05) were important predictors. High resilience was significantly related to higher quality of life (χ2 = 15.694; p < 0.001). Conclusions: Head and neck cancer patients' psychological resilience can be categorized as three resilience profiles; those who are female and have a low education level tend to have lower psychological resilience. Low resilience in patients is linked to poor role function and social function, low quality of life, and more severe pain symptoms, highlighting the need to address resilience in patient care for improved wellbeing.

TLR4 inhibition suppresses growth in oestrogen-induced prolactinoma models.

Prolactinomas have harmful effects on human health. Bromocriptine is the only commercially available drug in China, but about 25% of prolactinoma patients do not respond to it in clinic, its pathogenesis remains unknown. Thus, its pathogenesis needs to be determined to develop new therapeutic methods for prolactinomas. The expression of ERß, TLR4, and prolactin (PRL) in the pituitary gland of C57BL/6 mice and human prolactinoma specimen was examined by immunofluorescence or immunohistochemistry. The role of TLR4 in prolactinoma was determined using estradiol-induced models of C57BL/6 wild-type and TLR4-/- mice. MMQ cells were treated with estradiol, fulvestrant, and lipopolysaccharide (LPS) or transfected with TLR4 siRNA to study the expression of ERß, TLR4, and PRL in these cells. Furthermore, the interaction between ERß and TLR4 was investigated by immunoprecipitation analysis. The expression of PRL and TLR4 was co-located and increased in the pituitary gland of mice and human prolactinoma specimen compared to that in the control specimen. Meanwhile, TLR4 knockout or treatment with the TLR4 inhibitor TAK242 not only significantly inhibited tumor overgrowth but also decreased the expression of PRL in estradiol-treated mice through p38 MAPK pathway regulation. However, MMQ treated with estradiol and LPS enhanced PRL expression than treated with estradiol or LPS alone. Finally, ERß or TLR4 inhibition prevented the estradiol-induced PRL increase by regulating the TLR4/p38 MAPK pathway in vitro. Estradiol promoted prolactinoma development by activating the TLR4/p38 MAPK pathway through ERß, and TLR4 is a potential therapeutic target for prolactinoma treatment.

The role of MAPK11/12/13/14 (p38 MAPK) protein in dopamine agonist-resistant prolactinomas.

BACKGROUND: Prolactinoma is a functional pituitary adenoma that secretes excessive prolactin. Dopamine agonists (DAs) such as bromocriptine (BRC) are the first-line treatment for prolactinomas, but the resistance rate is increasing year by year, creating a clinical challenge. Therefore, it is urgent to explore the molecular mechanism of bromocriptine resistance in prolactinomas. Activation of the P38 MAPK pathway affects multidrug resistance in tumours. Our previous studies have demonstrated that inhibiting MAPK14 can suppress the occurrence of prolactinoma, but the role of MAPK11/12/13/14 (p38 MAPK) signalling in dopamine agonist-resistant prolactinomas is still unclear. METHODS: A prolactinoma rat model was established to determine the effect of bromocriptine on MAPK11/12/13/14 signalling. DA-resistant GH3 cells and DA-sensitive MMQ cells were used, and the role of MAPK11/12/13/14 in bromocriptine-resistant prolactinomas was preliminarily verified by western blot, RT-qPCR, ELISA, flow cytometry and CCK-8 experiments. The effects of MAPK11 or MAPK14 on bromocriptine-resistant prolactinomas were further verified by siRNA transfection experiments. RESULTS: Bromocriptine was used to treat rat prolactinoma by upregulating DRD2 expression and downregulating the expression level of MAPK11/12/13/14 in vivo experiments. The in vitro experiments showed that GH3 cells are resistant to bromocriptine and that MMQ cells are sensitive to bromocriptine. Bromocriptine could significantly reduce the expression of MAPK12 and MAPK13 in GH3 cells and MMQ cells. Bromocriptine could significantly reduce the expression of MAPK11, MAPK14, NF-κB p65 and Bcl2 in MMQ but had no effect on MAPK11, MAPK14, NF-κB p65 and Bcl2 in GH3 cells. In addition, knockdown of MAPK11 and MAPK14 in GH3 cells by siRNA transfection reversed the resistance of GH3 cells to bromocriptine, and haloperidol (HAL) blocked the inhibitory effect of bromocriptine on MAPK14, MAPK11, and PRL in MMQ cells. Our findings show that MAPK11 and MAPK14 proteins are involved in bromocriptine resistance in prolactinomas. CONCLUSION: Bromocriptine reduces the expression of MAPK11/12/13/14 in prolactinomas, and MAPK11 and MAPK14 are involved in bromocriptine resistance in prolactinomas by regulating apoptosis. Reducing the expression of MAPK11 or MAPK14 can reverse bromocriptine resistance in prolactinomas.

PBK/TOPK Inhibitor Suppresses the Progression of Prolactinomas.

Background: Prolactinoma is the most common type of pituitary tumors, and its resultant tumor occupying and hormone disturbance greatly damage the health of patients. In this study, we investigated a protein kinase-PDZ Binding Kinase (PBK)/T-LAK Cell-Originated Protein Kinase (TOPK) as a candidate protein regulating prolactin (PRL) secretion and tumor growth of prolactinomas. Methods: Downloaded prolactinoma transcriptome dataset from Gene Expression Omnibus (GEO) database, and screened differentially expressed genes (DEGs) between normal pituitary tissues and prolactinoma tissues. Then, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of DEGs were performed, a protein-protein interaction (PPI) network was constructed and the hub genes were identified. After a literature search, TOPK was presumed as an candidate target regulating the prolactinoma. We found a specific inhibitor of TOPK to investigate its effects on the proliferation, migration, apoptosis and PRL secretion of pituitary tumor cells. Finally, the regulation of TOPK inhibitor on its downstream target-p38 Mitogen Activated Protein Kinase (p38 MAPK) was detected to explore the potential mechanism. Results: A total of 361 DEGs were identified, and 20 hub genes were screened out. TOPK inhibitor HI-TOPK-032 could suppress the proliferation & migration and induce apoptosis of pituitary tumor cells in vitro, and reduce PRL secretion and tumor growth in vivo. HI-TOPK-032 also inhibited the phosphorylation level of the downstream target p38 MAPK, suggesting that TOPK inhibitors regulate the development of prolactinoma by mediating p38 MAPK. Conclusion: Our study of identification and functional validation of TOPK suggests that this candidate can be a promising molecular target for prolactinoma treatment.

Cellulose nanocrystals mediated assembly of graphene in rubber composites for chemical sensing applications.

In this study, we report a green assembled approach to prepare natural rubber (NR) composites with 3D interconnected graphene-based conductive networks. Taking advantage of the water-dispersity and amphiphilicity of cellulose nanocrystals (CNC), well suspended graphene@CNC aqueous colloids could be prepared by the CNC-mediated reduction of graphene oxide. When homogenized with NR latex under ultrasonication and subsequently co-coagulation, the graphene@CNC nanohybrids selectively located in the interstitial space between the NR latex microspheres and constructed an ordered 3D conductive structure. This unique 3D conductive network endowed the NR composites with remarkably enhanced electric conductivity (the percolation threshold is twofold lower than that of the conventional NR/graphene composites), mechanical properties and more importantly resistivity response to organic liquids. Our strategy offered a novel, simple and eco-friendly route for the fabrication of liquid sensors capable of sensing and discriminating various solvent leakage in chemical industry as well as environmental monitoring.

Tailoring percolating conductive networks of natural rubber composites for flexible strain sensors via a cellulose nanocrystal templated assembly.

Conductive polymer composites (CPCs) just above the percolation threshold exhibit a unique strain-reversible electric response upon application of tensile strain, which can be used to prepare strain sensors. However, it is difficult to balance the electric conductivity which is fundamental to a stable output signal and the strain sensing sensitivity due to the relatively dense conductive pathways of the traditional CPCs. Constructing a "brittle" but effective conductive network structure in CPCs is the essential foundation of a desirable sensing material. Here, we demonstrate for the first time that highly flexible, stretchable, sensitive, and reversible strain sensors can be fabricated by a facile latex assembly approach, in which nontoxic, sustainable and biodegradable cellulose nanocrystals played a key role in tailoring the percolating network of conductive natural rubber (NR)/carbon nanotube (CNT) composites. The resulting nanocomposites with a continuous 3D conductive structure exhibited a very low electrical conductivity percolation threshold (4-fold lower than that of the conventional NR/CNT composites), high resistivity and sensitivity (gauge factor ≈ 43.5) and meanwhile good reproducibility of up to 100% strain. The proposed materials and principles in this study open up a novel practical approach to design high performance flexible sensors for a broad range of multifunctional applications.

Preparation and microwave absorbing properties of carbon/cobalt ferromagnetic composites.

Carbon/cobalt ferromagnetic light composites with high performance of microwave absorbing properties were prepared by hydrothermal method using starch and hollow cobalt ferrites. It was concluded that after carbonization the spinel structure ferrites changed to Co3Fe7 alloys and the temperature of graphitization was significantly decreased for the catalytic of CoFe2O4/Co3Fe7. The increase of carbon content, and exist of CoFe2O4/Co3Fe7 heightened the microwave absorbing properties. Electromagnetic parameters were tested with 40% of the titled materials and 60% of paraffin wax composites by using HP8722ES vector network analyzer. The reflection was also simulated through transmission line theory. The microwave absorbers exhibited a maximum reflection loss -43 dB and the electromagnetic wave absorption less than -10 dB was found to exceed 3.0 GHz between 11.6 GHz and 15 GHz for an absorber thickness of 2 mm.