Decreased Treg cells induced by bisphenol A is associated with up-regulation of PI3K/Akt/mTOR signaling pathway and Foxp3 DNA methylation in spleen of adolescent mice.

The current study aimed to explore whether bisphenol A (BPA) exposure aggravated the decrease in Tregs induced by ovalbumin (OVA) in adolescent female mouse models of asthma, and whether the process was associated with mTOR-mediated signaling pathways and DNA methylation levels. A total of 40 female C57BL/6 mice at the age of four weeks were used and divided into five groups after 1 week of domestication. Each group consisted of eight mice: the control group, OVA group, OVA + BPA (0.1 µg mL-1) group, OVA + BPA (0.2 µg mL-1) group, and OVA + BPA (0.4 µg mL-1) group. Results revealed that Foxp3 protein levels decreased in the spleens of mice exposed to BPA compared to those in the OVA group. After an elevation in BPA dose, the mRNAs of methyltransferases (Dnmt1, Dnmt3a, and Dnmt3b) were gradually upregulated. The mechanism was related to the activity of TLR4/NF-κB and PI3K/Akt/mTOR signaling pathways and the enhancement of Foxp3 DNA methylation. Our results, collectively, provided a new view for studying the mechanisms underlying BPA exposure-induced immune dysfunction. Investigation of the regulatory mechanisms of DNA methylation in the abnormal Th immune response caused by BPA exposure could help reveal the causes and molecular mechanisms underlying the high incidence of allergic diseases in children in recent years.

A Polymer-Based Antigen Carrier Activates Two Innate Immune Pathways for Adjuvant-Free Subunit Vaccines.

The activation of multiple Pattern Recognition Receptors (PRRs) has been demonstrated to trigger inflammatory responses and coordinate the host's adaptive immunity during pathogen infections. The use of PRR agonists as vaccine adjuvants has been reported to synergistically induce specific humoral and cellular immune responses. However, incorporating multiple PRR agonists as adjuvants increases the complexity of vaccine design and manufacturing. In this study, we discovered a polymer that can activate both the Toll-like receptor (TLR) pathway and cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway. The polymer was then conjugated to protein antigens, creating an antigen delivery system for subunit vaccines. Without additional adjuvants, the antigen-polymer conjugates elicited strong antigen-specific humoral and cellular immune responses. Furthermore, the antigen-polymer conjugates, containing the Receptor Binding Domain (RBD) of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike Protein or the Monkeypox Antigen M1R as the antigens, were found to induce potent antigen-specific antibodies, neutralizing antibodies, and cytotoxic T cells. Immunization with M1R-polymer also resulted in effective protection in a lethal challenge model. In conclusion, this vaccine delivery platform offers an effective, safe, and simple strategy for inducing antigen-specific immunity against infectious diseases.

Cancer pain intensity and perceived social support in palliative care: 1-week prospective study.

OBJECTIVES: Pain is a complex and multidimensional experience affected by psychosocial factors. Perceived social support (PSS) has been considered as a positive psychosocial resource for effective regulation of cancer patients' well-being. Our study examined the relationship between PSS and pain intensity under 1-week palliative care. METHODS: A prospective study was conducted of terminal cancer inpatients (N=84) recruited from the hospice ward. Pain intensity was assessed on admission and 1 week later, and patients completed self-report questionnaires assessing PSS at admission. The repeated designed analysis of variance was used to explore the correlate of PSS with cancer pain. RESULTS: Pain intensity decreased after 1 week (t=2.303, p=0.024), and 47.62% gained pain relief. For pain intensity, there was a significant PSS group×time interaction effect detected (F=4.544, p=0.036). Pain intensity in the high PSS group was significantly reduced 1 week later (p=0.008), while the change of pain intensity was not significant in the low PSS group (p=0.609). CONCLUSIONS: PSS at admission predicted the 1-week development of pain intensity. Identifying PSS of terminal cancer patients leads to early interventions that are more effective in improving pain management of palliative care.

3D Shape-Based Myocardial Infarction Prediction Using Point Cloud Classification Networks.

Myocardial infarction (MI) is one of the most prevalent cardiovascular diseases with associated clinical decision-making typically based on single-valued imaging biomarkers. However, such metrics only approximate the complex 3D structure and physiology of the heart and hence hinder a better understanding and prediction of MI outcomes. In this work, we investigate the utility of complete 3D cardiac shapes in the form of point clouds for an improved detection of MI events. To this end, we propose a fully automatic multi-step pipeline consisting of a 3D cardiac surface reconstruction step followed by a point cloud classification network. Our method utilizes recent advances in geometric deep learning on point clouds to enable direct and efficient multi-scale learning on high-resolution surface models of the cardiac anatomy. We evaluate our approach on 1068 UK Biobank subjects for the tasks of prevalent MI detection and incident MI prediction and find improvements of ∼13% and ∼5% respectively over clinical benchmarks. Furthermore, we analyze the role of each ventricle and cardiac phase for 3D shape-based MI detection and conduct a visual analysis of the morphological and physiological patterns typically associated with MI outcomes.Clinical relevance- The presented approach enables the fast and fully automatic pathology-specific analysis of full 3D cardiac shapes. It can thus be employed as a real-time diagnostic tool in clinical practice to discover and visualize more intricate biomarkers than currently used single-valued metrics and improve predictive accuracy of myocardial infarction.

Boosting with an aerosolized Ad5-nCoV elicited robust immune responses in inactivated COVID-19 vaccines recipients.

Introduction: The SARS-CoV-2 Omicron variant has become the dominant SARS-CoV-2 variant and exhibits immune escape to current COVID-19 vaccines, the further boosting strategies are required. Methods: We have conducted a non-randomized, open-label and parallel-controlled phase 4 trial to evaluate the magnitude and longevity of immune responses to booster vaccination with intramuscular adenovirus vectored vaccine (Ad5-nCoV), aerosolized Ad5-nCoV, a recombinant protein subunit vaccine (ZF2001) or homologous inactivated vaccine (CoronaVac) in those who received two doses of inactivated COVID-19 vaccines. Results: The aerosolized Ad5-nCoV induced the most robust and long-lasting neutralizing activity against Omicron variant and IFNg T-cell response among all the boosters, with a distinct mucosal immune response. SARS-CoV-2-specific mucosal IgA response was substantially generated in subjects boosted with the aerosolized Ad5-nCoV at day 14 post-vaccination. At month 6, participants boosted with the aerosolized Ad5-nCoV had remarkably higher median titer and seroconversion of the Omicron BA.4/5-specific neutralizing antibody than those who received other boosters. Discussion: Our findings suggest that aerosolized Ad5-nCoV may provide an efficient alternative in response to the spread of the Omicron BA.4/5 variant. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=152729, identifier ChiCTR2200057278.

A Rift Valley fever mRNA vaccine elicits strong immune responses in mice and rhesus macaques.

Rift Valley fever virus (RVFV) is listed as a priority pathogen by the World Health Organization (WHO) because it causes serious and fatal disease in humans, and there are currently no effective countermeasures. Therefore, it is urgent to develop a safe and efficacious vaccine. Here, we developed six nucleotide-modified mRNA vaccines encoding different regions of the Gn and Gc proteins of RVFV encapsulated in lipid nanoparticles, compared their ability to induce immune responses in mice and found that mRNA vaccine encoding the full-length Gn and Gc proteins had the strongest ability to induce cellular and humoral immune responses. IFNAR(-/-) mice vaccinated with mRNA-GnGc were protected from lethal RVFV challenge. In addition, mRNA-GnGc induced high levels of neutralizing antibodies and cellular responses in rhesus macaques, as well as antigen-specific memory B cells. These data demonstrated that mRNA-GnGc is a potent and promising vaccine candidate for RVFV.

Dimensions of spiritual well-being in relation to physical and psychological symptoms: a cross-sectional study of advanced cancer patients admitted to a palliative care unit.

OBJECTIVES: Advanced cancer patients face various symptoms, which can cause physical and psychological distress. As a multidimensional construct, spiritual well-being (SWB) may be an inner resource for dealing with these problems. Our study explored the impact of different dimensions of SWB on physical and psychological symptoms in advanced cancer patients admitted to a palliative care unit. METHODS: This cross-sectional study was conducted among 108 advanced cancer patients in the Hospice Ward, Shengjing Hospital of China Medical University. Patients completed questionnaires on SWB and cancer-related symptoms (insomnia, fatigue, pain, depression and anxiety) at the time of admission. Linear regression analysis was applied to determine the relationship between SWB (meaning, peace and faith) and symptom distress. RESULTS: SWB accounted for an additional variance of cancer-related symptoms (17.8% to 44.4%). Meaning was negatively associated with insomnia (ß = -0.516, p < 0.001) and fatigue (ß = -0.563, p < 0.001). Peace and faith were related to lower psychological symptoms, while meaning represented a positive effect on anxiety (ß = 0.275, p = 0.036). Higher peace was associated with lower cancer pain (ß = -0.422, p < 0.001). CONCLUSIONS: Our findings suggested that achieving peace and faith appeared to function consistently as a positive resource for advanced cancer patients on depression, anxiety and pain, while meaning may serve to facilitate or hinder positive adjustment. Future studies should focus on the potential clinical implications by identifying the distinct dimension of SWB as symptom management targets in the palliative care practice.

Precise modification of the surface charge of antigen enhances vaccine immunogenicity.

Aluminum (alum) adjuvant is the most extensively used protein subunit vaccine adjuvant, and its effectiveness and safety have been widely recognized. The surface charge of the antigen determines its electrostatic adsorption to alum adjuvant, which directly affects the immune efficacy of the protein vaccine. In our study, we precisely modified its surface charge by inserting charged amino acids into the flexible region of the SARS-CoV-2 receptor-binding domain (RBD), achieving electrostatic adsorption and a site-specific anchor between the immunogen and alum adjuvant. This innovative strategy extended the bioavailability of the RBD and directionally displayed the neutralizing epitopes, thereby significantly enhancing humoral and cellular immunity. Furthermore, the required dose of antigen and alum adjuvant was greatly reduced, which improved the safety and accessibility of the protein subunit vaccine. On this basis, the wide applicability of this novel strategy to a series of representative pathogen antigens such as SARS-RBD, MERS-RBD, Mpox-M1, MenB-fHbp, and Tularemia-Tul4 was further confirmed. Charge modification of antigens provides a straightforward approach for antigenicity optimization of alum-adjuvanted vaccines, which has great potential to be adopted as a global defense against infectious diseases.

Association of pain management and positive expectations with psychological distress and spiritual well­being among terminally ill cancer patients admitted to a palliative care unit.

BACKGROUND: Although palliation of psycho-spiritual distress is of great importance in terminally ill cancer patients, there is a little information about screening patients who benefit from palliative care and identifying the cancer care targets. This study explored the relationship of pain management and positive expectations with depression, anxiety and spiritual well-being (SWB) in terminal cancer patients admitted to a palliative care unit. METHODS: Eighty-four terminal cancer inpatients were recruited from the Hospice Ward, Shengjing Hospital of China Medical University. Optimism and general self-efficacy (GSE) were evaluated at admission. Patients completed self-report questionnaires on SWB, depression, anxiety and pain both on admission and one week later. The repeated designed analysis of variance was used to explore the correlates of depression, anxiety and SWB (meaning, peace, faith). RESULTS: In our sample, only cancer pain diminished significantly one week later. For depression (p = 0.041) and faith (p = 0.013), there was a significant pain group (relieved vs. not relieved) × time interaction effect, such that those with satisfied pain control experienced the improved psycho-spiritual outcomes at 1 week. The relationship between positive expectations, peace and faith was also statistically significant, indicating that the improvement of peace or faith was significant in the low group of optimism and GSE. CONCLUSIONS: Our findings indicated that pain management lied at the center of depression and SWB, meaning that effective pain management may reduce depression, and improve SWB among terminal cancer patients. Moreover, positive expectations, especially for optimism, may be the new target for SWB-related intervention research. Palliative care nurse should require the identification of terminal cancer patients who may more benefit from short-term palliative care, and target them with effective cancer care.

What's behind deliberation? The effect of task-related mind-wandering on post-incubation creativity.

Previous studies have already suggested that the deliberate nature of Mind-Wandering (MW) is critical for promoting creative performance. However, the deliberate nature of MW may be mixed up with task-relatedness. Whether the deliberate nature or task-relatedness of MW is responsible for such positive influence remains unclear. The present study tried to address this issue by investigating the influence of deliberate MW (MW-d) and task-related MW (MW-r) on post-incubation creative performance. Our result showed that MW-d is positively correlated with MW-r and spontaneous MW (MW-s) is highly positively correlated with task-unrelated MW (MW-u). Meanwhile, after controlling the possible confounding variables (i.e., the pre-incubation creative performance, the performance during distraction task, and motivation on creative ideation), both MW-d and MW-r predicted participants' AUT performance after incubation. However, the prediction model based on MW-r was stable while the MW-d-based prediction model was not. These findings indicate that the task-relatedness of MW, instead of its deliberate nature, might have a positive influence on subsequent creative performance.

Lung-Targeted Transgene Expression of Nanocomplexed Ad5 Enhances Immune Response in the Presence of Preexisting Immunity.

Recombinant adenovirus serotype 5 (Ad5) vector has been widely applied in vaccine development targeting infectious diseases, such as Ebola virus disease and coronavirus disease 2019 (COVID-19). However, the high prevalence of preexisting anti-vector immunity compromises the immunogenicity of Ad5-based vaccines. Thus, there is a substantial unmet need to minimize preexisting immunity while improving the insert-induced immunity of Ad5 vectors. Herein, we address this need by utilizing biocompatible nanoparticles to modulate Ad5-host interactions. We show that positively charged human serum albumin nanoparticles ((+)HSAnp), which are capable of forming a complex with Ad5, significantly increase the transgene expression of Ad5 in both coxsackievirus-adenovirus receptor-positive and -negative cells. Furthermore, in charge- and dose-dependent manners, Ad5/(+)HSAnp complexes achieve robust (up to 227-fold higher) and long-term (up to 60 days) transgene expression in the lungs of mice following intranasal instillation. Importantly, in the presence of preexisting anti-Ad5 immunity, complexed Ad5-based Ebola and COVID-19 vaccines significantly enhance antigen-specific humoral response and mucosal immunity. These findings suggest that viral aggregation and charge modification could be leveraged to engineer enhanced viral vectors for vaccines and gene therapies.

Boosting Reactive Oxygen Species Generation Using Inter-Facet Edge Rich WO3 Arrays for Photoelectrochemical Conversion.

Water oxidation reaction leaves room to be improved in the development of various solar fuel productions, because of the kinetically sluggish 4-electron transfer process of oxygen evolution reaction. In this work, we realize reactive oxygen species (ROS), H2 O2 and OH⋅, formations by water oxidation with total Faraday efficiencies of more than 90 % by using inter-facet edge (IFE) rich WO3 arrays in an electrolyte containing CO3 2- . Our results demonstrate that the IFE favors the adsorption of CO3 2- while reducing the adsorption energy of OH⋅, as well as suppresses surface hole accumulation by direct 1-electron and indirect 2-electron transfer pathways. Finally, we present selective oxidation of benzyl alcohol by in situ using the formed OH⋅, which delivers a benzaldehyde production rate of ≈768 µmol h-1 with near 100 % selectivity. This work offers a promising approach to tune or control the oxidation reaction in an aqueous solar fuel system towards high efficiency and value-added product.

Addiction-Prone Personality and Creative Cognitive Styles: A Moderated Mediation Model of Novelty Seeking and Depression Tendency.

This study attempted to examine the mechanism of the impact of Addiction-Prone Personality (APP) on creative cognitive styles (idea generation, idea selection), especially to explore the mediating role of novelty seeking and the moderating role of depression tendency on the relationship between APP and creative cognitive styles. College students (N = 576, 79% female) participated in and completed measures of APP, idea generation and selection, novelty seeking, and depression tendency. Results showed that (1) APP was positively related with idea generation while negatively related with idea selection; (2) novelty seeking played a partial mediating role in the relationship between APP and idea generation and a suppressing effect between APP and idea selection; (3) depression tendency moderated the indirect relationship between APP and creative cognitive styles through novelty seeking. Therefore, APP has different indirect effects on idea generation and idea selection via novelty seeking. When there was a higher depression tendency, there was a stronger indirect effect. The study highlights the significant importance of the underlying processes between APP and creative cognitive styles and offers implications for rethinking the relationship between addiction and creativity.

Recent Progress in Doped g-C3N4 Photocatalyst for Solar Water Splitting: A Review.

Graphitic carbon nitride (g-C3N4) photocatalysis for water splitting is harvested as a fascinating way for addressing the global energy crisis. At present, numerous research subjects have been achieved to design and develop g-C3N4 photocatalysis, and the photocatalytic system still suffers from low efficiency that is far from practical applications. Here, there is an inspiring review on the latest progress of the doping strategies to modify g-C3N4 for enhancing the efficiency of photocatalytic water splitting, including non-metal doping, metal doping, and molecular doping. Finally, the review concludes a summary and highlights some perspectives on the challenges and future research of g-C3N4 photocatalysts.

Self-cycled photo-Fenton-like system based on an artificial leaf with a solar-to-H2O2 conversion efficiency of 1.46.

Millions of families around the world remain vulnerable to water scarcity and have no access to drinking water. Advanced oxidation processes (AOPs) are an effective way towards water purification with qualified reactive oxygen species (ROSs) while are impeded by the high-cost and tedious process in either input of consumable reagent, production of ROSs, and the pre-treatment of supporting electrolyte. Herein, we couple solar light-assisted H2O2 production from water and photo-Fenton-like reactions into a self-cyclable system by using an artificial leaf, achieving an unassisted H2O2 production rate of 0.77 µmol/(min·cm2) under 1 Sun AM 1.5 illumination. Furthermore, a large (70 cm2) artificial leaf was used for an unassisted solar-driven bicarbonate-activated hydrogen peroxide (BAP) system with recycled catalysts for real-time wastewater purification with requirements for only water, oxygen and sunlight. This demonstration highlights the feasibility and scalability of photoelectrochemical technology for decentralized environmental governance applications from laboratory benchtops to industry.

Guanylated Hyperbranched Polylysines with High In Vitro and In Vivo Antifungal Activity.

With the rapid growth of fungal infections and the emergence of multi-drug resistant (MDR) fungal strains, new antifungals with novel mechanisms are a pressing need to tackle this emerging health problem. Herein it is reported for the first time that hyperbranched polylysine (HPL) shows antifungal activities against Candida, especially for drug-sensitive and MDR C. albicans strains, and broad-spectrum antibacterial activities against both Gram-negative and Gram-positive bacteria. The high antimicrobial activities are ascribed to the high charge density and compact size of the globular structure of HPL. The in vitro antifungal activities of HPL3 are further enhanced by the modification of amine groups to form guanylated polylysines (HPL3-Gxs). Similar to antimicrobial peptides (AMPs), HPLs and HPL3-Gxs interact with and lyse the membranes of microbes, which mitigates the emergence of drug resistance. HPLs and HPL3-Gxs demonstrate excellent in vivo antimicrobial efficacies against both lethal C. albicans challenge in the invasive candidiasis model and lethal Methicillin resistant Staphylococcus aureus challenge in the peritonitis model, and have potentials as broad-spectrum antimicrobials.

CO2-assisted 'Weathering' of Steel Slag-Derived Calcium Silicate Hydrate: A Generalized Strategy for Recycling Noble Metals and Constructing SiO2-Based Nanocomposites.

The spent adsorbent loaded by toxic metals is a solid hazardous waste which could cause significant secondary pollution due to potential possible additional release of metal ions. Therefore, the main subject is direct reutilization of spent adsorbents which can further economically and realistically offer new features, like recycling metal adsorbed, or formation of functional SiO2-based nanocomposites. The nanoporous structure and negative surface charges enable steel slag-derived amorphous calcium silicate hydrate (CSH) to retain effectively the incoming metal ions (e. g. Au3+, Ag+, Pd2+, Fe3+, Co2+, Ni2+, Cu2+, Zn2+, Ce3+, Y3+, and Gd3+) by chemisorption. Sparked by natural carbonation 'weathering', which ultimately sequestrates atmospheric CO2 by alkaline silicate minerals to leach calcium from mineral matrix, the decalcification reactions of metal-bearing CSH results in successful recovery of noble metals (Ag, Au, Pd) upon NaOH etching the resultant SiO2 support. Further, SiO2-based heterostructures, containing nanocrystalline metals (e. g. Au0, Ag0, Pd0, Fe0, Co0, Ni0, Cu0, and Zn0) or rare-earth oxides (e. g. CeO2, Y2O3, and Gd2O3), are formed after reduction in H2/Ar (5 vol% H2) flow, which is also very important for the multipurpose immobilization of diverse hybrid materials on SiO2 surface (e. g. Cu0-Ag0@SiO2, Cu0-CeO2@SiO2, and Cu0-Ag0-CeO2@SiO2).

The Interactive Model of L2 Listening Processing in Chinese Bilinguals: A Multiple Mediation Analysis.

Second language (L2) listening is a common challenge for language learners. It remains largely unknown how bilinguals process L2 listening. The literature has suggested an interactive model of L2 listening processing. However, few studies have examined the model from an experimental approach. The current study tried to provide empirical evidence for the interactive model of L2 listening processing in bilinguals by exploring the relationships among English spoken word segmentation (SWS), cognitive inhibition, cognitive flexibility, and L2 listening proficiency. The results showed positive associations among SWS, cognitive inhibition, cognitive flexibility, and L2 listening proficiency. Mediation analysis suggested that SWS might have a positive influence on L2 listening proficiency both directly and indirectly through cognitive inhibition and cognitive flexibility, respectively. These results imply that both bottom-up (reflected at SWS) and top-down (reflected at cognitive inhibition and flexibility) processes are engaged in bilinguals' L2 listening processing.