Search Results (3,672)

At present, the energy consumption and carbon emissions of maritime transportation have raised concerns about environmental issues. A potential way to reduce carbon emissions from vessels is the use of chemical-based carbon capture and storage (CCS) technology. However, this technology faces challenges such as high energy consumption, large space occupation, and high processing costs. Therefore, the development of a technology with low energy consumption and compact CO₂ storage is crucial to promote the advancement of CCS technology. This paper introduces a magnesium CO₂ battery system that converts CO₂ into new energy, in the form of hydrogen, while storing CO₂. By preparing highly efficient catalytic electrodes and testing the electrolyte and CO₂ flow rate on the battery performance, the optimal process parameters were determined to be Pd/CeO₂-oct for the electrodes, a 0.5 mol/L NaOH solution for the electrolyte, and a CO₂ flow rate of 1 L/h. The battery system demonstrated high cycling stability and conversion efficiency at a current density of 8 mA·cm⁻², with a stable cycling time of 600 min (20 cycles), a cathode hydrogen production of 10.135 mL, and a Faraday efficiency of 97.03%. Full article

Human dental tissue mesenchymal stem cells (DT-MSCs) constitute an attractive alternative to bone marrow-derived mesenchymal stem cells (BM-MSCs) for potential clinical applications because of their accessibility and anti-inflammatory capacity. We previously demonstrated that DT-MSCs from dental pulp (DP-MSCs), periodontal ligaments (PDL-MSCs), and gingival tissue (G-MSCs) show immunosuppressive effects similar to those of BM, but to date, the DT-MSC-mediated immunoregulation of T lymphocytes through the purinergic pathway remains unknown. In the present study, we compared DP-MSCs, PDL-MSCs, and G-MSCs in terms of CD26, CD39, and CD73 expression; their ability to generate adenosine (ADO) from ATP and AMP; and whether the concentrations of ADO that they generate induce an immunomodulatory effect on T lymphocytes. BM-MSCs were included as the gold standard. Our results show that DT-MSCs present similar characteristics among the different sources analyzed in terms of the properties evaluated; however, interestingly, they express more CD39 than BM-MSCs; therefore, they generate more ADO from ATP. In contrast to those produced by BM-MSCs, the concentrations of ADO produced by DT-MSCs from ATP inhibited the proliferation of CD3⁺ T cells and promoted the generation of CD4⁺CD25⁺FoxP3⁺CD39⁺CD73⁺ Tregs and Th17⁺CD39⁺ lymphocytes. Our data suggest that DT-MSCs utilize the adenosinergic pathway as an immunomodulatory mechanism and that this mechanism is more efficient than that of BM-MSCs. Full article

The electrochemical oxidation of anodic metals (M = nickel and palladium) in an acetonitrile solution of the thiosemicarbazone ligands (E)-2-(1-(4-methoxyphenyl)ethylidene)-N-methylhydrazine-1-carbothioamide (a), (E)-2-(1-(p-tolyl)ethylidene)hydrazine-1-carbothioamide (b), and (E)-N-phenyl-2-(1-(p-tolyl)ethylidene)hydrazine-1-carbothioamide (c) yielded the homoleptic complexes [ML₂], 1a, 1b, 1c, and 2c and [M₄L₄], 2a as air-stable solids. The crystal structures for 1a, 1b, 1c, and 2c show the ligands in a transoid disposition with the [S,S] and [N,N] donor atom pairs occupying cis positions on the nearly square planar coordination plane of the metal. The structure for 2a of S4 symmetry comprises a tetranuclear palladacycle where the metalated ligands are arranged around a central Pd₄S₄ environment: a crown ring with alternating palladium and sulfur atoms. The latter complex is the first example of an electrochemical preparation of a cyclometalated palladium compound, marking a milestone in the chemistry of such species. The compounds have been fully characterized by elemental microanalysis, mass spectrometry, infrared (IR), and ¹H nuclear magnetic resonance (NMR) spectra. Full article

In the last few decades, obesity played a pivotal role by having a high impact on global economic and health systems due to its associated diseases, with cardiovascular, respiratory, musculoskeletal, oncological, mental, and social implications. One of the most incriminated physiopathological mechanisms in obesity is chronic inflammation. The primary goal of this pilot study was to determine the molecular aspects of inflammation among patients with obesity compared to participants with a normal BMI (≤25 kg/m²), as well as within a smaller subset of obese individuals who have been evaluated three months following sleeve gastrectomy. The research employs conventional blood tests and plasma measurements of particular molecules, such as proinflammatory cytokines and proteins that play critical roles in immune and inflammatory regulation. The results revealed a promising kinetic effect after bariatric surgery on IL-18, MCP-1, and PD-L1 molecules. The proinflammatory makers IL-18 (p = 0.006) and MCP-1 (p = 0.035) were elevated in the obese group compared to the control, while the follow-up group displayed lower levels of these molecules. Commonly investigated in oncology related studies, PD-L1 was recently linked to adipose tissue gain and its associated inflammatory effect. Until now, there is no clinical evidence for the relationship between circulating PD-L1 and proinflammatory markers derived from low-grade inflammation of the adipose tissue. The circulating PD-L1 levels were significantly lowered in the obese group compared to the control (p = 0.049), and after sleeve gastrectomy, the PD-L1 level increased. The present study is the first investigating this type of crosstalk and its potential involvement in bariatric patient management. Full article

Wild edible mushrooms are an important food source globally and have a crucial role in forest ecosystems. However, there is limited research on the growth characteristics and the contribution of agronomic traits to biomass, and the environmental factors affecting mushroom growth are limited. This study was conducted in the Qilian Mountains, China, and focused on investigating the growth patterns and agronomic traits of Lyophyllum decastes and Coprinus comatus. The results revealed that the growth of these mushrooms followed a logical growth curve. By calculating the model parameters, we obtained the maximum daily growth of height (PH), pileus diameter (PD), and cluster perimeter (CP) of L. decastes on the 5th, 7th, and 7th days, respectively, with values of 0.55 cm d⁻¹, 0.54 cm d⁻¹, and 4.54 cm d⁻¹, respectively. However, the maximum daily growth of PH, pileus length (PL), and PD of the C. comatus appeared on the 3rd day, 2nd day, and 2nd day of the observation, respectively. This study identified near-surface relative humidity, air relative humidity, and rainfall as the primary factors influencing mushroom growth, as indicated by Pearson’s correlation analysis, redundancy analysis (RDA), and multiple linear and stepwise regression. Additionally, land surface temperature and air temperature were also identified as important factors affecting mushroom growth. By utilizing random forest and stepwise regression analysis, this study identified PH and stipe diameter (SD) as the most crucial agronomic traits affecting mushroom biomass. Overall, this study offers insights for industrial mushroom cultivation and basic fungal research. Full article

Programmed cell death 1 (PD-1) and programmed death-ligand 1 (PD-L1) interact to form an immune checkpoint fostering viral infection and viral oncogene-induced tumorigenesis. We generated a novel anti-human PD-1, humanized monoclonal antibody P1801 and investigated its pharmacologic, pharmacokinetic (PK), and pharmacodynamic properties. In vitro binding assays revealed that P1801 uniquely binds to human PD-1 and inhibits its interaction with PD-L1/2. It showed a minor effect on the induction of antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). P1801 significantly induced the release of IL-2 from activated T-cells but not from nonactivated T-cells. A dose-dependent linear PK profile was observed for the cynomolgus monkeys treated with repeated doses of P1801 at 5 mg/kg to 200 mg/kg once weekly. A four-week repeat-dose toxicity study revealed that P1801 given weekly was safe and well tolerated at doses ranging from 5 to 200 mg/kg/dose. No pathological abnormalities were noted. In humanized PD-1 mice harboring human PD-L1-expressing colon tumor cells, P1801 administered intraperitoneally twice per week at 12 mg/kg significantly inhibited tumor growth and prolonged mouse survival. P1801 displayed unique binding properties different from pembrolizumab and nivolumab. Therefore, it showed distinctive immunological reactions and significant antitumor activities. We are initiating a Phase 1 clinical study to test its combination use with ropeginterferon alfa-2b, which also has antiviral and antitumor activities, for the treatment of cancer. Full article

(1) Background: This study investigates the tumor immune microenvironment, focusing on immune cell distribution in lung adenocarcinoma. (2) Methods: We evaluated fifty cases of lung adenocarcinoma, and suitable areas for further studies were annotated on the histological slides. Two tumor cores per case were obtained, one from the tumor’s center and another from its periphery, and introduced into three paraffin receptor blocks for optimized processing efficiency. The 4-micrometer-thick tissue microarray sections were stained for H&E and for CD68, CD163, CD8, CD4, and PD-L1; (3) Results: Our investigation revealed significant correlations between PD-L1 expression in tumor cells and the presence of CD163+ macrophages, between CD4+ cells and CD8+, CD68+, and CD163+ cells, and also between CD8+ T cells and CD163+ cells. Additionally, while we observed some differences in cellular components and densities between the tumor center and periphery, these differences were not statistically significant. However, distinct correlations between PD-L1 and immune cells in these regions were identified, suggesting spatial heterogeneity in the immune landscape. (4) Conclusions: These results emphasize the intricate interactions between immune cells and tumor cells in lung adenocarcinoma. Understanding patient spatial immune profile could improve patient selection for immunotherapy, ensuring that those most likely to benefit are identified. Full article

Therapeutic options for pituitary neuroendocrine tumours (PitNETs) refractory to temozolomide are scarce. Immune checkpoint inhibitors (ICIs), particularly inhibitors of the programmed cell death-1 (PD-1) pathway and its ligand (PD-L1), have been experimentally used in aggressive or metastatic PitNETs. We aimed to study the therapeutic usefulness of anti-PD-1 drugs in patients with aggressive or metastatic PitNETs. Published cases and case series involving patients with PitNETs treated with PD-1/PD-L1 inhibitors were reviewed. Demographic data, clinical–pathological features, previous therapies, drug dosage and posology, and the best radiological and biochemical responses, as well as survival data, were evaluated. We identified 29 cases of aggressive (n = 13) or metastatic (n = 16) PitNETs treated with PD-1/PD-L1 inhibitors. The hypersecretion of adrenocorticotropic hormone (ACTH) was documented in eighteen cases (62.1%), seven were prolactinomas (24.1%), and four were non-functioning PitNETs. All patients underwent various therapies prior to using ICIs. Overall, a positive radiological response (i.e., partial/complete radiological response and stable disease) was observed in eighteen of twenty-nine cases (62.1%), of which ten and four were ACTH- and prolactin-secreting PitNETs, respectively. Hormonal levels reduced or stabilised after using ICIs in 11 of the 17 functioning PitNET cases with available data (64.7%). The median survival of patients treated with ICIs was 13 months, with a maximum of 42 months in two ACTH-secreting tumours. Among 29 patients with PitNETs treated with PD-1/PD-L1 inhibitors, the positive radiological and biochemical response rates were 62.1% and 64.7%, respectively. Altogether, these data suggest a promising role of ICIs in patients with aggressive or metastatic PitNETs refractory to other treatment modalities. Full article

The fatty acid receptor CD36 is expressed on various malignant cells and is suggested to contribute to tumor progression. CD36 is also expressed by several immune cells and involved in immune responses and may be a potential target in cancer immunotherapy. In this study, we investigated whether the selective inhibition of CD36 can inhibit tumor progression and facilitate an antitumor immune response in oral squamous carcinoma cells (OSCCs). We assessed the effects of sulfosuccinimidyl oleate sodium (SSO), a CD36 inhibitor, on the proliferation apoptosis and alteration in tumor cell surface expression levels of immune accessory molecules in vitro. We also assessed whether SSO-treated OSCCs could promote a T cell response via a Mixed Lymphocyte Reaction (MLR) assay. We also investigated the direct antitumor effects and immunomodulatory effects of SSO using a mouse oral cancer OSCC model. SSO treatment significantly inhibited OSCC proliferation, increased apoptotic cell death, and upregulated the cell surface expression of several immune accessory molecules, including CD83, MHC-Class II, and PD-L1. SSO-treated OSCCs augmented T cell proliferation following MLR. In vivo SSO administration significantly attenuated mouse tumor growth with an increased proportion of immune cells, including CD4⁺ T, CD8⁺ T, and dendritic cells; it also decreased the proportion of immune suppressive cells, such as myeloid-derived suppressor and regulatory T cells. These results suggest that the selective inhibition of CD36 can induce direct and indirect antitumor effects by facilitating host antitumor immune responses in OSCCs. Full article

Background: Ovarian mesonephric-like adenocarcinoma (MLA) is a newly described histological type known for its aggressive behavior. This study aims to determine the frequency of ovarian MLA, review the existing literature, and elucidate its clinicopathological characteristics, including the potential therapeutic targets. Methods: We retrospectively reviewed the pathological diagnoses of 501 primary ovarian cancer surgical cases at our institution from 2010 to 2023. MLAs exhibiting typical morphological and immunohistochemical features were included. The frequency and clinicopathological characteristics of these cases were summarized. Additionally, we conducted a literature search using PubMed to collect and summarize previously reported cases of ovarian MLAs. Results: Among the 501 primary ovarian cancer cases, we identified 3 cases (0.6%) of MLA. The patients were 52–76 years old, and the initial FIGO stages were IC1 (two cases) and IIIB (one case). All the cases exhibited HRP, pMMR, PD-L1 negativity (CPS < 1), and low HER2 expression. Two cases experienced metastatic recurrence. A literature review identified 97 cases of MLA. The MLAs frequently exhibited KRAS mutations (90%, 38/42), with a recurrence rate of 39% (26/67). Conclusion: MLAs accounted for 0.6% of malignant ovarian tumors at our institution, all of which were advanced or recurrent cases. These cases showed HRP, pMMR, and PD-L1 negativity, indicating a lack of current therapeutic targets. The literature also reported a high incidence of advanced and recurrent cases, highlighting the need for accurate diagnosis and the development of new treatments. The frequent KRAS mutations suggest a potential therapeutic target for recurrent or metastatic MLA. Full article

In patients with metastatic estrogen-receptor (ER)-positive HER2-negative breast cancer, the loss of ER expression and the mutation of ESR1—the gene encoding the ER receptor—are mechanisms for resistance to endocrine therapy. We aimed to determine the frequency of these mechanisms and their interaction. Metastases were retrieved from our pathology files. ESR1 hotspot mutations resulting in p.(D538G), p.(Y537S), and p.(L536H) were determined by means of pyrosequencing. Clinical data were retrieved from electronic medical records. A total of 136 metastases were available for analysis. ER loss was found in 23 metastases (17%). ESR1 mutations were found in 18 metastases (13%), including p.(D538G) in 9, p.(Y537S) in 7, and p.(L536H) in 2. ESR1 mutation and ER loss were mutually exclusive (p = 0.042), and ESR1 mutation was associated with endocrine therapy (p = 0.002). ESR1 mutation was found in two primary breast cancers. ESR1 mutations are rare in primary breast cancer and develop in metastases during endocrine therapy. Furthermore, ER loss had a statistically significant negative effect on overall survival when compared to patients without ER loss, with a rate ratio of 3.21 (confidence interval 1.95–5.26). No such effect was observed for ESR1 mutations, with a rate ratio of 1.15 (confidence interval 0.67–1.95). We conclude that ER loss and ESR1 mutation together account for 30% of the resistance to endocrine therapy. Full article

This study aimed to identify hub genes involved in regulatory T cell (Treg) function and migration, offering insights into potential therapeutic targets for cancer immunotherapy. We performed a comprehensive bioinformatics analysis using three gene expression microarray datasets from the GEO database. Differentially expressed genes (DEGs) were identified to pathway enrichment analysis to explore their functional roles and potential pathways. A protein-protein interaction network was constructed to identify hub genes critical for Treg activity. We further evaluated the co-expression of these hub genes with immune checkpoint proteins (PD-1, PD-L1, CTLA4) and assessed their prognostic significance. Through this comprehensive analysis, we identified CCR8 as a key player in Treg migration and explored its potential synergistic effects with ICIs. Our findings suggest that CCR8-targeted therapies could enhance cancer immunotherapy outcomes, with breast invasive carcinoma (BRCA) emerging as a promising indication for combination therapy. This study highlights the potential of CCR8 as a biomarker and therapeutic target, contributing to the development of targeted cancer treatment strategies. Full article

PAK4 and PD-L1 have been suggested as novel therapeutic targets in human cancers. Moreover, PAK4 has been suggested to be a molecule closely related to the immune evasion of cancers. Therefore, this study evaluated the roles of PAK4 and PD-L1 in the progression of osteosarcomas in 32 osteosarcomas and osteosarcoma cells. In human osteosarcomas, immunohistochemical positivity for the expression of PAK4 (overall survival, p = 0.028) and PD-L1 (relapse-free survival, p = 0.002) were independent indicators for the survival of patients in a multivariate analysis. In osteosarcoma cells, the overexpression of PAK4 increased proliferation and invasiveness, while the knockdown of PAK4 suppressed proliferation and invasiveness. The expression of PAK4 was associated with the expression of the molecules related to cell cycle regulation, invasion, and apoptosis. PAK4 was involved in resistance to apoptosis under a treatment regime with doxorubicin for osteosarcoma. In U2OS cells, PAK4 was involved in the stabilization of PD-L1 from ubiquitin-mediated proteasomal degradation and the in vivo infiltration of immune cells such as regulatory T cells and PD1-, CD4-, and CD8-positive cells in mice tumors. In conclusion, this study suggests that PAK4 is involved in the progression of osteosarcoma by promoting proliferation, invasion, and resistance to doxorubicin and stabilized PD-L1 from proteasomal degradation. Full article

Aims: This study was conducted to systematically evaluate the biomechanical impact of varying degrees of root and bone resorption resulting from periodontitis and orthodontic tooth movement (OTM) on the mandibular anterior teeth. The objective was to determine whether these distinct resorption patterns exert a specific influence on tooth displacement and strain patterns. Methods: A finite element (FE) model of an idealized anterior mandible from the first premolar in the third to the fourth quadrant was developed without bone or root resorption and a constant periodontal ligament (PDL) thickness of 0.2 mm. Variations included three root resorption levels (0%, 20%, 50%) and three bone resorption types (circular 50%, circular 80%, vestibular 80%). Models ranged from 200,000 to 440,000 elements and 55,000 to 130,000 nodes. Orthodontic forces, namely root torque (5 Nmm), intrusion (0.2 N), and distalization (0.5 N) were applied for subsequent crown displacement and PDL strain analysis. Results: A total of 180 simulations were performed. Simulations showed that displacement was similar across different bone resorption conditions, irrespective of modeled root resorptions. Circumferential bone resorption increased tooth displacement, regardless of root resorption status. Vestibular bone resorption exhibited less increase in tooth displacement. However, when accompanied by root resorption, the combination exacerbated tooth displacement. Strains in the PDL clearly increased with a circumferential bone resorption of 80%. Conclusions: This study highlights the critical role of bone resorption in tooth displacement during OTM, particularly the challenges associated with circumferential resorption. Clinicians must consider both bone and root resorption for personalized medicine treatment of patients with severe periodontitis, in favor of low-force application strategies to optimize outcomes and minimize complications linked to excessive tooth displacement. Full article

Background: The aim of the study was to investigate a series of complete blood cell count-based biomarkers of systemic inflammation as predictors of clinical outcomes in patients who underwent first-line chemoimmunotherapy for advanced NSCLC. Methods: Consecutive patients with pathologically diagnosed stage III/IV NSCLC and PD-L1 < 50% who underwent first-line chemoimmunotherapy were retrospectively enrolled. The clinical outcomes used for biomarker evaluation were Objective Response Rate (ORR) and Overall Survival (OS). Results: Non-responders had significantly higher values of neutrophil to lymphocyte ratio (NLR, median: 5.36; IQR: 2.78–10.82 vs. 3.31; IQR: 2.15–4.12, p = 0.019), neutrophil to monocyte ratio (NMR, median: 14.00; IQR: 8.82–21.20 vs. 9.20; IQR: 7.45–11.20, p = 0.013), and systemic inflammation index (SII, median: 1395; IQR: 929–3334 vs. 945; IQR: 552–1373, p = 0.025), but only NLR and NMR remained independently associated with clinical response in multivariate logistic regression. In the univariate analysis, white blood cells (OR:1.2202; 95% CI: 1.0339–1.4400, p = 0.019), neutrophils (OR:1.2916; 95% CI: 1.0692–1.5604, p = 0.008), NLR (OR:1.3601: 95% CI: 1.0949–1.6896, p = 0.005) and NMR (OR:1.2159; 95% CI: 1.00396–1.4221, p = 0.015) were significantly associated with survival; Cox regression models confirmed that neutrophils, NLR, and MLR were independently associated with survival; NLR, at a cut-off value of 4.0, showed the better AUC (0.749) in predicting OS. Conclusions: Baseline complete blood cell count biomarkers, especially the NLR, can predict clinical outcomes in patients with advanced NSCLC treated with first-line chemoimmunotherapy. Full article