Search Results (2,364)

Background/Objectives: Objective memory decline is associated with poor quality of life (QOL) in Parkinson’s disease (PD, but it is unclear what role perception of memory (metamemory) plays. The Multifactorial Memory Questionnaire (MMQ) measures metamemory and is proposed to have a three-factor structure, but the factor structure of the MMQ in PD has not been explored. The current study examined (i) the factor structure of the MMQ in PD and (ii) the relationship between the metamemory and QOL in PD. Methods: This longitudinal, observational study involved 149 participants with PD (98 males, M age = 65.78 years, SD = 9.25). Participants completed the MMQ and the Unified Parkinson’s Disease Rating Scale (disease severity) at baseline, and the Parkinson’s Disease Questionnaire-39 (QOL) two years later. Results: Confirmatory factor analysis revealed both the three-factor and four-factor models were inadequate. Exploratory factor analysis resulted in a four-factor solution. The contentment and ability subscales from the original factor structure remained, while the strategies subscale was divided into external strategies and internal strategies. Disease severity, ability, and internal strategies uniquely predicted QOL. Individuals who reported low subjective memory ability and high use of internal strategies reported worse QOL two years later. Conclusions: These findings indicate that metamemory predicts QOL in PD and suggest that improved perceived memory ability and strategy use could offer avenues for improved QOL. Full article

In this study, nonsingular modeling and cross-domain trajectory tracking control problems for a special class of coaxial hybrid aerial–underwater vehicles (HAUVs) are investigated. Coaxial HAUVs need to effectively overcome the influence of hydrodynamic factors when moving underwater, so the attitude angle required by coaxial HAUVs is much larger than that in the air. The attitude representation based on quaternion modeling is adopted to avoid the inherent singularity of Euler angle modeling. A cascade sliding mode control and proportion differentiation (SMC-PD) controller is proposed, which is used to position trajectory and attitude quaternion tracking control, respectively. An adaptive sliding mode controller based on disturbance observer (DO) enhancement is adopted in the outer loop to carry trajectory tracking control. At the same time, the expected attitude angle is calculated by the outer loop (position) and is converted into the expected quaternion. With reference to the idea of enhanced robustness in active disturbance rejection control (ADRC), a feedforward proportion derivation (PD) controller based on DO enhancement is used to track the desired quaternion. A variable parameter adaptive algorithm based on the learning rate is introduced in the cascaded SMC-PD controller. The error convergence speed of the system is further improved by adaptively changing the controller parameters. The stability of the proposed control scheme is proved by using the Lyapunov theory. The numerical simulation results show that the controller has good robustness and effectiveness. Full article

Background/Objectives: A significant breakthrough in non-small-cell lung cancer (NSCLC) treatment has occurred with the introduction of targeted therapies and immunotherapy. However, not all patients treated with these therapies would respond to treatment, and patients who respond to treatment would acquire resistance at some time point. This is why we need new biomarkers that can predict response to therapy. The aim of this study was to investigate whether soluble programmed cell death-ligand 1 (sPD-L1) could be a predictive biomarker in patients with epidermal growth factor receptor (EGFR)-positive NSCLC. Materials and Methods: Blood samples from 35 patients with EGFR-mutated (EGFRmut) adenocarcinoma who achieved disease control with EGFR tyrosine kinase inhibitor (EGFR TKI) therapy were collected for sPD-L1 analysis. We analyzed sPD-L1 concentrations in 30 healthy middle-aged subjects, as a control population, to determine the reference range. Adenocarcinoma patients were divided into two groups, i.e., a group with low sPD-L1 (≤182.5 ng/L) and a group with high sPD-L1 (>182.5 ng/L). Results: We found that progression-free survival (PFS) was 18 months, 95% CI (11.1–24.9), for patients with low sPD-L1 and 25 months, 95% CI (8.3–41.7), for patients with high sPD-L1. There was no statistically significant difference in PFS between the groups (p = 0.100). Overall survival (OS) was 34.4 months, 95% CI (26.6–42.2), for patients with low sPD-L1 and 84.1 months, 95% CI (50.6–117.6), for patients with high sPD-L1; there was also no statistically significant difference between the groups (p = 0.114). Conclusion: In our study, we found that patients with high sPD-L1 had numerically better PFS and OS, but this has no statistical significance. Further studies with a larger number of patients are needed to evaluate the role of sPD-L1 as a predictive biomarker in patients with EGFRmut NSCLC. Full article

Arsenic (As) is a risk factor for non-melanoma skin cancer (NMSC). From a six-year follow-up study on 7000 adults exposed to As, we reported the associations of single-nucleotide variation in tumor tissue and gene expression. Here, we identify the associations of small deletions (DELs) and transcriptomic profiles in NMSC. Comparing the (a) NMSC tissue (n = 32) and corresponding blood samples from each patient, and (b) an independent set of non-lesional, healthy skin (n = 16) and paired blood, we identified NMSC-associated DELs. Differential expressions of certain gene pathways (TGF-β signaling pathway, IL-17 pathway, PD-L1 pathway, etc.) showed significant interactions with these somatic DELs and As exposure. In low-As-exposure cases, the DELs in APC were associated with the up-regulation of inflamed T-Cell-associated genes by a fold change (FC) of 8.9 (95% CI 4.5–17.6), compared to 5.7 (95% CI 2.9–10.8) without APC DELs; in high-As-exposure cases, the APC DELs were associated with an FC of 5.8 (95% CI 3.5–9.8) compared to 1.2 (95% CI −1.3 to 1.8) without APC DELs. We report, for the first time, the significant associations of somatic DELs (many in STR regions) in NMSC tissue and As exposure with many dysregulated gene pathways. These findings may help in selecting groups of patients for potential targeted therapy like PD-L1 inhibitors, IL-17 inhibitors, and TGF-β inhibitors in the future. Full article

The ability to recognize hidden symmetry in a highly asymmetric world is a key factor in how we view and understand the world around us. Despite the fact that it is an intrinsic property of the natural world, we have an innate ability to find hidden symmetry in asymmetric objects. The inherent asymmetry of the natural world is a fundamental property built into its chemical building blocks (e.g., proteins, carbohydrates, etc.). This review highlights the role of asymmetry in the structure of the carbohydrates and how these stereochemical complexities present synthetic challenges. This survey starts with an overview of the role synthetic chemistry plays in the discovery of carbohydrates and their 3D structure. This review then introduces various de novo asymmetric synthetic approaches that have been developed for the synthesis of carbohydrates and, in particular, oligosaccharides. The two most successful strategies for oligosaccharide synthesis rely on diastereoselective palladium-catalyzed glycosylation. The first uses an Achmatowicz reaction to asymmetrically prepare pyranose building blocks along with a substrate-controlled Pd-glycosylation. The other strategy couples a ligand-controlled Pd-glycosylation with a ring-closing metathesis for oligosaccharide assembly. Full article

Background: Inflammation is reportedly related to Parkinson’s disease (PD). However, the relationship between the systemic immune-inflammation index (SII) and PD remains unexplored. This study aimed to explore the potential relationship between the SII and PD. Methods: This retrospective cross-sectional study analyzed data from the National Health and Nutrition Examination Survey (NHANES) covering the years 2003 to 2020. We analyzed patients over 40 years of age after excluding those with missing SII, PD and covariate data. Logistic regression, subgroup analysis, and restricted cubic spline models were subsequently conducted to evaluate the associations between the SII and PD. Results: Finally, 30,638 participants were included in this study, of whom 416 (1.36%) were identified as having PD. Weighted multivariate regression analysis, adjusted for all covariates, revealed that participants with elevated in-transform (SII) values had a higher likelihood of PD [OR 1.39; 95% CI (1.02, 1.91), p = 0.039] compared to those with lower SII values. The fully adjusted restricted cubic spline curve revealed that the SII/100 was positively and linearly associated with the incidence of PD (p for nonlinearity > 0.05). Additionally, subgroup analysis revealed a stronger correlation between the SII and PD in female participants [OR = 1.06, 95% CI (1.03, 1.08)] compared to male participants [OR = 1.02, 95% CI (1.00, 1.03)] (p for interaction = 0.01). Conclusions: The SII showed a positive correlation with the incidence of PD, particularly in females. Further large-scale prospective studies are necessary to confirm these findings and explore the causal factors that may contribute to the early prevention of PD. Full article

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC), expecting to be the second leading cause of cancer deaths by 2030, resists immune checkpoint therapies due to its immunosuppressive tumor microenvironment (TME). Leukemia inhibitory factor (LIF) is a key target in PDAC, promoting stemness, epithelial–mesenchymal transition (EMT), and therapy resistance. Phase 1 clinical trials showed anti-LIF therapy is safe but with limited efficacy, suggesting better outcomes when combined with chemotherapy, radiotherapy, or immunotherapy. Methods: We assessed the combination of chemotherapy (gemcitabine/nab-paclitaxel) and dual blockade of LIF and PD-L1 on tumor growth and survival in orthotopic and spontaneous PDAC models. Flow cytometry and scRNA-seq were utilized to monitor the antitumor immune response. The role of key immune cells was further confirmed by depleting these immune cells, including CD4, CD8, or inflammatory monocytes. Results: Sequential treatment with chemotherapy (gemcitabine/nab-paclitaxel) and dual blockade of LIF and PD-L1 significantly improved antitumor efficacy compared to monotherapy or dual combinations of these therapies. This chemo/anti-LIF/anti-PD-L1 approach reduced EMT in tumor cells and enhanced the antitumor immune response, primarily through CD8 T cells, as depleting CD8 cells largely abrogated the effect of treatment. This combination therapy also shifted macrophages and dendritic cells towards an antitumor phenotype. Conclusions: The combination of chemotherapy, anti-LIF, and anti-PD-L1 not only targeted tumor cells but also augmented the anti-tumor immune response. These findings strongly support advancing chemo/anti-LIF/anti-PD-L1 combination therapy to clinical trials in PDAC. Full article

Background/Objectives: Owing to the growing use of immune checkpoint inhibitors (ICIs) in the treatment of cancer, a wide spectrum of toxicity has arisen among cancer patients. Yet, limited ICI toxicity-related research is currently conducted in our region. Methods: This is a retrospective observational study conducted on adult cancer patients who received at least one cycle of ICI single therapy. Toxicity profiles of different ICI monotherapies were described and compared, and their association with different risk factors was assessed. SPSS version 28 was used for statistical analyses, and p < 0.05 was considered statistically significant. Results: A total of 428 patients were treated with anti-PD1 (nivolumab [n = 221, 51.6%] and pembrolizumab [n = 126, 29.5%]) or anti-PD-L1 (atezolizumab [n = 78, 18.2%] and durvalumab [n = 3, 0.7%]). Pneumonia was the most common complication (10%), followed by acute kidney injury (AKI; 8.2%) and hepatitis (7.9%). The proportion of hepatitis cases was significantly higher among atezolizumab compared to nivolumab-, pembrolizumab-, and durvalumab-treated patients (17.95% vs. 7.7% vs. 2.4% vs. 0.0%, respectively; p < 0.001). Gastrointestinal complication (colitis) was detected in 3.3% of patients with a significant difference between treatment groups (4.5%, 1.6%, 1.3%, and 33.3% in nivolumab, pembrolizumab, atezolizumab, and durvalumab, respectively; p = 0.008). Cardiac complications occurred in 1.2% of patients with a significant difference between treatment groups (0.5% in the nivolumab, 3.8% in the atezolizumab, 33.3% in the durvalumab, and none in the pembrolizumab groups (p < 0.001)). Musculoskeletal side effects, including both arthralgia and fatigue, were the most-reported side effects by 39.5% of patients, with significantly higher arthralgia complainers only in nivolumab (7.7%) compared to other treatment groups (0%, 2.6%, and 0% in pembrolizumab, atezolizumab, and durvalumab, respectively, p = 0.007). Hepatic, cardiovascular, hematological, respiratory, renal, gastrointestinal complications, thyroid complications, and dermatological side effects were found to occur on weeks 6, 7.5, 8, 8, 10, 10, 10.5, and 12 after treatment initiation, respectively, with no significant difference between treatment groups. Despite that, hepatitis and AKI tended to occur earlier with atezolizumab (week 2, p = 0.084) and pembrolizumab (week 2, p = 0.062), respectively, compared to their comparators. The female gender and a history of hepatitis were found to increase the odds of hepatic complication with anti-PD1 or anti-PD-L1 use [OR = 2.71; 95% CI 1.07–6.85, OR = 11.14; 95% CI 3.46–35.88, respectively]. Previous exposure to cancer therapy only was found to increase the odds of developing pneumonia among the treated patients [OR = 3.08; 95% CI 1.12–8.85]. Having hematological malignancy influenced the odds of hematological complications positively (either neutropenia or thrombocytopenia) compared to solid malignancies when patients were treated with anti-PD1 or anti-PD-L1 [OR = 17.18; 95% CI 4.06–72.71]. Finally, the female gender was found to positively associate with the odds of nausea/vomiting and fatigue secondary to anti-PD1 or anti-PD-L1 administration [OR = 2.08; 95% CI 1.34–3.21, OR = 1.65; 95% CI 1.09–2.51, respectively]. On the other hand, previous exposure to cancer therapy was found to reduce the risk of having arthralgia with anti-PD1 or anti-PD-L1 administration [OR = 0.344; 95% CI 0.121–0.974]. Conclusions: Treatment with anti-PD1 or anti-PD-L1 was associated with a spectrum of complications and side effects. Several risk factors have been identified to impact their occurrence. ICI toxicities and risk factors influencing their odds should be recognized and considered in clinical practice, as this could help in individualizing therapeutics regimens and avoiding treatment interruption. Full article

This study examines the factors influencing the formation and structure of ZnPd-ZnO active sites supported on TiO₂ by comparing their genesis from Pd/TiO₂ base catalysts prepared by impregnation using different Pd precursors (Pd(NH₃)₄(NO₃)₂ and Pd(acac)₂). The experimental results demonstrated that, in contrast to the production of CO over Pd/TiO₂ base catalysts, the selectivity of methanol over ZnPd-ZnO/TiO₂ catalysts was significantly affected by the dispersion of ZnPd intermetallic particles and the development of ZnPd-ZnO interfaces. These are determined by the characteristics of Pd particles supported on TiO₂ and their contact with the ZnO particles deposited on them. The Pd/TiO₂ base catalyst prepared by impregnation with neutral Pd precursor (Pd(acac)₂) produces a higher concentration and more effective dispersion of the ZnPd intermetallic phase as well as a wider ZnO-ZnPd interface region in comparison to the Pd/TiO₂ counterpart synthetized using the cationic Pd precursor (Pd(NH₃)₄(NO₃)₂). These differences in the ZnPd-ZnO active sites resulted in notable variations in the methanol yield, achieving the catalysts prepared with the neutral precursor about twice higher methanol selectivity from CO₂ hydrogenation at low temperatures. Full article

1,2-Propanediol, with its highly functionalized molecular structure and abundant availability, serves as a viable feedstock for high-value chemicals. The oxidation of 1,2-propanediol can potentially yield lactic acid, an important commodity chemical. Herein, we report the catalytic oxidation of 1,2-propanediol in the presence of NaOH, using Pd nanoparticles (NPs) supported on various functionalized multi-walled carbon nanotubes (MWCNTs). Both single-factor experiments and the response surface methodology were employed to investigate the optimal operating parameters. It was found that nitrogen doping promotes strong metal–support interactions between the active components and the support. Under optimal reaction conditions (123 °C, 1.25 MPa O₂ pressure, 4 h, and a NaOH/1,2-PDO molar ratio of 4.0), a high lactic acid yield of 68.3% was achieved using nitrogen-doped MWCNT-supported Pd nanoparticles as the catalyst. The selectivity for lactic acid decreased with increasing reaction time, temperature, NaOH/1,2-PDO molar ratio, and O₂ pressure, while the conversion rate increased correspondingly. After five cycles, the conversion of 1,2-PDO slightly decreased to 76.2%, while the LA selectivity remained high at 84.9%. Additionally, the reaction pathway was further investigated, confirming the formation mechanism of lactic acid. Full article

This review explores the emerging relationship between obstructive sleep apnea (OSA) and periodontal disease (PD), emphasizing shared inflammatory pathways, overlapping risk factors, and potential systemic health implications. Both conditions are characterized by chronic inflammation and oxidative stress, which independently contribute to cardiovascular disease, diabetes, and other systemic disorders. Evidence suggests a bidirectional relationship, with OSA-related hypoxia exacerbating periodontal tissue breakdown and PD-induced inflammation potentially influencing OSA severity. However, the causative nature of the relationship between OSA and PD remains uncertain, largely due to inconsistencies in diagnostic criteria, methodological variability, and study heterogeneity. This review highlights the essential role of systematic reviews (SRs) in synthesizing current evidence, identifying research gaps, and guiding future studies. To maximize their impact, SRs should adhere to rigorous methodological quality standards, improve transparency in data reporting, and address the heterogeneity of included studies. Future research should focus on longitudinal and interventional designs, standardize diagnostic protocols, and investigate biomarkers, oral microbiome profiles, and inflammatory mediators to elucidate the mechanisms linking OSA and PD. Multidisciplinary collaboration between dental and sleep specialists is crucial to advancing evidence-based strategies that improve patient outcomes and address the broader health implications of these often coexisting conditions. Full article

The human body contains ~10¹⁴ cells—each of which is separated by a lipid bilayer, along with its organeller. Unsaturated fatty acids are located on the external layer and, as a result, are particularly exposed to harmful factors, including xenobiotics and ionising radiation. During this activity, lipid peroxidation products are generated, e.g., 4-hydroxy-2-nonenal (HNA), 4-oxo-2(E)-nonenal (ONE), and malondialdehyde (MDA). The mentioned aldehydes can react with cytosolic 2′-deoxynucleosides via Michael addition. In this paper, the following adducts have been taken into theoretical consideration: ε-dCyt, H-ε-dAde, ε-dCyt, H-ε-dAde, H-ε-dGua, R/S-OH-PdGua, N2,3-ε-dGua, M1-dGua, N1-ε-dGua, and HNE-dGua. The presence of the above molecules can alter a cell’s antioxidant pool. With this in mind, the adiabatic ionisation potential (AIP) and vertical ionisation potential (VIP), as well as the spin and charge distributions, are discussed. For this purpose, DFT studies were performed at the M06-2x/6-31++G** level of theory in the aqueous phase (both non-equilibrated (NE) and equilibrated (EQ) solvent–solute interaction modes), together with a Hirshfeld charge and spin distribution analysis. The obtained results indicate that the AIPs of all the investigated molecules fell within a range of 5.72 and 5.98 eV, which is consistent with the reference value of 7,8-dihydro-8-oxo-2′-deoxyguanosine (^OXOdGua), 5.78 eV. N2,3-ε-dGua and M1-dGua were the only exceptions, whose VIP and AIP were noted as higher. The electronic properties analysis of 2′-deoxynucleoside adducts with lipid peroxidation products reveals their potential influence on the cells’ antioxidant pool, whereby they can affect the communication process between proteins, lipids, and nucleotides. Full article

The size of viral genomes is limited, thus the majority of encoded proteins possess multiple functions. The main function of tobamoviral movement protein (MP) is to perform plasmodesmata gating and mediate intercellular transport of the viral RNA. MP is a remarkable example of a protein that, in addition to the initially discovered and most obvious function, carries out numerous activities that are important both for the manifestation of its key function and for successful and productive infection in general. Briefly, MP binds the viral genome, delivers it to the plasmodesmata (PD) and mediates its intercellular transfer. To implement the transport function, MP interacts with diverse cellular factors. Each of these cellular proteins has its own function, which could be different under normal conditions and upon viral infection. Here, we summarize the data available at present on the plethora of cellular factors that were identified as tobamoviral MP partners and analyze the role of these interactions in infection development. Full article

Background: Anti-PD-1-based immunotherapy has improved outcomes in stage IIB to IV resected melanoma patients in clinical trials. However, little is known about real-world outcomes, prognostic factors and patterns of relapse. Methods: This is a retrospective multicenter observational study including patients with resected melanoma treated with subsequent anti-PD-1-based adjuvant immunotherapy. Data on clinical and demographic characteristics, delivered treatment, prognostic factors, time and pattern of relapse were collected. Results: We included 245 patients from eight centers; 4% of patients were at stage IIB-C, 80% at stage IIIA-D and 16% at stage IV. Recurrence-free survival (RFS) rates at 18 and 36 months were 60% and 48%, respectively, with a median RFS of 33.7 months. Prognostic factors associated with recurrence were melanoma primary site (HR 2.64, 95% CI 1.15–6.01) and starting adjuvant therapy more than 12 weeks after the last resection (HR 1.68, 95% CI 1.13–2.5); presence of serious immune-related adverse events was associated with better RFS (HR 0.4, 95% CI 0.19–0.87). Early relapses accounted for 63% of the total recurrences, with a higher number of metastatic sites (18%); in contrast, late relapses presented more frequently with brain metastases (20%). Conclusions: In our patients with resected melanoma who underwent anti-PD-1-based adjuvant immunotherapy, survival outcomes were worse than those reported in clinical trials. Primary melanoma site and time interval between the last resection and the start of adjuvant therapy were associated with survival. Full article

Water and land resources (WLR) are the most important basic resources for social and economic development. The effective alignment of WLR is crucial for maximizing resource utilization and promoting sustainable regional development. This study focuses on Western Jilin Province (WJP), China, employing the degree of coupling coordination model, spatial autocorrelation, and the center of gravity transfer model to assess and characterize the spatio-temporal differentiation patterns of water and land resource matching from 2006 to 2020. Five indicators—annual average temperature (AAT), urbanization rate (UR), population density (PD), reclamation rate (RR), and water resource utilization rate (WRUR)—were selected as influencing factors. A Tobit model was constructed to elucidate the driving mechanisms behind the evolution of the WLR coupling coordination degree (CCD) in WJP. The results indicate the following: (1) From a temporal perspective, the coupling coordination degree of WLR in WJP has shown a year-on-year increase from 2006 to 2020, transitioning from a moderate imbalance to intermediate coordination, reflecting a trend of continuous improvement. (2) Regarding spatial distribution, the overall center of gravity of water and land resource coupling coordination remained relatively stable between 2006 and 2020; however, the direction of distribution gradually shifted from the northeast to the southwest and then from the northwest to the southeast. (3) The AAT, PD, and RR from 2006 to 2020 were all statistically significant at p < 0.01. Notably, the RR positively influences the CCD of WLR, whereas the AAT and PD exert a negative impact. In contrast, the UR and WRUR do not significantly affect the CCD of WLR. Full article