Comprehensive analysis of clinical and biological features in Parkinson's disease associated with the LRRK2 G2019S mutation: Data from the PPMI study.

The Parkinson's Progression Marker Initiative (PPMI) aims to identify biomarkers for Parkinson's disease (PD) risk, onset, and progression. This study focuses on the G2019S missense mutation in the LRRK2 gene, which is associated with hereditary and sporadic PD. Utilizing data from the PPMI database, we conducted an analysis of baseline clinical characteristics, as well as serum and cerebrospinal fluid levels in two groups: patients with PD with the G2019S mutation (PD + G2019S) and patients with PD without the mutation (PD-G2019S). Multiple linear regression and longitudinal analysis were performed, controlling for confounding factors. Compared to the PD-G2019S group, the PD + G2019S group showed more obvious initial motor dysfunction-higher baseline Movement Disorder Society-Sponsored Revision of the Unified Parkinson Disease Rating Scale (MDS-UPDRS) scores (false discovery rate [FDR]-adjusted p < 0.001), but progressed more slowly. Mechanism of Coordinated Access and activities of daily living (ADL) scores were lower at baseline (FDR-adjusted p < 0.001), whereas Scales for Outcomes of Parkinson's Disease (SCOPA)-Thermoregulatory (FDR-adjusted p = 0.015) scores were higher, emphasizing the increase of non-motor symptoms associated with LRRK2-G2019S mutation. During the follow-up period, the motor and non-motor symptoms changed dynamically with time, and there were longitudinal differences in the scores of MDS-UPDRS (FDR-adjusted PI = 0.013, PII = 0.008, PIV < 0.001), Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (FDR-adjusted p = 0.027), SCOPA-Thermoregulatory (FDR-adjusted p = 0.021), and ADL (FDR-adjusted p = 0.027) scale scores. PD associated with the LRRK2 G2019S mutation demonstrated more severe symptoms at baseline but slower progression. Motor complications and thermoregulatory disorders were more pronounced.

Pharmacological Effects of Urolithin A and Its Role in Muscle Health and Performance: Current Knowledge and Prospects.

Urolithin A (UA) is a naturally occurring compound derived from the metabolism of gut microbiota, which has attracted considerable research attention due to its pharmacological effects and potential implications in muscle health and performance. Recent studies have demonstrated that Urolithin A exhibits diverse biological activities, encompassing anti-inflammatory, antioxidant, anti-tumor, and anti-aging properties. In terms of muscle health, accumulating evidence suggests that Urolithin A may promote muscle protein synthesis and muscle growth through various pathways, offering promise in mitigating muscle atrophy. Moreover, Urolithin A exhibits the potential to enhance muscle health and performance by improving mitochondrial function and regulating autophagy. Nonetheless, further comprehensive investigations are still warranted to elucidate the underlying mechanisms of Urolithin A and to assess its feasibility and safety in human subjects, thereby advancing its potential applications in the realms of muscle health and performance.

Presence of different microplastics promotes greenhouse gas emissions and alters the microbial community composition of farmland soil.

Microplastics (MPs) are regarded as potential persistent organic pollutants owing to their small size and low degradability. However, the effect of MP pollution on greenhouse gas (GHG) emissions from farmland soil is yet unclear. Therefore, a series of microcosm experiments were set up using polyvinyl chloride (PVC), polypropylene (PP), polyethylene (PE), polystyrene (PS), and polyester (PET) at concentrations of 0.25 %, 2 %, and 7 % (w/w). Each treatment had three replicates. This experiment was carried out to verify the effect of MP pollution on greenhouse gas (GHG) emissions from farmland soil. The results showed that the addition of MPs significantly promoted the emissions of the three main GHGs, including nitrous oxide (N2O), carbon dioxide (CO2), and methane (CH4). Especially, PE may cause most GHG emissions which would contribute to climate warming when its pollution concentration increased. In addition, different doses and types of MPs could affect microbial community structure. These findings of this present study may provide a scientific and practical reference for the prevention and control of MPs pollution and risk assessment of global climate change caused by MPs.

Associations of striatal dopamine transporter binding with motor and non-motor symptoms in early Parkinson's disease.

Dopamine transporter (DAT) imaging is an in vivo tool to assess presynaptic dopaminergic function in the clinical practices of Parkinson's disease (PD). Current clinical practices focused on qualitatively visual interpretation of DAT imaging, whereas quantitative analyses are potentially more helpful when monitoring the progression of PD. Previous cross-sectional studies indicated certain motor and non-motor features were associated with striatal DAT binding, whereas limited data were reported in terms of the longitudinal correlation between clinical features of PD with striatal DAT binding. The purpose of our study is to clarify current and longitudinal correlations between striatal DAT binding and clinical measures. A total of 352 untreated PD individuals and 167 healthy controls with complete baseline clinical measures and neuroimaging data were identified from the Parkinson's Progression and Markers Initiative (PPMI) database. Patients with PD underwent DAT imaging at the screening visit and following months 12, 24, and 48. Multiple linear regression models and linear mixed-effect models were respectively conducted to investigate the cross-sectional and longitudinal correlation between clinical characteristics and DAT binding. Associations between changes in clinical characteristics and changes in DAT binding were further evaluated and the Spearman rank correlation coefficients were reported. In the cross-sectional analysis, baseline striatal DAT binding was significantly associated with the Hoehn and Yahr scale, the Movement Disorder Society-Sponsored Revision of the Unified Parkinson Disease Rating Scale (MDS-UPDRS) scores, the rigidity scores, and the axial scores in PD individuals (false discovery rate [FDR]-adjusted p = 0.0017 for all above). Patients who developed freezing of gait had lower striatal DAT binding (FDR-adjusted p = 0.0161). Healthy controls who had higher tremor scores and suffered more severe olfactory dysfunction had lower striatal DAT binding (FDR-adjusted p = 0.0257 for all above). Longitudinal analysis indicated that baseline severity of rapid-eye-movement sleep behavior disorder was significantly associated with longitudinal striatal DAT binding in patients with PD (FDR-adjusted p = 0.0120). Furthermore, changes in MDS-UPDRS scores and the State-Trait Anxiety Inventory (STAI) scores demonstrated significant correlations with changes in striatal DAT binding over 4 years (p = 0.005 and p = 0.032, respectively). Our findings clarified quantitative associations between certain motor and non-motor features with current and future striatal dopamine binding, suggesting the feasibility of using DAT images as a progression predictive marker for PD. Further studies are needed to investigate correlations between different regional dopamine binding with specific clinical features.

The associations of cerebrospinal fluid biomarkers with cognition, and rapid eye movement sleep behavior disorder in early Parkinson's disease.

Background: In Parkinson's disease (PD), levels of cerebrospinal fluid (CSF) biomarkers and progression of non-motor symptoms are associated, but the specifics are not yet clear. Objective: The aim of this study was to investigate the associations of non-motor symptoms with CSF biomarkers in PD. Materials and methods: We assessed 487 individuals from the Parkinson's Progression Markers Initiative (PPMI), consisting of 155 healthy controls (HCs) and 332 individuals with PD. Patients with PD were grouped according to non-motor symptoms and compared CSF α-synuclein (α-syn), amyloid-beta 1-42 (Aß1-42), and total tau (t-tau) levels. Multiple linear regressions were used in baseline analysis and linear mixed-effects models in longitudinal analysis. Analyses of mediating effects between cognition and CSF biomarkers were also performed. Results: At baseline, PD patients with cognitive impairment (PDCI) exhibited significantly lower CSF α-syn (ß = -0.1244; P = 0.0469), Aß (ß = -0.1302; P = 0.0447), and t-tau (ß = -0.1260; P = 0.0131) levels than PD patients without cognitive impairment (PDCU). Moreover, a faster decline of α-syn (ß = -0.2152; P = 0.0374) and Aß (ß = -0.3114; P = 0.0023) and a faster rise of t-tau (ß = -0.1534; P = 0.0274) have been found in longitudinal analysis. The Aß positive group showed an earlier decline in cognitive performance (ß = -0.5341; P = 0.0180) compared with the negative Aß group in both analyses. In addition, we found that PD patients with probable rapid eye movement sleep behavior disorder (pRBD) showed decreased CSF α-syn (ß = -0.1343; P = 0.0033) levels. Finally, mediation analysis demonstrated that olfactory function partially mediated the relationship between cognition and CSF biomarkers levels. Conclusion: Our study shows that CSF biomarkers are associated with cognition at baseline and longitudinally. Cognitive impairment is more severe in patients with a heavier Aß burden. CSF α-syn decreased in PD patients with pRBD. This study suggests that early recognition of the increased risk of non-motor symptoms is important for disease surveillance and may be associated with the pathological progression of CSF markers.

Physiological response and oxidative stress of grass carp (Ctenopharyngodon idellus) under single and combined toxicity of polystyrene microplastics and cadmium.

The harm of microplastics (MPs) to aquatic ecosystems is caused by their stable and non-degradable properties. Additionally, the pollutants such as heavy metals in the water are easy to be adsorbed on their surface with their small particle size and large specific surface area, resulting in environmental pollution. Therefore, the study on the mixture toxicity of MPs and heavy metals has theoretical significance for the risk assessment of aquatic ecosystems. In the present study, 10 nm polystyrene (PS) and cadmium (Cd) were used, and their individual and mixture acute toxicities on grass carp (Ctenopharyngodon idellus) were examined. The results indicated that the mortality of the fish increased with the concentration from 10 mg L-1 to 20 mg L-1, and the existence of PS-MPs elevated the Cd concentrations in the fish and accelerated the death. Whether the Cd and/or the PS-MPs concentrations caused varying degrees of damage to the gills, kidney, liver, and muscles of the grass carp, especially under the highest concentrations (20 mg L-1 Cd + 300 µg L-1 PS-MPs). Moreover, low concentrations of PS-MPs alone (30 µg L-1 PS-MPs) significantly increased the superoxide dismutase (SOD) activity in the kidney and liver, reaching 12.43% and 14.38%, respectively (P < 0.05). The peroxidase (POD) activity was increased only in the kidney, up to 25.95% (P < 0.05). Also, significant reductions in SOD and POD activities were observed in the combination of high concentration of Cd (20 mg L-1) and 300 µg L-1 PS-MPs (P < 0.05). To the best of our knowledge, there are few studies on the impact of combined toxicity of PS-MPs and Cd on grass carp under laboratory conditions. Therefore, these findings may provide a theoretical guarantee for pollution prevention and control in the aquatic ecosystem.

Prevalence and associated factors of dry skin among older inpatients in hospitals and nursing homes: A multicenter cross-sectional study.

BACKGROUND/OBJECTIVES: Dry skin is a common skin problem in older persons. Aim of this study was to determine the prevalence, associated factors of dry skin in older inpatients. DESIGN: A multicenter cross-sectional study was designed and conducted. SETTINGS/PARTICIPANTS: On 31 March and 29 May in 2021 two days, fifty hospitals and two nursing homes in China participated in the study. In total, 33,769 participants were included. The mean age was 73.2 (SD 8.9) years. METHODS: A whole-body skin examination and associated data collection were performed by 1067 trained nurses based on a standardized data form and methods. Descriptive and univariable analyses and multivariable logistic regressions were conducted. RESULTS: In total, 11,602 participants had dry skin with a prevalence of 34.4%, mainly located on the upper and lower limbs with very severe skin dryness, 21.2% of the participants reported that their dry skin had pruritus, and 12.5% complained that sleep was affected by dry skin. The stronger predictor for dry skin was nursing homes (OR 5.07, 95% CI 3.99-6.45). Other predictors for dry skin were age, male sex, nutrition, lower activity level, skincare dependence, renal and pulmonary impairment, diabetes mellitus, varicose veins, cardiovascular diseases and Parkinsonism, diuretics, statins and antibiotics. The predictive model of area under ROC curve was 0.628(95% CI 0.622-0.634). CONCLUSIONS: The prevalence of dry skin among Chinese older patients was at high level and was associated with multiple factors. Persons with skin dryness have a higher proportion of skin itching and poor sleep. REGISTRATION: It has been registered in the Chinese Clinical Trial Registry (ChiCTR2100042893).

LncRNA SNHG12 promotes the malignant progression of melanoma by targeting miR-199b.

Background: Melanoma is a type of tumor caused by the malignant transformation of melanocytes, and has a high degree of malignancy. Small nucleolar RNA host gene 12 (SNHG12) plays an important role in a variety of cancers, but its role in melanoma and its mechanisms are still unclear. In this study, we measured the expression of SNHG12 and explored the molecular mechanisms involved in melanoma. Methods: We detected the expression level of SNHG12 in melanoma cell lines, and explored the effect of SNHG12 on the proliferation, migration, and invasion of melanoma cells in vitro. Mechanistic studies explored the regulation of downstream genes by SNHG12. Results: Overexpression of SNHG12 was found in melanoma cell lines, and SNHG12 promoted the proliferation, migration, and invasion of melanoma cells. MiR-199b is a target gene of SNHG12, which was expressed at low levels in melanoma cell lines, and SNHG12 regulated melanoma cell proliferation, migration, and invasion through miR-199b. We also revealed that SNHG12 promoted the expression of the target genes of miR-199b, namely ETS1, PXN, JAG1, and DDR1. Conclusions: SNHG12 is highly expressed in melanoma, and promotes the expression of ETS1, PXN, JAG1, and DDR1 through targeted regulation of miR-199b, thereby promoting the proliferation, migration, and invasion of melanoma cells.

The molecular mechanisms of quality difference for Alpine Qingming green tea and Guyu green tea by integrating multi-omics.

Introduction: Harvest time represents one of the crucial factors concerning the quality of alpine green tea. At present, the mechanisms of the tea quality changing with harvest time have been unrevealed. Methods: In the current study, fresh tea leaves (qmlc and gylc) and processed leaves (qmgc and gygc) picked during Qingming Festival and Guyu Festival were analyzed by means of sensory evaluation, metabolomics, transcriptomic analysis, and high-throughput sequencing, as well as their endophytic bacteria (qm16s and gy16s). Results: The results indicated qmgc possessed higher sensory quality than gygc which reflected from higher relative contents of amino acids, and soluble sugars but lower relative contents of catechins, theaflavins, and flavonols. These differential metabolites created features of light green color, prominent freshness, sweet aftertaste, and mild bitterness for qmgc. Discussion: Flavone and flavonol biosynthesis and phenylalanine metabolism were uncovered as the key pathways to differentiate the quality of qmgc and gygc. Endophytic bacteria in leaves further influence the quality by regulating the growth of tea trees and enhancing their disease resistance. Our findings threw some new clues on the tea leaves picking to pursue the balance when facing the conflicts of product quality and economic benefits.

Dioscin induces ferroptosis and synergistic cytotoxicity with chemotherapeutics in melanoma cells.

In this study, we evaluated the anti-tumor effects of dioscin, a steroidal saponin, on melanoma cells. Dioscin significantly inhibited cell viability and induced cell death of melanoma cells in a time- and dose- dependent manner. Furthermore, dioscin increased the concentration of intracellular ferrous irons, MDA and ROS. This effect could be inhibited by L-g-glutamyl-p-nitroanilide (GPNA), compound 968 and ferroptosis inhibitor ferrostatin-1 (Fer-1). Furthermore, dioscin induced ferroptosis by affecting the expression of transferrin and ferroportin which are regulators of intracellular levels of iron. Finally, dioscin in combination with various chemotherapeutic agents showed synergistic effects against melanoma cells. Our data suggested that dioscin exerted anti-tumor effects in melanoma cells by inducing ferroptosis. Dioscin alone or with other agents might be applied as a promising strategy to treat melanoma.

miR-495 inhibits proliferation, migration, and invasion and induces apoptosis via inhibiting PBX3 in melanoma cells.

BACKGROUND: Amounting evidence indicate that miRNAs play an important role in the development of various cancers. MiR-495 is a potential tumor suppressor in cancers, however its role in melanoma is still elusive. The study aimed to investigate the role of miR-495 and the underlying mechanisms in melanoma cells. METHODS: The levels of miR-495 in melanoma tissues and cell lines were measured by quantitative real-time polymerase chain reaction. Mimics of miR-495 was transfected into human melanoma cells A375 and MeWo. Cell viability of miR-495-transfected cells was assayed by MTT assay. Cell migration and invasion of miR-495 transfected cells were measured by wound healing assay and transwell assay, respectively. Nucleosome enzyme-linked immunosorbent assay was performed to measure the apoptosis induced by overexpression of miR-495. Luciferase reporter assays were performed to verify the interaction between miR-495 and its target PBX3. RESULTS: It was found that the expression levels of miR-495 were down-regulated in melanoma tissues and cells. Moreover, overexpression of miR-495 inhibited melanoma cell proliferation, migration and invasion in vitro. PBX3 was identified as a target for inhibition by miR-495 and was confirmed by luciferase assay, quantitative real-time polymerase chain reaction and western blot. We also indicated that silencing of PBX3 also repressed melanoma cell proliferation, migration and invasion in vitro. CONCLUSION: In summary, our findings demonstrated that miR-495 functions as a tumor suppressor in human melanoma via directly targeting PBX3.

[Blue-on-yellow perimetry in patients with primary open-angle glaucoma].

OBJECTIVE: To investigate the early changes of the blue-on-yellow (B/Y) perimetry in patients with early primary open-angle glaucoma(POAG). METHODS: Thirty-one cases (45 eyes) of POAG underwent the central 30 degrees field examination of B/Y as well as routine white-on-white (W/W). RESULT: No significant difference of mean index deficiency (MD) between B/Y and W/W perimetry was detected (P>0.05). However, there were marked changes in index GHT (glaucoma hemisphere test) and more defect points in B/Y visual field than those in W/W (P<0.01). CONCLUSION: B/Y perimetry might be more sensitive than W/W perimetry a potentially more and valuable method in detection of early POAG lesion.