Interactions between dissolved organic matter with different molecular weights and nonylphenol in surface water bodies.

Dissolved organic matter (DOM) has a complex composition, which can interact with various pollutants and affect the removal of pollutants. Therefore, a thorough understanding of the interaction between the encccvironmental hormone nonylphenol (NP) and DOM is crucial for environmental impact and development. In this study, the interaction was investigated by means of excitation emission matrix (EEM) fluorescence spectroscopy, UV-Vis spectroscopy, FT-IR spectroscopy, nuclear magnetic resonance (NMR) and complex model analysis. The interaction between different MW DOM and NP was verified by the spectral characterization data. According to the characterization analysis, the main components of DOM in water samples were proteinoid (C1, C2, C4) with MW < 1 k Da, and their binding capacity (log Ka value) and binding site number (n) showed the maximum values (3.37, 3.24, 3.26; 0.81, 1.22, 0.52). For the humus like substance (C3) with larger molecular weight, the log Ka value and the number of binding points n increased with increasing molecular weight, and the maximum values were 3.13 and 0.31, respectively. It can be seen that low molecular weight proteins have strong binding ability and binding sites with NP, and high molecular weight humus also have strong binding ability. Overall, the interaction between DOM and NP has molecular weight dependence and heterogeneity. The purpose of this study is to deeply understand the interaction characteristics of different MW DOM with NP, and to provide theoretical support and reference for the study of the removal effects of NP pollutants.

Population dynamics and its relationship with functional traits in different succession stages of temperate mixed coniferous broad-leaved forest in Northeast China.

Functional traits regulate plant response to environmental changes, with consequences on population dynamics. However, how plant functional traits impact population dynamics, including growth, mortality, and recruitment, remains elusive in temperate forests across different successional stages. In this study, we compiled data on population dynamics and eight functional traits, encompassing hydraulic, wood, and leaf traits, from 35 species commonly found in a secondary poplar-birch forest and a broad-leaved Korean pine forest in Northeast China. We quantified the intrinsic relationships between plant population dynamics and assessed how plant functional traits influenced these dynamics. The results demonstrated a gradual increase in the correlation among population dynamics as forest succession progressed. In the secondary forest, tree growth rate and mortality rate were negatively correlated, while growth-death rate and growth-recruitment rate were not related. Conversely, in the broad-leaved Korean pine forest, there was a significant negative correlation between tree growth rate and mortality rate, as well as between growth rate and recruitment rate, while tree mortality rate positively correlated with recruitment rate. Additionally, functional traits effectively predicted population dynamics, but the predictive ability varied across successional stages. Functional traits, particularly xylem hydraulic traits (e.g., Huber value) and anatomical traits (e.g., mean xylem conduit diameter), were stronger predictors of tree growth, mortality, and recruitment rates at the late successional stage compared with the early stage. These findings indicated that population dynamics and functional traits exhibited strong regularity in the late successional stage of broad-leaved Korean pine forests.

An anthracene-containing crown ether: synthesis, host-guest properties and modulation of solid state luminescence.

Organic solid state vapochromic materials are of great significance for the development of supramolecular chemistry and materials science. Herein, we synthesize a crown ether derivative (An34C10) containing two anthracene units and construct new crown ether-based vapochromic host-guest co-crystals. Due to the presence of anthracene, An34C10 not only shows good fluorescence properties but also displays mechanochromism. Single crystal structural analysis, powder X-ray diffraction and differential scanning calorimetry experiments demonstrate that the transformation between different stacking modes of An34C10 is responsible for mechanochromism. In addition, An34C10 can complex with 1,2,4,5-tetracyanobenzene (TCNB) to form host-guest complex (An34C10@TCNB) co-crystals. Because organic solvent fuming alters charge-transfer interactions in An34C10@TCNB, the fluorescence of the co-crystals can be turned on and off by 4-methylpyridine and chloroform vapors, respectively, realizing selective detection with opposite emission outputs. Meanwhile, the stimuli-responsive properties of An34C10 and An34C10@TCNB possess good cycling performance. This work provides a new strategy for the construction of organic solid state luminescent materials.

CircLIFRSA/miR-1305/PTEN axis attenuates malignant cellular processes in non-small cell lung cancer by regulating AKT phosphorylation.

BACKGROUND: Non-small cell lung cancer (NSCLC) is typically diagnosed at advanced stages, which limits the effectiveness of therapeutic interventions. The present study aimed to explore the role of the newly identified circLIFRSA in the PTEN/AKT signaling pathway and its involvement in the malignant processes of NSCLC. METHODS: CircLIFRSA expression was identified through microarray analysis, and its levels in NSCLC samples were quantified by RT-qPCR. The impact of circLIFRSA on cell growth, proliferation, apoptosis, and cell cycle were evaluated by MTT assay, colony formation assay, and flow cytometry. Additionally, Western blotting was employed to analyze the expression of PTEN and phosphorylated AKT (pAKT) in NSCLC cells. RESULTS: The expression of circLIFRSA was found to be significantly reduced in NSCLC cells and tissues. This downregulation correlated with various clinicopathological characteristics and indicated its potential as an early diagnostic biomarker for NSCLC. Importantly, circLIFRSA was shown to inhibit cell growth and proliferation while promoting apoptosis in NSCLC cells. Mechanically, circLIFRSA was found to attenuate the malignant processes of NSCLC cells via the miR-1305/PTEN axis and the suppression of AKT phosphorylation. CONCLUSIONS: These findings indicate that circLIFRSA/miR-1305/PTEN axis attenuates malignant processes by regulating AKT phosphorylation, and provide new insights into the potential of circLIFRSA as a biomarker for early diagnosis and as a promising therapeutic target in NSCLC.

Self-Assembled Triangular Prismatic Cages with Kinetic Inertness.

Two triangular prismatic cages were synthesized by combining a trishydrazide and two bisformyl precursors in strongly acidic water, where the dynamic nature of hydrazone was turned ON. An anionic guest was used as the template to drive the cage formation. Performing counterion exchange removed both the template and the Brønsted acid. The removal of the latter afforded the cages' kinetic inertness by turning OFF the reversibility of hydrazone. The cages can thus be used for recognizing various guests in water without observable degradation, driven by the hydrophobic effect. Upon being accommodated within the cage cavities, an anthracene derivative was protected from UV-stimulated oxidation, which would occur otherwise in the bulk solution without the protection from the host.

Determinants of tree population temporal stability in a temperate mixed forest over a gradient of nitrogen addition.

Nitrogen (N) deposition is a significant threat to the functioning of forests and negatively impacts the delivery of forest goods and services. Contemporary management approaches seek to adapt forests to such N-deposition stressors, but to date how plant populations in natural forests respond to N deposition and what factors determine the contrasting responses among populations are still unclear. Here, we investigated the impact of N-addition (control: 0 kg ha-1 yr-1; low: 25 kg ha-1 yr-1; medium: 50 kg ha-1 yr-1; high: 75 kg ha-1 ha yr-1) on tree population temporal stability and how initial tree size, mycorrhizal type, and leaf N content (LNC; as a surrogate for functional trait composition) mediate tree population responses to N-addition in a Korean pine and mixed broadleaved dominated temperate forest in northern China. We quantified tree species population temporal stability as the ratio of mean to standard deviation of the year-by-year stem increments recorded in individual trees from 2015 to 2022 experimental period. The results showed different temporal stabilities of tree species among four N-addition levels, with the highest population stability observed within the high N-addition plots. Furthermore, initial tree size had significantly (p < 0.001) positive effects on population temporal stability. The effect of LNC and initial tree size were also contingent on the level of N applied. Specifically, increase in tree population LNC reduced population temporal stability in all plots where N was added. Our results imply that retention of large-sized trees and species with resource-conservative strategies (e.g., low LNC) could enhance forest stability under N deposition.

A Pillar[5]arene-Containing Metal-Organic Framework for Rapid and Highly Capable Adsorption of a Mustard Gas Simulant.

Mustard gas causes irreversible damage upon inhalation or contact with the human body. Consequently, the development of adsorbents for effective interception of mustard gas at low concentrations and high flow rates is an urgent necessity. Here we report a stable porous pillar[5]arene-containing metal-organic framework (MOF) based on zirconium (EtP5-Zr-scu), demonstrating that embedding pillar[5]arene units in MOFs can provide specific binding sites for efficient adsorption of a mustard gas simulant, 2-chloroethyl ethyl sulfide (CEES). EtP5-Zr-scu achieves a higher capacity and more rapid adsorption compared to its counterpart without embedded pillar[5]arene units (H4tcpt-Zr-scu) and perethylated pillar[5]arene (EtP5) alone. Single crystal X-ray diffraction and solid-state nuclear magnetic resonance reveal that the enhanced performance of EtP5-Zr-scu is derived from the host-guest complexation between CEES and pillar[5]arene moieties. Moreover, breakthrough experiments confirmed that the interception performance of EtP5-Zr-scu against CEES (800 ppm, 120 mL/min) was significantly improved (566 min/g) compared with H4tcpt-Zr-scu (353 min/g) and EtP5 (0.873 min/g), attributed to the integration of open channels with specific recognition sites. This work marks a significant advancement in the development of macrocycle-incorporated crystalline framework materials with recognition sites for the efficient capture of guest molecules.

A Pillararene-Based Cavitand: Synthesis and Solid-State Capsular Assemblies Induced by Linear Alkanes with Specific Lengths.

Herein, a novel pillararene-based cavitand with fixed planar chirality was synthesized by the SuFEx reaction. As demonstrated by single crystal X-ray analysis, host-guest capsules involving this cavitand and linear alkanes with specific lengths are observed in the solid state. The formation of each capsule is driven by hydrogen bonding interactions between a linear alkane molecule and two cavitand molecules, as well as noncovalent interactions between the two cavitand molecules in this capsule.

Disturbance history, neighborhood crowding and soil conditions jointly shape tree growth in temperate forests.

Understanding how different mechanisms act and interact in shaping communities and ecosystems is essential to better predict their future with global change. Disturbance legacy, abiotic conditions, and biotic interactions can simultaneously influence tree growth, but it remains unclear what are their relative contributions and whether they have additive or interactive effects. We examined the separate and joint effects of disturbance intensity, soil conditions, and neighborhood crowding on tree growth in 10 temperate forests in northeast China. We found that disturbance was the strongest driver of tree growth, followed by neighbors and soil. Specifically, trees grew slower with decreasing initial disturbance intensity, but with increasing neighborhood crowding, soil pH and soil total phosphorus. Interestingly, the decrease in tree growth with increasing soil pH and soil phosphorus was steeper with high initial disturbance intensity. Testing the role of species traits, we showed that fast-growing species exhibited greater maximum tree size, but lower wood density and specific leaf area. Species with lower wood density grew faster with increasing initial disturbance intensity, while species with higher specific leaf area suffered less from neighbors in areas with high initial disturbance intensity. Our study suggests that accounting for both individual and interactive effects of multiple drivers is crucial to better predict forest dynamics.

Host specificity of plant-associated bacteria is negatively associated with genome size and host abundance along a latitudinal gradient.

Host specialization plays a critical role in the ecology and evolution of plant-microbe symbiosis. Theory predicts that host specialization is associated with microbial genome streamlining and is influenced by the abundance of host species, both of which can vary across latitudes, leading to a latitudinal gradient in host specificity. Here, we quantified the host specificity and composition of plant-bacteria symbioses on leaves across 329 tree species spanning a latitudinal gradient. Our analysis revealed a predominance of host-specialized leaf bacteria. The degree of host specificity was negatively correlated with bacterial genome size and the local abundance of host plants. Additionally, we found an increased host specificity at lower latitudes, aligning with the high prevalence of small bacterial genomes and rare host species in the tropics. These findings underscore the importance of genome streamlining and host abundance in the evolution of host specificity in plant-associated bacteria along the latitudinal gradient.

Guest-induced narcissistic self-sorting in water via imine formation.

Two anionic tetrahedral cages were self-assembled as the only observable products in weakly basic water via imine condensation. The success of the high-yielding formation of the cages in water relies on (i) multivalency enhancing the stability of the imine bond and affording these cages water compatibility and (ii) a guest template with a complementary size and geometry that provides a hydrophobic driving force by occupying the corresponding cage cavity. When all four precursors, namely two trisaldehydes and two trisamines, were combined in water, narcissistic self-sorting occurred when both guest templates were present. In organic media where the hydrophobic effect is absent, narcissistic self-sorting did not occur in the analogous cage systems, confirming the importance of guest templates.

Emerging evidence of context-dependent synapse elimination by phagocytes in the CNS.

Precise synapse elimination is essential for the establishment of a fully developed neural circuit during brain development and higher function in adult brain. Beyond immune and nutrition support, recent groundbreaking studies have revealed that phagocytic microglia and astrocytes can actively and selectively eliminate synapses in normal and diseased brains, thereby mediating synapse loss and maintaining circuit homeostasis. Multiple lines of evidence indicate that the mechanisms of synapse elimination by phagocytic glia are not universal but rather depend on specific contexts and detailed neuron-glia interactions. The mechanism of synapse elimination by phagocytic glia is dependent on neuron-intrinsic factors and many innate immune and local apoptosis-related molecules. During development, microglial synapse engulfment in the visual thalamus is primarily influenced by the classic complement pathway, whereas in the barrel cortex, the fractalkine pathway is dominant. In Alzheimer's disease, microglia employ complement-dependent mechanisms for synapse engulfment in tauopathy and early ß-amyloid pathology, but microglia are not involved in synapse loss at late ß-amyloid stages. Phagocytic microglia also engulf synapses in a complement-dependent way in schizophrenia, anxiety, and stress. In addition, phagocytic astrocytes engulf synapses in a MEGF10-dependent way during visual development, memory, and stroke. Furthermore, the mechanism of a phenomenon that phagocytes selectively eliminate excitatory and inhibitory synapses is also emphasized in this review. We hypothesize that elucidating context-dependent synapse elimination by phagocytic microglia and astrocytes may reveal the molecular basis of synapse loss in neural disorders and provide a rationale for developing novel candidate therapies that target synapse loss and circuit homeostasis.

Age-Related Conservation in Plant-Soil Feedback Accompanied by Ectomycorrhizal Domination in Temperate Forests in Northeast China.

This study investigates the effects of forest aging on ectomycorrhizal (EcM) fungal community and foraging behavior and their interactions with plant-soil attributes. We explored EcM fungal communities and hyphal exploration types via rDNA sequencing and investigated their associations with plant-soil traits by comparing younger (~120 years) and older (~250 years) temperate forest stands in Northeast China. The results revealed increases in the EcM fungal richness and abundance with forest aging, paralleled by plant-soil feedback shifting from explorative to conservative nutrient use strategies. In the younger stands, Tomentella species were prevalent and showed positive correlations with nutrient availability in both the soil and leaves, alongside rapid increases in woody productivity. However, the older stands were marked by the dominance of the genera Inocybe, Hymenogaster, and Otidea which were significantly and positively correlated with soil nutrient contents and plant structural attributes such as the community-weighted mean height and standing biomass. Notably, the ratios of longer-to-shorter distance EcM fungal exploration types tended to decrease along with forest aging. Our findings underscore the integral role of EcM fungi in the aging processes of temperate forests, highlighting the EcM symbiont-mediated mechanisms adapting to nutrient scarcity and promoting sustainability in plant-soil consortia.

Evaluation of Molecular Residual Disease by a Fixed Panel in Resectable Colorectal Cancer.

PURPOSE: Molecular residual disease (MRD) is a promising biomarker in colorectal cancer (CRC) for prognosis and guiding treatment, while the whole-exome sequencing (WES) based tumor-informed assay is standard for evaluating MRD based on circulating tumor DNA (ctDNA). In this study, we assessed the feasibility of a fixed-panel for evaluating MRD in CRC. MATERIALS AND METHODS: Seventy-five patients with resectable stage I-III CRC were enrolled. Tumor tissues obtained by surgery, and preoperative and postoperative day 7 blood samples were collected. The ctDNA was evaluated using the tumor-agnostic and tumor-informed fixed assays, as well as the WES-based and panel-based personalized assays in randomly selected patients. RESULTS: The tumor-informed fixed assay had a higher preoperative positive rate than the tumor-agnostic assay (73.3% vs. 57.3%). The preoperative ctDNA status failed to predict disease-free survival (DFS) in either of the fixed assays, while the tumor-informed fixed assay-determined postoperative ctDNA positivity was significantly associated with worse DFS (hazard ratio [HR], 20.74; 95% confidence interval [CI], 7.19 to 59.83; p < 0.001), which was an independent predictor by multivariable analysis (HR, 28.57; 95% CI, 7.10 to 114.9; p < 0.001). Sub-cohort analysis indicated the WES-based personalized assay had the highest preoperative positive rate (95.1%). The two personalized assays and the tumor-informed fixed assay demonstrated same results in postoperative landmark (HR, 26.34; 95% CI, 6.01 to 115.57; p < 0.001), outperforming the tumor-agnostic fixed panel (HR, 3.04; 95% CI, 0.94 to 9.89; p=0.052). CONCLUSION: Our study confirmed the prognostic value of the ctDNA positivity at postoperative day 7 by the tumor-informed fixed panel. The tumor-informed fixed panel may be a cost-effective method to evaluate MRD, which warrants further studies in future.

Preserving shape details of pulse signals for video-based blood pressure estimation.

In recent years, imaging photoplethysmograph (iPPG) pulse signals have been widely used in the research of non-contact blood pressure (BP) estimation, in which BP estimation based on pulse features is the main research direction. Pulse features are directly related to the shape of pulse signals while iPPG pulse signals are easily disturbed during the extraction process. To mitigate the impact of pulse feature distortion on BP estimation, it is necessary to eliminate interference while retaining valuable shape details in the iPPG pulse signal. Contact photoplethysmograph (cPPG) pulse signals measured at rest can be considered as the undisturbed reference signal. Transforming the iPPG pulse signal to the corresponding cPPG pulse signal is a method to ensure the effectiveness of shape details. However, achieving the required shape accuracy through direct transformation from iPPG to the corresponding cPPG pulse signals is challenging. We propose a method to mitigate this challenge by replacing the reference signal with an average cardiac cycle (ACC) signal, which can approximately represent the shape information of all cardiac cycles in a short time. A neural network using multi-scale convolution and self-attention mechanisms is developed for this transformation. Our method demonstrates a significant improvement in the maximal information coefficient (MIC) between pulse features and BP values, indicating a stronger correlation. Moreover, pulse signals transformed by our method exhibit enhanced performance in BP estimation using different model types. Experiments are conducted on a real-world database with 491 subjects in the hospital, averaging 60 years of age.

Bone-derived PDGF-BB enhances hippocampal non-specific transcytosis through microglia-endothelial crosstalk in HFD-induced metabolic syndrome.

BACKGROUND: It is well known that high-fat diet (HFD)-induced metabolic syndrome plays a crucial role in cognitive decline and brain-blood barrier (BBB) breakdown. However, whether the bone-brain axis participates in this pathological process remains unknown. Here, we report that platelet-derived growth factor-BB (PDGF-BB) secretion by preosteoclasts in the bone accelerates neuroinflammation. The expression of alkaline phosphatase (ALPL), a nonspecific transcytosis marker, was upregulated during HFD challenge. MAIN BODY: Preosteoclast-specific Pdgfb transgenic mice with high PDGF-BB concentrations in the circulation recapitulated the HFD-induced neuroinflammation and transcytosis shift. Preosteoclast-specific Pdgfb knockout mice were partially rescued from hippocampal neuroinflammation and transcytosis shifts in HFD-challenged mice. HFD-induced PDGF-BB elevation aggravated microglia-associated neuroinflammation and interleukin-1ß (IL-1ß) secretion, which increased ALPL expression and transcytosis shift through enhancing protein 1 (SP1) translocation in endothelial cells. CONCLUSION: Our findings confirm the role of bone-secreted PDGF-BB in neuroinflammation and the transcytosis shift in the hippocampal region during HFD challenge and identify a novel mechanism of microglia-endothelial crosstalk in HFD-induced metabolic syndrome.

SLC20A1 is a prospective prognostic and therapy response predictive biomarker in head and neck squamous cell carcinoma.

BACKGROUND: SLC20A1, a prominent biomarker in several cancers, has been understudied in its predictive role in head and neck squamous cell carcinoma (HNSCC). METHODS: The Cancer Genome Atlas (TCGA) database was used to analyze HNSCC prognosis, SLC20A1 overexpression, and clinical characteristics. Quantitative real-time PCR and Western blot analysis confirmed SLC20A1 expression in HNSCC tissues. Cellular behaviors such as invasion, migration and proliferation were assessed using Transwell, wound healing and colony formation assays. Immune system data were obtained from the Tumor Immune Estimation Resource (TIMER) and CIBERSORT databases. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were used to explore biological parameters and pathways associated with SLC20A1 overexpression in HNSCC. RESULTS: In 499 HNSCC samples, SLC20A1 mRNA and protein expression were significantly higher than in 44 normal counterparts, confirmed by 24 paired samples. Patients were categorized based on SLC20A1 levels, survival status and overall survival. High SLC20A1 expression correlated with advanced T stage, increased risk scores and decreased survival. Stage, age and SLC20A1 expression emerged as independent predictive factors for HNSCC in univariate and multivariate analyses. SLC20A1 overexpression, which is associated with poor prognosis, may influence cell proliferation, migration, invasion, chemotherapy response, and the immune milieu. CONCLUSIONS: SLC20A1 overexpression in HNSCC, characterized by increased cellular invasion, migration and proliferation, is a potential prognostic biomarker and therapeutic response indicator.

Cancer-associated fibroblasts reprogram cysteine metabolism to increase tumor resistance to ferroptosis in pancreatic cancer.

Background: Pancreatic ductal adenocarcinoma (PDAC) is an insidious, rapidly progressing malignancy of the gastrointestinal tract. Due to its dense fibrous stroma and complex tumor microenvironment, neither of which is sensitive to radiotherapy, pancreatic adenocarcinoma is one of the malignancies with the poorest prognosis. Therefore, detailed elucidation of the inhibitory microenvironment of PDAC is essential for the development of novel therapeutic strategies. Methods: We analyzed the association between cancer-associated fibroblasts (CAFs) and resistance to ferroptosis in PDAC using conditioned CAF medium and co-culture of pancreatic cancer cells. Abnormal cysteine metabolism was observed in CAFs using non-targeted metabolomics analysis with liquid chromatography-tandem mass spectrometry (LC-MS/MS). The regulatory effects of cysteine were investigated in PDAC cells through measurement of cell cloning, cell death, cell function, and EdU assays. The effects of exogenous cysteine intake were examined in a mouse xenograft model and the effects of the cysteine pathway on ferroptosis in PDAC were investigated by western blotting, measurement of glutathione and reactive oxygen species levels, among others. Results: It was found that CAFs played a critical role in PDAC metabolism by secreting cysteine, which could increase tumor resistance to ferroptosis. A previously unrecognized function of the sulfur transfer pathway in CAFs was identified, which increased the extracellular supply of cysteine to support glutathione synthesis and thus inducing ferroptosis resistance. Cysteine secretion by CAFs was found to be mediated by the TGF-ß/SMAD3/ATF4 signaling axis. Conclusion: Taken together, the findings demonstrate a novel metabolic relationship between CAFs and cancer cells, in which cysteine generated by CAFs acts as a substrate in the prevention of oxidative damage in PDAC and thus suggests new therapeutic targets for PDAC.

The Impact of 90 Parkinson's Disease-Risk Single Nucleotide Polymorphisms on Urinary Bis(monoacylglycerol)phosphate Levels in the Prodromal and PD Cohorts.

Parkinson's disease (PD) is a common neurodegenerative disorder with a prolonged prodromal phase. Higher urinary bis(monoacylglycerol)phosphate (BMP) levels associate with LRRK2 (leucine-rich repeat kinase 2) and GBA1 (glucocerebrosidase) mutations, and are considered as potential noninvasive biomarkers for predicting those mutations and PD progression. However, their reliability has been questioned, with inadequately investigated genetics, cohorts, and population. In this study, multiple statistical hypothesis tests were employed on urinary BMP levels and sequences of 90 PD-risk single nucleotide polymorphisms (SNPs) from Parkinson's Progression Markers Institution (PPMI) participants. Those SNPs were categorized into four groups based on their impact on BMP levels in various cohorts. Variants rs34637584 G/A and rs34637584 A/A (LRRK2 G2019S) were identified as the most relevant on increasing urinary BMP levels in the PD cohort. Meanwhile, rs76763715 T/T (GBA1) was the primary factor elevating BMP levels in the prodromal cohort compared to its T/C and C/C variants (N370S) and the PD cohort. Proteomics analysis indicated the changed transport pathways may be the reasons for elevated BMP levels in prodromal patients. Our findings demonstrated that higher urinary BMP levels alone were not reliable biomarkers for PD progression or gene mutations but might serve as supplementary indicators for early diagnosis and treatment.