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Background: Alterations in metabolites and metabolic pathways are thought to be important triggers of idiopathic pulmonary fibrosis (IPF), but our lack of a comprehensive understanding of this process has hampered the development of IPF-targeted drugs. Methods: To fully understand the metabolic profile of IPF, C57BL/6 J male mice were injected intratracheally with bleomycin so that it could be used to construct a mouse model of IPF, and lung tissues from 28-day and control IPF mice were analyzed by pathology and immunohistochemistry. In addition, serum metabolites from IPF mice were examined using LC-ESI-MS/MS, and the differential metabolites were analyzed for KEGG metabolic pathways and screened for biomarkers using machine learning algorithms. Results: In total, the levels of 1465 metabolites were detected, of which 104 metabolites were significantly altered after IPF formation. In IPF mouse serum, 52% of metabolite expression was downregulated, with lipids (e.g., GP, FA) and organic acids and their derivatives together accounting for more than 70% of the downregulated differentially expressed metabolites. In contrast, FA and oxidised lipids together accounted for 60% of the up-regulated differentially expressed metabolites. KEGG pathway enrichment analyses of differential metabolites were mainly enriched in the biosynthesis of unsaturated fatty acids, pentose phosphate pathway, and alanine, aspartate, and glutamate metabolism. Seven metabolites were screened by machine learning LASSO models and evaluated as ideal diagnostic tools by receiver operating characteristic curves (ROCs). Discussion: In conclusion, the serum metabolic disorders found to be associated with pulmonary fibrosis formation will help to deepen our understanding of the pathogenesis of pulmonary fibrosis.
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Toxoplasma gondii( T. gondii or Tg), is an obligatory intracellular parasite with humans as its intermediate hosts. In recent years, significant correlations between T. gondii infection and schizophrenia have been reported, including the possible mediating mechanisms. Currently, mechanisms and hypotheses focus on central neurotransmitters, immunity, neuroinflammation, and epigenetics; however, the exact underlying mechanisms remain unclear. In this article, we review the studies related to T. gondii infection and schizophrenia, particularly the latest research progress. Research on dopamine (DA) and other neurotransmitters, the blood-brain barrier, inflammatory factors, disease heterogeneity, and other confounders is also discussed. In addition, we also summarized the results of some new epidemiological investigations.
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Esquizofrenia , Toxoplasma , Toxoplasmosis , Esquizofrenia/parasitología , Esquizofrenia/etiología , Humanos , Toxoplasmosis/complicaciones , Toxoplasmosis/epidemiología , Toxoplasmosis/parasitología , AnimalesRESUMEN
Lignin, a renewable natural antioxidant and bacteriostat, holds promise as a versatile, cost-effective feed additive. However, traditional industrial lignin faces limitations, including low reactivity, poor uniformity, and unstable properties, necessitating chemical modification. Complex modification methods pose economic and toxicity challenges, so this study adopted a relatively simple alkali-catalyzed phenolization approach, using phenol, catechol, and pyrogallol to modify kraft lignin, and characterized the resulting products using various techniques. Subsequently, their antioxidant, antibacterial, adsorption properties for heavy metal ions and mycotoxins, growth-promoting properties, and antiviral abilities were assessed. The phenolation process led to lignin depolymerization and a notable increase in phenolic hydroxyl content, particularly in pyrogallol-phenolated lignin (Py-L), rising from 3.08 to 4.68 mmol/g. These modified lignins exhibited enhanced antioxidant activity, with over 99 % inhibition against E. coli and S. aureus, and remarkable adsorption capacities for heavy metal ions and mycotoxins. Importantly, Py-L improved the growth performance of mice and reduced influenza mortality. Furthermore, density functional theory calculations elucidated the mechanism behind the enhanced antioxidant properties. This study presents a promising avenue for developing versatile feed additives to address challenges related to animal feed antioxidant supplementation, bacterial control, and growth promotion.
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Alimentación Animal , Antioxidantes , Lignina , Lignina/química , Antioxidantes/química , Antioxidantes/farmacología , Animales , Ratones , Antibacterianos/farmacología , Antibacterianos/química , Escherichia coli/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Fenoles/química , Fenoles/farmacología , Staphylococcus aureus/efectos de los fármacos , Adsorción , Pirogalol/química , Pirogalol/farmacología , Metales Pesados/química , Micotoxinas/química , Micotoxinas/farmacologíaRESUMEN
Causal effect estimation of individual heterogeneity is a core issue in the field of causal inference, and its application in medicine poses an active and challenging problem. In high-risk decision-making domain such as healthcare, inappropriate treatments can have serious negative impacts on patients. Recently, machine learning-based methods have been proposed to improve the accuracy of causal effect estimation results. However, many of these methods concentrate on estimating causal effects of continuous outcome variables under binary intervention conditions, and give less consideration to multivariate intervention conditions or discrete outcome variables, thus limiting their scope of application. To tackle this issue, we combine the double machine learning framework with Light Gradient Boosting Machine (LightGBM) and propose a double LightGBM model. This model can estimate binary causal effects more accurately and in less time. Two cyclic structures were added to the model. Data correction method was introduced and improved to transform discrete outcome variables into continuous outcome variables. Multivariate Cyclic Double LightGBM model (MCD-LightGBM) was proposed to intelligently estimate multivariate treatment effects. A visual human-computer interaction system for heterogeneous causal effect estimation was designed, which can be applied to different types of data. This paper reports that the system improved the Logarithm of the Minimum Angle of Resolution (LogMAR) of visual acuity change after Vascular Endothelial Growth Factor (anti-VEGF) treatment in patients with diabetic macular degeneration. The improvement was observed in two clinical problems, from 0.05 to 0.33, and the readmission rate of diabetic patients after cure was reduced from 48.4% to 10.5%. The results above demonstrate the potential of the proposed system in predicting heterogeneous clinical drug treatment effects.
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This study investigated the effects of co-fermentation of T. delbrueckii and S. cerevisiae on the volatile composition and sensory characteristics of blueberry wines. Mixed fermentation led to higher levels of terpenes, higher alcohols, and esters compared to wines fermented with each yeast individually. Conversely, when T. delbrueckii were physically separated from S. cerevisiae in the double-compartment fermenter, contrasting outcomes emerged. The stronger fruity aroma induced by mixed fermentation were linked to higher ester concentrations, including isoamyl acetate, ethyl isovalerate, ethyl hexanoate, and diethyl succinate. The enhanced esters in mixed fermentation can be attributed to the upregulated alcohol acyltransferase activity and the expressions of ACC1, FAS2, ELO1 and ATF1 genes in late fermentation stage via the cell-cell contact between T. delbrueckii and S. cerevisiae. These findings can deepen the understanding of the interaction between non-Saccharomyces and S. cerevisiae in ester production, assisting wineries in effectively controlling wine aroma through mixed fermentations.
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Arándanos Azules (Planta) , Torulaspora , Vino , Saccharomyces cerevisiae/metabolismo , Fermentación , Vino/análisis , Torulaspora/metabolismo , Ésteres/análisisRESUMEN
Plant stomatal phenotype traits play an important role in improving crop water use efficiency, stress resistance and yield. However, at present, the acquisition of phenotype traits mainly relies on manual measurement, which is time-consuming and laborious. In order to obtain high-throughput stomatal phenotype traits, we proposed a real-time recognition network SLPA-Net for stomata localization and phenotypic analysis. After locating and identifying stomatal density data, ellipse fitting is used to automatically obtain phenotype data such as apertures. Aiming at the problems of small stomata and high similarity to background, we introduced ECANet to improve the accuracy of stoma and aperture location. In order to effectively alleviate the unbalance problem in bounding box regression, we replaced the Loss function with a more effective Focal EIoU Loss. The experimental results show that SLPA-Net has excellent performance in the migration generalization and robustness of stomata and apertures detection and identification, as well as the correlation between stomata phenotype data obtained and artificial data.
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Fenotipo , Estomas de Plantas , Estomas de Plantas/fisiología , Estomas de Plantas/genética , Biología Computacional/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Algoritmos , Redes Neurales de la ComputaciónRESUMEN
Polyelectrolytes have been widely applied in electrochemical devices. Understanding the polyelectrolyte/electrode interfaces is pivotal for polyelectrolyte-based applications. Here, we measured the electrochemical potential drop and the local activity of the mobile ion of H+ or OH- at the polyelectrolytes/Au interfaces by in situ electrochemical surface-enhanced Raman spectroscopy and voltammetry in three-electrode cells. We found that the potential dependences of the electrochemical potential drop in polyelectrolytes were smaller than that in conventional electrolyte solutions. The interfacial activity of H+ or OH- was much lower than that of bulk polyelectrolytes. The potential-dependent molecular dynamics simulations showed that the mobility of ionomers of polyelectrolytes in an electrostatic field was limited by a polymer matrix. These results suggested a characteristically thicker compact layer in the electrical double layer of a polyelectrolyte/electrode interface due to the accumulation of mobile H+ or OH- with a thicker hydration layer and immobile ionomers.
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This study aimed to improve the aroma quality of blueberry wine by employing cultivar selection and precise berry sorting. We conducted a comprehensive analysis of volatile profiles in blueberry wines derived from nine cultivars commonly cultivated in the middle region of China. 'Misty' and 'V3' blueberry wines exhibited pronounced floral aromas, closely linked to elevated terpenoid and phenylacetaldehyde content. 'Legacy' and 'Star' displayed a distinct fruity aroma profile attributed to the presence of ethyl 2-methylbutyrate, ethyl phenylacetate, and diethyl succinate. 'Jewel' featured an intense buttery aroma, correlated with higher concentrations of ethyl dodecanoate, ethyl decanoate, and ethyl octanoate. Subsequently, 'Misty' and 'Star', with distinct aroma profiles, were selected to further unravel the impact of berry size on blueberry wine aroma. The findings revealed that small berries significantly enhanced 'Misty' blueberry wines, increasing higher alcohol, ester, and terpenoid content, resulting in a more intense fruity and floral aroma. Interestingly, berry size had no discernible influence on 'Star' blueberry wine aroma. This study provides valuable insights into the enhancement of blueberry wine production, shedding light on the intricate interplay of cultivar selection, berry sorting, and their impact on the aromatic attributes of the final product.
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Objective: This randomized double-blinded clinical study is to investigate the clinical efficacy of per-paravertebral disk ozone injection combined with steroids in the treatment of patients with chronic discogenic low back pain (CDLBP). Methods: Group A (N = 60) received a per-paravertebral injection of a steroid mixture of 10 mL with pure oxygen 20 mL, while group B (N = 60) received a per-paravertebral injection of a steroid mixture of 10 mL combined with ozone 20 mL (30 µg/mL). Injections were administered once a week for 3 weeks, with a follow-up of 6 months. Clinical outcomes were assessed at week 1, month 3, and month 6 with the help of Visual Analog Scale (VAS) scores and Macnab efficacy evaluation. Results: The VAS score of both group A (1.65 vs. 6.87, p = 0.000) and group B (1.25 vs. 6.85, p = 0.000) at week 1 was significantly reduced compared to baseline. The effect was sustained at the 3- and 6-month follow-up periods (p < 0.05). Group B had significantly lower VAS scores at month 3 (1.53 vs. 3.82, p = 0.000) and month 6 (2.80 vs. 5.05, p = 0.000) compared to group A, respectively. Based on Macnab criteria, 95 and 96.7% of patients in groups A and B had good rates "excellent plus good" at week 1, respectively. Good rates were significantly higher in group B at month 3 (91.7 vs. 78.3%, p = 0.041) and month 6 (85.0 vs. 68.3%, p = 0.031) compared to group A, respectively. No serious adverse events were noted in both groups. Conclusion: Per-paravertebral injection of steroid and ozone combination resulted in better relief of CDLBP compared to pure oxygen plus steroid. Clinical Trial Registration: ChiCTR2100044434 https://www.chictr.org.cn/showproj.html?proj=121571.
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Blueberries with 20%, 30%, and 40% weight loss were used for winemaking, aiming to explore the feasibility of applying postharvest dehydration for improving blueberry wine aroma. Postharvest dehydration decreased the titratable acidity of blueberries and their resultant wines. Total anthocyanins and phenols in blueberries with 30% weight loss were increased by 25.9% and 16.1%, respectively, due to concentration effects, while further dehydration resulted in a decline. Similar trends were observed in blueberry wines. Moderate postharvest dehydration increased total terpenes, benzeneacetaldehyde and phenylethyl alcohol, ethyl butanoate, methyl salicylate, 1-hexanol, and γ-nonalactone content in blueberries and wines, which could enhance the floral, fruity, and sweet notes of blueberry wines. Wines made from blueberries under severe dehydration (40% weight loss) had the lowest overall aroma score, which was related to the higher content of 4-ethyl-phenol and 4-ethylguaiacol. In conclusion, moderate postharvest dehydration benefited the aroma enhancement of blueberry wine.
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Arándanos Azules (Planta) , Vino , Humanos , Vino/análisis , Antocianinas/análisis , Deshidratación , Odorantes/análisisRESUMEN
Unraveling the origin of Helmholtz capacitance is of paramount importance for understanding the interfacial structure and electrostatic potential distribution of electric double layers (EDL). In this work, we combined the methods of ab initio molecular dynamics and classical molecular dynamics and modeled electrified Cu(100)/electrolyte and graphene/electrolyte interfaces for comparison. It was proposed that the Helmholtz capacitance is composed of three parts connected in series: the usual solvent capacitance, water chemisorption induced capacitance, and Pauling repulsion caused gap capacitance. We found the Helmholtz capacitance of graphene is significantly lower than that of Cu(100), which was attributed to two intrinsic factors. One is that graphene has a wider gap layer at interface, and the other is that graphene is less active for water chemisorption. Finally, based on our findings, we provide suggestions for how to increase the EDL capacitance of graphene-based materials in future work, and we also suggest that the new understanding of the potential distribution across the Helmholtz layer may help explain some experimental phenomena of electrocatalysis.
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As an advance in hydrofunctionalization, we herein report that alcohols add to 1,3-dienes with high regio- and enantioselectivity. Using Ni-DuPhos, we access enantioenriched allylic ethers. Through the choice of solvent-free conditions, we control the reversibility of C-O bond formation. This work showcases a rare example of methanol as a reagent in asymmetric synthesis.
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Several studies showed the efficacy of Lycium barbarum polysaccharide (LBP) in diabetic animals and patients with type 2 diabetes mellitus (T2DM). However, the mechanism of LBP in alleviating T2DM based on glucagon-like peptide 1 (GLP1) has not been suitably elucidated. GLP1 is an important peptide that plays a role in blood glucose homeostasis. Inhibition of sodium/glucose cotransporter 1 (SGLT1) can result in a net increase in GLP1 release. We found that LBP could reduce SGLT1 expression. Thus, the effects of LBP on the first- and second-phase secretion of GLP1 were systematically assessed in vitro using STC1 cells and in vivo using diabetic KKAy mice. LBP could induce the first-phase secretion of GLP1 by stimulating calcium ion influx in vitro and by inhibiting alpha-glucosidase activity in vivo. Regulation of Gcg gene expression by modulating the Wnt/ß-catenin and cAMP/Epac pathways, as well as inhibition of alpha-glucosidase activity, was responsible for the second-phase secretion of GLP1. LBP could stimulate GLP1 secretion; however, dipeptidyl peptidase 4 (DPP4) activated by LBP might offset the second-phase secretion of GLP1. Thus, we suggest considering the simultaneous use of LBP and a DPP4 inhibitor to stimulate slow, continuous GLP1 secretion. Further studies are warranted for in-depth mechanistic information.
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Diabetes Mellitus Tipo 2 , Medicamentos Herbarios Chinos , Lycium , Ratones , Animales , Péptido 1 Similar al Glucagón/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , alfa-Glucosidasas , Hipoglucemiantes/farmacología , Lycium/metabolismoRESUMEN
Plant stomata phenotypic traits can provide a basis for enhancing crop tolerance in adversity. Manually counting the number of stomata and measuring the height and width of stomata obviously cannot satisfy the high-throughput data. How to detect and recognize plant stomata quickly and accurately is the prerequisite and key for studying the physiological characteristics of stomata. In this research, we consider stomata recognition as a multi-object detection problem, and propose an end-to-end framework for intelligent detection and recognition of plant stomata based on feature weights transfer learning and YOLOv4 network. It is easy to operate and greatly facilitates the analysis of stomata phenotypic traits in high-throughput plant epidermal cell images. For different cultivars, multi-scales, rich background features, high density, and small stomata object images, the proposed method can precisely locate multiple stomata in microscope images and automatically give phenotypic traits of stomata. Users can also adjust the corresponding parameters to maximize the accuracy and scalability of automatic stomata detection and recognition. Experimental results on actual data provided by the National Maize Improvement Center show that the proposed method is superior to the existing methods in high stomata automatic detection and recognition accuracy, low training cost, strong generalization ability.
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Procesamiento de Imagen Asistido por Computador , Estomas de Plantas , Procesamiento de Imagen Asistido por Computador/métodos , Fenotipo , Microscopía , Aprendizaje AutomáticoRESUMEN
This study showcases the first enantioselective hydroselenation of styrenes. Organoselenium building blocks are accessed with selectivity for the branched isomer. Through a Rh-hydride pathway, C-Se bonds can be forged with excellent regio- and enantiocontrol.
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Estirenos , Catálisis , Compuestos de Selenio , EstereoisomerismoRESUMEN
BACKGROUND: Altered metabolic pathways have recently been considered as potential drivers of idiopathic pulmonary fibrosis (IPF) for the study of drug therapeutic targets. However, our understanding of the metabolite profile during IPF formation is lacking. METHODS: To comprehensively characterize the metabolic disorders of IPF, a mouse IPF model was constructed by intratracheal injection of bleomycin into C57BL/6J male mice, and lung tissues from IPF mice at 7 days, 14 days, and controls were analyzed by pathology, immunohistochemistry, and Western Blots. Meanwhile, serum metabolite detections were conducted in IPF mice using LC-ESI-MS/MS, KEGG metabolic pathway analysis was applied to the differential metabolites, and biomarkers were screened using machine learning algorithms. RESULTS: We analyzed the levels of 1465 metabolites and found that more than one-third of the metabolites were altered during IPF formation. There were 504 and 565 metabolites that differed between M7 and M14 and controls, respectively, while 201 differential metabolites were found between M7 and M14. In IPF mouse sera, about 80% of differential metabolite expression was downregulated. Lipids accounted for more than 80% of the differential metabolite species with down-regulated expression. The KEGG pathway enrichment analysis of differential metabolites was mainly enriched to pathways such as the metabolism of glycerolipids and glycerophospholipids. Eight metabolites were screened by a machine learning random forest model, and receiver operating characteristic curves (ROC) assessed them as ideal diagnostic tools. CONCLUSIONS: In conclusion, we have identified disturbances in serum lipid metabolism associated with the formation of pulmonary fibrosis, contributing to the understanding of the pathogenesis of pulmonary fibrosis.
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Bleomicina , Fibrosis Pulmonar Idiopática , Animales , Biomarcadores , Bleomicina/toxicidad , Modelos Animales de Enfermedad , Glicerofosfolípidos , Humanos , Fibrosis Pulmonar Idiopática/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Espectrometría de Masas en TándemRESUMEN
BACKGROUND: Prostate cancer is a major disease impacting men's health worldwide. Peplau, who is known as "the mother of psychiatric society," developed an interpersonal relationship theory for nursing. Implementation of this theory in practice has been shown to positively impact patients' quality of life and reduce adverse symptoms after surgery. AIM: To investigate the effects of a nursing model based on Peplau's interpersonal relationship theory combined with bladder function training on patients with prostate cancer. METHODS: Eighty-nine patients with prostate cancer who underwent transurethral resection of the prostate (TURP) participated in this study. These patients were admitted to The First Affiliated Hospital of Soochow University or Dushu Lake Hospital Affiliated to Soochow University between January 2020 and April 2021. Patients were randomized into either the Peplau nursing group (n = 44) or a routine nursing group (n = 45). The routine nursing group received routine care and bladder function training, while the Peplau care group received care that integrated concepts from the Peplau interpersonal relationship theory as well as bladder function training. The urinary incontinence symptoms of the two groups were recorded, and the respective International Prostate Symptom Scores (IPSS), Functional Assessment of Chronic Illness Therapy- Spiritual Well-Being (FACIT-Sp) scores, and quality of life (QOL) scores for each group were compared before and after three months of nursing intervention. RESULTS: During the intervention period, the duration of urinary incontinence, frequency, number and amount of urinary incontinence were significantly greater in the routine nursing group compared to the Peplau care group (P < 0.05). The indicators of the routine nursing group were 7.13 ± 2.42 days, 8.23 ± 2.75 times, and 1.24 ± 0.42 L, while those of the Peplau care group were 4.74 ± 1.85 d, 4.21 ± 1.26 times, and 0.56 ± 0.11 L, respectively. After three months of intervention, the mean IPSS score of the routine nursing group was significantly reduced (P < 0.05), while the mean FACIT-Sp and QOL scores were significantly increased (P < 0.05). The mean IPSS score in the Peplau nursing group was significantly lower compared to the routine nursing group, while the FACIT-Sp and QOL scores were higher (P < 0.05). CONCLUSION: A nursing model based on Peplau's interpersonal relationship theory combined with bladder function training can significantly improve prostate function and urinary symptoms, resulting in the restoration of physiological function and improvement in the QOL of patients with prostate cancer following TURP.
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In the present paper, a new species of cynipid gall wasp, Andricuselodeoides Liu & Pang, is described from several provinces in southern China. The new species is closely related to the recently redescribed A.mairei (Kieffer, 1906). In addition to differences in adult and gall morphology, the new species is also readily separated by COI sequences, with a 6.2-8.9% genetic distance between populations of the new species and those of A.mairei. A contrasting difference in sex ratios was also observed between the two species, with A.elodeoides extremely female-biased (95.5-97.8% female) while A.mairei male-biased to more balanced (5.4-43.5% female). PCR screening for Wolbachia infection further revealed contrasting infection rates between populations of A.elodeoides and A.mairei: the Wolbachia infection rate was 0% in A.elodeoides and 100% in A.mairei. Cytoplasmic incompatibility induced by Wolbachia is proposed as a potential mechanism of speciation of the sympatric A.elodeoides and A.mairei.
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The convergent cross mapping (CCM) is a method to analyze causality of nonlinear time series variables. Different from the traditional linear system analysis method, CCM gets historical information based on their state space reconstruction. The presence of causality can be confirmed when the estimated values perform convergent with time series extension. Here, we introduced the develop-ment history of CCM and its advantages over the traditional Granger causality test, and elaborated the principle, algorithm process, and implementation approach. As a system analysis method aiming at the coupling relationship between variables from weak to moderate, CCM can effectively solve the complex causality among nonlinear multivariable in ecosystems. When it is applied to the causality analysis of multi-point time series variables with spatial information, the spatial autocorrelation among points should be fully considered and combined with the method that can remove the spatial correlation between variables and sequences, so as to ensure more accurate causality analysis using CCM and more convincing results.