[Spatiotemporal Coupling Analysis of Urbanization and Ecosystem Services in Southeastern Fujian].

Revealing the spatiotemporal coupling relationship between urbanization and ecosystem services can help to clarify regional development differences, optimize the implementation path of urbanization, and improve the quality of ecosystem services. Taking southeastern Fujian, a region with a good ecological foundation and strong urbanization potential, as a case study, the levels of multidimensional urbanization systems and typical ecosystem services of this region in the years 2000, 2010, and 2020 were quantified using the index comprehensive evaluation method and the InVEST model. The Pearson correlation coefficient and the coupling coordination degree model were used to analyze the spatiotemporal coupling relationship between urbanization and ecosystem services, and suggestions for improving regional coordinated development were proposed. The results showed that： ① The comprehensive urbanization level in southeastern Fujian increased continuously, with an average annual growth rate of 7.3%, of which social urbanization was the fastest, followed by economic urbanization and population urbanization, and spatial urbanization was relatively backward. Ecosystem services tended to decline, especially food and water provision services, which decreased by 61.9% and 46.9%, respectively. The spatial distribution showed a mismatch pattern of "high urbanization level and weak ecosystem services" in the southeast coastal area and "low urbanization level and strong ecosystem services" in the northwest inland area. ② The correlation between urbanization and ecosystem services was mainly negative. The negative effect of economic and social urbanization on ecosystem services was weaker than that of population and spatial urbanization, with a clear weakening tendency. As population and spatial urbanization slowed down sharply and economic and social urbanization accelerated, the driving force of urbanization development gradually shifted from "quantitative increase" to "qualitative improvement." Thus, the decline of ecosystem services was alleviated. ③ Comprehensive urbanization and various ecosystem services experienced three stages of "imbalance-transition-reconciliation," with an average increase of 60.5% to 120.6% in the coupling coordination degree. However, highly coordinated regions remained scarce, indicating that there is still significant room for improvement. The relative relationship between urbanization and ecosystem services evolved from urbanization lag to ecosystem services lag. The fluctuation problem of backward coupling coordination level caused by excessive urbanization had initially appeared in the southeastern coastal area. Therefore, in future construction, southeastern Fujian should improve economic quality and social benefits； strengthen the overall management, protection, and restoration of ecological space； and enhance the order and stability of the coordinated development of urbanization and ecosystem services.

Functional Characterization of the First Bona Fide Phytoene Synthase in Red Algae from Pyropia yezoensis.

The formation of phytoene by condensing two geranylgeranyl diphosphate molecules catalyzed by phytoene synthase (PSY) is the first committed and rate-limiting step in carotenoid biosynthesis, which has been extensively investigated in bacteria, land plants and microalgae. However, this step in macroalgae remains unknown. In the present study, a gene encoding putative phytoene synthase was cloned from the economic red alga Pyropia yezoensis-a species that has long been used in food and pharmaceuticals. The conservative motifs/domains and the tertiary structure predicted using bioinformatic tools suggested that the cloned PyPSY should encode a phytoene synthase; this was empirically confirmed by pigment complementation in E. coli. This phytoene synthase was encoded by a single copy gene, whose expression was presumably regulated by many factors. The phylogenetic relationship of PSYs from different organisms suggested that red algae are probably the progeny of primary endosymbiosis and plastid donors of secondary endosymbiosis.

Impacts of MnO2 on tomato (Lycopersicon esculentum Mill.) growth: A study with MnO2-amended organic fertilizer.

Manganese dioxide (MnO2), as a catalyst in composting processes, can accumulate in soil over multiple fertilizations. However, its impact on crop growth remains to be explored. In this study, a pot experiment was conducted to investigate the impacts of MnO2 on the tomato plant performance across various growth stages. Results showed that MnO2 reduced the plant height, leaf number and length by 35.53 %, 27.61 %, and 37.00 %, respectively, and decreased the fruit weight (23.16 %) and sugar-acid ratio (29.7 %) of fruits compared to the MnO2-free control. The adverse impacts of MnO2 on plant growth might be attributed to the inhibition of microbial activity in soil reflected by the reduction of soil urease (9.30 %) and acid phosphatase (12.52 %) activities, which decreased the efficiency of nutrients conversion and uptake. The decrease of nutrient elements in roots resulted in oxidative stress in the plant, inhibiting the plasma membrane H+-ATPase activity thereby reducing the translocation of nutrients (e.g., calcium, magnesium, and phosphorus) translocation from roots to leaves. Furthermore, the phytohormones indolebutyric acid, gibberellin, and jasmonic acid of leaves were disturbed. This study reveals the risks associated with the application of MnO2-containing organic fertilizers.

H2O2-triggered CO release based on porphyrinic covalent organic polymers for photodynamic/gas synergistic therapy.

A novel H2O2-responsive carbon monoxide nanogenerator was designed by effectively encapsulating a manganese carbonyl prodrug into porphyrinic covalent organic polymers for realizing the combined CO gas and photodynamic therapy under near infrared light irradiation.

Plantaginis semen ameliorates diabetic kidney disease via targeting the sphingosine kinase 1/sphingosine-1-phosphate pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Plantaginis Semen (PS) is widely utilized as a common herb in several Asian countries, particularly China, due to its diuretic, anti-hypertensive, anti-hyperlipidemic, and anti-hyperglycemic properties. Furthermore, it is acknowledged for its ability to mitigate renal complications associated with metabolic syndrome. Despite its extensive usage, there is limited systematic literature elucidating its therapeutic mechanisms, thus emphasizing the necessity for comprehensive investigations in this field. AIM: This study aims to comprehensively evaluate the therapeutical potential of PS in treating diabetic kidney disease (DKD) and to elucidate the underlying mechanisms through in vivo and in vitro models. METHODS: The main composition of PS were characterized using the UPLC-QTOF-MS method. For the in vivo investigation, a mouse model mediated by streptozocin (STZ) associated with a high-fat diet (HFD) and unilateral renal excision was established. The mice were split into 6 groups (n = 8): control group (CON group), DKD group, low-dose of Plantago asiatica L. seed extract group (PASE-L group, 3 g/kg/d), medium-dose of PASE group (PASE-M, 6 g/kg/d), high-dose of PASE group (PASE-H, 9 g/kg/d), and positive drug group (valsartan, VAS group, 12 mg/kg/d). After 8 weeks of treatment, the damage induced by DKD was evaluated by using relevant parameters of urine and blood. Furthermore, indicators of inflammation and factors associated with the SphK1-S1P signaling pathway were investigated. For the in vitro study, the cell line HBZY-1 was stimulated by high glucose (HG), they were then co-cultured with different concentrations of PASE, and the corresponding associated inflammatory and sphingosine kinase 1/sphingosine-1-phosphate (SphK1-S1P) factors were examined. RESULTS: A total of 59 major components in PS were identified, including flavonoids, iridoids, phenylethanol glycosides, guanidine derivatives, and fatty acids. In the mouse model, PS was found to significantly improve body weight, decrease fasting blood glucose (FBG) levels, increased glucose tolerance and insulin tolerance, improved kidney-related markers compared to the DKD group, pathological changes in the kidneys also improved dramatically. These effects showed a dose-dependent relationship, with higher PASE concentrations yielding significantly better outcomes than lower concentrations. However, the effects of the low PASE concentration were not evident for some indicators. In the cellular model, the high dose of PASE suppressed high glucose (HG) stimulated renal mesangial cell proliferation, suppressed inflammatory factors and NF-κB, and decreased the levels of fibrillin-1(FN-1) and collagen IV(ColIV). CONCLUSION: Our results indicate that PS exerts favorable therapeutic effects on DKD, with the possible mechanisms including the inhibition of inflammatory pathways, suppression of mRNA levels and protein expressions of SphK1 and S1P, consequently leading to reduced overexpression of FN-1 and ColIV, thereby warranting further exploration.

[Effects of Land Use Change on Soil Aggregate Stability and Soil Aggregate Organic Carbon in Karst Area of Southwest China].

Investigating the relationship of soil aggregate stability with the organic carbon in the aggregate and its response to land use change is conducive to the estimation of soil carbon sink potential, improvement of rocky desertification, and rational land use in karst areas of Southwest China. In order to explore the effects of land use change on the composition and stability of soil aggregate stability as well as the content of aggregate organic carbon, the soil (0-30 cm) of five land use types (secondary forest, pomelo forest, paddy field, pepper forest, and dry land) was selected as the research object. The characteristics and correlation of soil aggregate components and organic carbon under different land use patterns were obtained, and the contribution of soil aggregates to the change in organic carbon after land use change was calculated. The results showed that the macroaggregates in the surface soil (0-15 cm) of the secondary forest, pomelo forest, and paddy field were 63.32%, 52.38%, and 47.77%, respectively, which were significantly higher than that of dry land (23.70%), as was also seen in the lower layer (15-30 cm). The geometric mean diameter (GMD) and mean weight diameter (MWD) of soil aggregates in the secondary forest, pomelo forest, and paddy field were significantly higher than those in dry land. In the surface soil, the organic carbon of the secondary forest and paddy field was significantly higher than that of other land use patterns. By contrast, in the lower soil layer, only the organic carbon of the paddy field was significantly higher than that of the others. Under different land use patterns, the organic carbon content of aggregates followed the same order of macroaggregates > microaggregates > silt and clay, indicating that macroaggregates allowed soil organic carbon to accumulate, whereas silt and clay did the opposite. According to correlation analysis, the content of soil macroaggregates was significantly positively correlated with GMD, MWD, and soil aggregate organic carbon, suggesting that the increase in soil macroaggregates could improve the stability of soil aggregates and store more soil organic carbon. Further, as land use change may have significantly affected the soil aggregate, moderate development of forestry and paddy cultivation is suggested to improve the soil carbon sequestration potential in the karst area of Southwest China.

Tailoring Charge Separation in ZnIn2S4@CdS Hollow Nanocages for Simultaneous Alcohol Oxidation and CO2 Reduction under Visible Light.

Artificial photosynthesis provides a sustainable strategy for producing usable fuels and fine chemicals and attracts broad research interest. However, conventional approaches suffer from low reactivity or low selectivity. Herein, we demonstrate that photocatalytic reduction of CO2 coupled with selective oxidation of aromatic alcohol into corresponding syngas and aromatic aldehydes can be processed efficiently and fantastically over the designed S-scheme ZnIn2S4@CdS core-shell hollow nanocage under visible light. In the ZnIn2S4@CdS heterostructure, the photoexcited electrons and holes with weak redox capacities are eliminated, while the photoexcited electrons and holes with powder redox capacities are separated spatially and preserved on the desired active sites. Therefore, even if there are no cocatalysts and no vacancies, ZnIn2S4@CdS exhibits high reactivity. For instance, the CO production of ZnIn2S4@CdS is about 3.2 and 3.4 times higher than that of pure CdS and ZnIn2S4, respectively. More importantly, ZnIn2S4@CdS exhibits general applicability and high photocatalytic stability. Trapping agent experiments, 13CO2 isotopic tracing, in situ characterizations, and theoretical calculations reveal the photocatalytic mechanism. This study provides a new strategy to design efficient and selective photocatalysts for dual-function redox reactions by tailoring the active sites and regulating vector separation of photoexcited charge carriers.

Enhancing phosphorus source apportionment in watersheds through species-specific analysis.

Phosphorus (P) is a pivotal element responsible for triggering watershed eutrophication, and accurate source apportionment is a prerequisite for achieving the targeted prevention and control of P pollution. Current research predominantly emphasizes the allocation of total phosphorus (TP) loads from watershed pollution sources, with limited integration of source apportionment considering P species and their specific implications for eutrophication. This article conducts a retrospective analysis of the current state of research on watershed P source apportionment models, providing a comprehensive evaluation of three source apportionment methods, inventory analysis, diffusion models, and receptor models. Furthermore, a quantitative analysis of the impact of P species on watersheds is carried out, followed by the relationship between P species and the P source apportionment being critically clarified within watersheds. The study reveals that the impact of P on watershed eutrophication is highly dependent on P species, rather than absolute concentration of TP. Current research overlooking P species composition of pollution sources may render the acquired results of source apportionment incapable of assessing the impact of P sources on eutrophication accurately. In order to enhance the accuracy of watershed P pollution source apportionment, the following prospectives are recommended: (1) quantifying the P species composition of typical pollution sources; (2) revealing the mechanisms governing the migration and transformation of P species in watersheds; (3) expanding the application of traditional models and introducing novel methods to achieve quantitative source apportionment specifically for P species. Conducting source apportionment of specific species within a watershed contributes to a deeper understanding of P migration and transformation, enhancing the precise of management of P pollution sources and facilitating the targeted recovery of P resources.

Current trends and prospects of surgical techniques for hepatoblastoma.

Hepatoblastoma, a common extracranial malignant solid tumor in childhood, is often detected at an advanced stage and is difficult to treat surgically. Despite the availability of multiple comprehensive treatments that can be combined with surgery, hepatoblastoma treatment outcomes remain poor. Surgery is the main treatment strategy for hepatoblastoma, but it faces many challenges, including tumor attachment to surrounding tissues, tumor wrapping or invading of vital organs and tissues, the presence of giant or multiple tumors, distant metastasis, the formation of a tumor thrombus, and significant surgical trauma. In this review, we discuss recent research advances and propose potential strategies for overcoming these challenges. Such strategies may improve the rate of hepatoblastoma resection and local control in children, as well as reduce complications and trauma.

Effects of the Million Hearts Model on Myocardial Infarctions, Strokes, and Medicare Spending: A Randomized Clinical Trial.

Importance: The Million Hearts Model paid health care organizations to assess and reduce cardiovascular disease (CVD) risk. Model effects on long-term outcomes are unknown. Objective: To estimate model effects on first-time myocardial infarctions (MIs) and strokes and Medicare spending over a period up to 5 years. Design, Setting, and Participants: This pragmatic cluster-randomized trial ran from 2017 to 2021, with organizations assigned to a model intervention group or standard care control group. Randomized organizations included 516 US-based primary care and specialty practices, health centers, and hospital-based outpatient clinics participating voluntarily. Of these organizations, 342 entered patients into the study population, which included Medicare fee-for-service beneficiaries aged 40 to 79 years with no previous MI or stroke and with high or medium CVD risk (a 10-year predicted probability of MI or stroke [ie, CVD risk score] ≥15%) in 2017-2018. Intervention: Organizations agreed to perform guideline-concordant care, including routine CVD risk assessment and cardiovascular care management for high-risk patients. The Centers for Medicare & Medicaid Services paid organizations to calculate CVD risk scores for Medicare fee-for-service beneficiaries. CMS further rewarded organizations for reducing risk among high-risk beneficiaries (CVD risk score ≥30%). Main Outcomes and Measures: Outcomes included first-time CVD events (MIs, strokes, and transient ischemic attacks) identified in Medicare claims, combined first-time CVD events from claims and CVD deaths (coronary heart disease or cerebrovascular disease deaths) identified using the National Death Index, and Medicare Parts A and B spending for CVD events and overall. Outcomes were measured through 2021. Results: High- and medium-risk model intervention beneficiaries (n = 130 578) and standard care control beneficiaries (n = 88 286) were similar in age (median age, 72-73 y), sex (58%-59% men), race (7%-8% Black), and baseline CVD risk score (median, 24%). The probability of a first-time CVD event within 5 years was 0.3 percentage points lower for intervention beneficiaries than control beneficiaries (3.3% relative effect; adjusted hazard ratio [HR], 0.97 [90% CI, 0.93-1.00]; P = .09). The 5-year probability of combined first-time CVD events and CVD deaths was 0.4 percentage points lower in the intervention group (4.2% relative effect; HR, 0.96 [90% CI, 0.93-0.99]; P = .02). Medicare spending for CVD events was similar between the groups (effect estimate, -$1.83 per beneficiary per month [90% CI, -$3.97 to -$0.30]; P = .16), as was overall Medicare spending including model payments (effect estimate, $2.11 per beneficiary per month [90% CI, -$16.66 to $20.89]; P = .85). Conclusions and Relevance: The Million Hearts Model, which encouraged and paid for CVD risk assessment and reduction, reduced first-time MIs and strokes. Results support guidelines to use risk scores for CVD primary prevention. Trial Registration: ClinicalTrials.gov Identifier: NCT04047147.

Cytokine and chemokine map of peripheral specific immune cell subsets in Parkinson's disease.

Peripheral immune cells play a vital role in the development of Parkinson's disease (PD). However, their cytokine and chemokine secretion functions remain unclear. Therefore, we aimed to explore the cytokine and chemokine secretion functions of specific immune cell subtypes in drug-naïve patients with PD at different ages of onset. We included 10 early-onset and 10 late-onset patients with PD and age-matched healthy controls (HCs). We used mass cytometry to select specific immune cell subsets and evaluate intracellular cytokine and chemokine expression. Statistical tests included t-tests, analysis of variance, bivariate correlation analysis, and linear regression analysis. Compared with HCs, patients with PD exhibited significantly decreased intracellular pro-inflammatory cytokines and chemokines in selected clusters (e.g., tumor necrosis factor (TNF)-α, interleukin (IL)-8, IL-1ß, and CC-chemokine ligand (CCL)17). Specific cytokines and cell clusters were associated with clinical symptoms. TNF-α played an important role in cognitive impairment. Intracellular TNF-α levels in the naïve CD8+ T-cell cluster C16 (CD57- naïve CD8+ T) and natural killer (NK) cell cluster C32 (CD57- CD28- NK) were negatively correlated with Montreal Cognitive Assessment scores. The C16 cluster affected cognitive function and motor symptoms. Increased TNF-α and decreased interferon-γ expression in C16 correlated with increased Unified Parkinson's Disease Rating Scale III scores in patients with PD. In summary, we developed a more detailed cytokine and chemokine map of peripheral specific CD8+ T cell and NK cell subsets, which revealed disrupted secretory function in patients with PD and provided unique clues for further mechanistic exploration.

Nuclear DJ-1 Regulates DNA Damage Repair via the Regulation of PARP1 Activity.

DNA damage and defective DNA repair are extensively linked to neurodegeneration in Parkinson's disease (PD), but the underlying molecular mechanisms remain poorly understood. Here, we determined that the PD-associated protein DJ-1 plays an essential role in modulating DNA double-strand break (DSB) repair. Specifically, DJ-1 is a DNA damage response (DDR) protein that can be recruited to DNA damage sites, where it promotes DSB repair through both homologous recombination and nonhomologous end joining. Mechanistically, DJ-1 interacts directly with PARP1, a nuclear enzyme essential for genomic stability, and stimulates its enzymatic activity during DNA repair. Importantly, cells from PD patients with the DJ-1 mutation also have defective PARP1 activity and impaired repair of DSBs. In summary, our findings uncover a novel function of nuclear DJ-1 in DNA repair and genome stability maintenance, and suggest that defective DNA repair may contribute to the pathogenesis of PD linked to DJ-1 mutations.

Postoperative infectious complications following laparoscopic versus open hepatectomy for hepatocellular carcinoma: a multicenter propensity score analysis of 3876 patients.

OBJECTIVES: Hepatocellular carcinoma (HCC) is a common indication for hepatectomy that is often complicated by postoperative complication. The authors sought to investigate the relationship between the open with laparoscopic approach of hepatectomy and incidences of postoperative infectious complications. PATIENTS AND METHODS: Using a multicenter database, HCC patients who underwent laparoscopic hepatectomy (LH) or open hepatectomy (OH) were reviewed and analyzed. Propensity score matching (PSM), inverse probability of treatment weight (IPTW), and multivariate logistic regression analyses were utilized to assess the association of the operative approach with postoperative infectious complications, including incisional surgical site infection (SSI), organ/space SSI, and remote infection (RI). RESULTS: Among 3876 patients, 845 (21.8%) and 3031 (78.2%) patients underwent LH and OH, respectively. The overall incidence of infection was 6.9 versus 14.6% among patients who underwent LH versus OH, respectively ( P <0.001). Of note, the incidences of incisional SSI (1.8 vs. 6.3%, P <0.001), organ/space SSI (1.8 vs. 4.6%, P <0.001), and RI (3.8 vs. 9.8%, P <0.001) were all significantly lower among patients who underwent LH versus OH. After PSM (6.9, 1.8, 1.8, and 3.8% vs. 18.5, 8.4, 5.2, and 12.8%, respectively) and IPTW (9.5, 2.3, 2.1, and 5.5% vs. 14.3, 6.3, 4.5, and 9.8%, respectively), LH remained associated with statistically lower incidences of all types of infectious complications. After adjustment for other confounding factors on multivariate analyses, LH remained independently associated with lower incidences of overall infection, incisional SSI, organ/space SSI, and RI in the overall, PSM, and IPTW cohorts, respectively. CONCLUSION: Compared with open approach, laparoscopic approach was independently associated with lower incidences of postoperative infectious complications following hepatectomy for HCC.

DNA Damage-Mediated Neurotoxicity in Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease around the world; however, its pathogenesis remains unclear so far. Recent advances have shown that DNA damage and repair deficiency play an important role in the pathophysiology of PD. There is growing evidence suggesting that DNA damage is involved in the propagation of cellular damage in PD, leading to neuropathology under different conditions. Here, we reviewed the current work on DNA damage repair in PD. First, we outlined the evidence and causes of DNA damage in PD. Second, we described the potential pathways by which DNA damage mediates neurotoxicity in PD and discussed the precise mechanisms that drive these processes by DNA damage. In addition, we looked ahead to the potential interventions targeting DNA damage and repair. Finally, based on the current status of research, key problems that need to be addressed in future research were proposed.

Parkin regulates microglial NLRP3 and represses neurodegeneration in Parkinson's disease.

Microglial hyperactivation of the NOD-, LRR-, and pyrin domain-containing 3 (NLRP3) inflammasome contributes to the pathogenesis of Parkinson's disease (PD). Recently, neuronally expressed NLRP3 was demonstrated to be a Parkin polyubiquitination substrate and a driver of neurodegeneration in PD. However, the role of Parkin in NLRP3 inflammasome activation in microglia remains unclear. Thus, we aimed to investigate whether Parkin regulates NLRP3 in microglia. We investigated the role of Parkin in NLRP3 inflammasome activation through the overexpression of Parkin in BV2 microglial cells and knockout of Parkin in primary microglia after lipopolysaccharide (LPS) treatment. Immunoprecipitation experiments were conducted to quantify the ubiquitination levels of NLRP3 under various conditions and to assess the interaction between Parkin and NLRP3. In vivo experiments were conducted by administering intraperitoneal injections of LPS in wild-type and Parkin knockout mice. The Rotarod test, pole test, and open field test were performed to evaluate motor functions. Immunofluorescence was performed for pathological detection of key proteins. Overexpression of Parkin mediated NLRP3 degradation via K48-linked polyubiquitination in microglia. The loss of Parkin activity in LPS-induced mice resulted in excessive microglial NLRP3 inflammasome assembly, facilitating motor impairment, and dopaminergic neuron loss in the substantia nigra. Accelerating Parkin-induced NLRP3 degradation by administration of a heat shock protein (HSP90) inhibitor reduced the inflammatory response. Parkin regulates microglial NLRP3 inflammasome activation through polyubiquitination and alleviates neurodegeneration in PD. These results suggest that targeting Parkin-mediated microglial NLRP3 inflammasome activity could be a potential therapeutic strategy for PD.

In Vitro Digestion and Fecal Fermentation of Low-Gluten Rice and Its Effect on the Gut Microbiota.

Low-gluten rice is part of a special diet for chronic kidney disease patients, but its digestive mechanism in the gastrointestinal tract is unclear. In this study, low-gluten rice (LGR), common rice (CR), and rice starch (RS) were used as experimental samples, and their digestion and bacterial fermentation were simulated using an in vitro gastrointestinal reactor to investigate the mechanism of the effect of LGR on human health. The starch digestibility of CR was higher than that of LGR, with statistically significant differences. LGR has growth-promoting and metabolic effects on Akkermansia muciniphila. Among the beneficial metabolites, the concentration of short-chain fatty acids (SCFAs) from LGR reached 104.85 mmol/L, an increase of 44.94% (versus RS) and 25.33% (versus CR). Moreover, the concentration of lactic acid reached 18.19 mmol/L, an increase of 60.55% (versus RS) and 25.28% (versus CR). Among the harmful metabolites, the concentration of branched-chain fatty acids (BCFAs) in LGR was 0.29 mmol/L and the concentration of ammonia was 2.60 mmol/L, which was 79.31% and 16.15% lower than CR, respectively. A significant increase in the concentration of the beneficial intestinal bacteria Bacteroides and Bifidobacterium occurred from LGR. The 16s rDNA sequencing showed that the abundance of the Bacteroidetes and Firmicutes increased and the abundance of the Proteobacteria and Fusobacteria decreased. Thus, LGR has positive effects on digestion and gut microbiota structure and metabolism in humans.

Elevated serum anti-Saccharomyces cerevisiae antibody accompanied by gut mycobiota dysbiosis as a biomarker of diagnosis in patients with de novo Parkinson disease.

BACKGROUND AND PURPOSE: Intestinal inflammation and gut microbiota dysbiosis contribute to Parkinson disease (PD) pathogenesis, and growing evidence suggests associations between inflammatory bowel diseases (IBD) and PD. Considered as markers of chronic gastrointestinal inflammation, elevated serum anti-Saccharomyces cerevisiae antibody (ASCA) levels, against certain gut fungal components, are related to IBD, but their effect on PD is yet to be investigated. METHODS: Serum ASCA IgG and IgA levels were measured using an enzyme-linked immunosorbent assay, and the gut mycobiota communities were investigated using ITS2 sequencing and analyzed using the Qiime pipeline. RESULTS: The study included 393 subjects (148 healthy controls [HCs], 140 with PD, and 105 with essential tremor [ET]). Both serum ASCA IgG and IgA levels were significantly higher in the PD group than in the ET and HC groups. Combining serum ASCA levels and the occurrence of constipation could discriminate patients with PD from controls (area under the curve [AUC] = 0.81, 95% confidence interval [CI] = 0.76-0.86) and from patients with ET (AUC = 0.85, 95% CI = 0.79-0.89). Furthermore, the composition of the gut fungal community differed between the PD and HC groups. The relative abundances of Saccharomyces cerevisiae, Aspergillus, Candida solani, Aspergillus flavus, ASV601_Fungi, ASV866_Fungi, and ASV755_Fungi were significantly higher in the PD group, and enriched Malassezia restricta was found in the HC group. CONCLUSIONS: Our study identified elevated serum ASCA levels and enriched gut Saccharomyces cerevisiae in de novo PD.

Pharmacogenomics-a New Frontier for Individualized Treatment of Parkinson's Disease.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease with a significant public health burden. It is characterized by the gradual degeneration of dopamine neurons in the central nervous system. Although symptomatic pharmacological management remains the primary therapeutic method for PD, clinical experience reveals significant inter-individual heterogeneity in treatment effectiveness and adverse medication responses. The mechanisms behind the observed interindividual variability may be elucidated by investigating the role of genetic variation in human-to-human variances in medication responses and adverse effects. OBJECTIVE: This review aims to explore the impact of gene polymorphism on the efficacy of antiparkinsonian drugs. The identification of factors associated with treatment effectiveness variability might assist the creation of a more tailored pharmacological therapy with higher efficacy, fewer side outcomes, and cheaper costs. METHODS: In this review, we conducted a thorough search in databases such as PubMed, Web of Science, and Google Scholar, and critically examined current discoveries on Parkinson's disease pharmacogenetics. The ethnicity of the individuals, research methodologies, and potential bias of these studies were thoroughly compared, with the primary focus on consistent conclusions. RESULTS: This review provides a summary of the existing data on PD pharmacogenetics, identifies its limitations, and offers insights that may be beneficial for future research. Previous studies have investigated the impact of gene polymorphism on the effectiveness and adverse effects of levodopa. The trendiest genes are the COMT gene, DAT gene, and DRD2 gene. However, limited study on other anti-Parkinson's drugs has been conducted. CONCLUSION: Therefore, In order to develop an individualized precision treatment for PD, it is an inevitable trend to carry out multi-center, prospective, randomized controlled clinical trials of PD pharmacogenomics covering common clinical anti-PD drugs in large, homogeneous cohorts.

Impact of cognition-related single nucleotide polymorphisms on brain imaging phenotype in Parkinson's disease.

Multiple single nucleotide polymorphisms may contribute to cognitive decline in Parkinson's disease. However, the mechanism by which these single nucleotide polymorphisms modify brain imaging phenotype remains unclear. The aim of this study was to investigate the potential effects of multiple single nucleotide polymorphisms on brain imaging phenotype in Parkinson's disease. Forty-eight Parkinson's disease patients and 39 matched healthy controls underwent genotyping and 7T magnetic resonance imaging. A cognitive-weighted polygenic risk score model was designed, in which the effect sizes were determined individually for 36 single nucleotide polymorphisms. The correlations between polygenic risk score, neuroimaging features, and clinical data were analyzed. Furthermore, individual single nucleotide polymorphism analysis was performed to explore the main effects of genotypes and their interactive effects with Parkinson's disease diagnosis. We found that, in Parkinson's disease, the polygenic risk score was correlated with the neural activity of the hippocampus, parahippocampus, and fusiform gyrus, and with hippocampal-prefrontal and fusiform-temporal connectivity, as well as with gray matter alterations in the orbitofrontal cortex. In addition, we found that single nucleotide polymorphisms in α-synuclein (SNCA) were associated with white matter microstructural changes in the superior corona radiata, corpus callosum, and external capsule. A single nucleotide polymorphism in catechol-O-methyltransferase was associated with the neural activities of the lingual, fusiform, and occipital gyri, which are involved in visual cognitive dysfunction. Furthermore, DRD3 was associated with frontal and temporal lobe function and structure. In conclusion, imaging genetics is useful for providing a better understanding of the genetic pathways involved in the pathophysiologic processes underlying Parkinson's disease. This study provides evidence of an association between genetic factors, cognitive functions, and multi-modality neuroimaging biomarkers in Parkinson's disease.

Effect analysis of vertebroplasty combined with posterior decompression and internal fixation in the treatment of spinal metastases with neurological symptoms / 国际外科学杂志

Objective:To analyze the efficacy of vertebroplasty combined with posterior decompression and internal fixation in the treatment of spinal metastases with neurological symptoms.Methods:This study was a retrospective analysis of 32 cases with neurological symptoms caused by spinal metastatic tumor in the Department of Orthopedics, Beijing Friendship Hospital, Capital Medical University from June 2016 to January 2022. All 32 patients (20 males, 12 females) aged between 39 to 85 years were enrolled in this study, with a mean age of (64.8±11.9) years. Surgery time, bleeding volume, modified Tokuhashi score, spinal instability neoplastic score (SINS) were collected. The visual analogue score (VAS), Oswestry disability index (ODI), Karnofsky performance scale (KPS) and American spinal cord injury association (ASIA) score before surgery, 1 month after surgery, 3 months after surgery and 6 months after surgery were collected and analyzed. Measurement data with normal distribution were represented as mean±standard deviation( ± s), and the comparison before and after surgery was conducted using repeated-measures analysis of variance test. Measurement data with skewed distribution were represented as M( Q1, Q3). Results:All 32 patients were followed up for 6 months. The operation time was (209.6±49.0) min, and the blood loss was (462.9±298.3) mL. 14 patients(43.8%) were treated with blood transfusion. The modified Tokuhashi score was 8.09±2.89, and the SINS was 8.81±1.97. The VAS score before surgery, postoperative 1, 3, 6 months were 7.47±0.98, 3.87±0.87, 2.91±0.73 and 2.34±0.60, respectively. ODI score before surgery, postoperative 1, 3, 6 months were 79.13±9.50, 39.14±6.31, 34.43±6.42 and 31.08±4.80, respectively. KPS score before surgery, postoperative 1, 3, 6 months were 49.69±14.70, 64.68±15.02, 71.88±12.81 and 75.63±10.76, respectively. The ASIA grading at 6 months follow-up was improved compared to preoperative baseline. Postoperative complications occurred in 4 cases, including nerve root injury (1 case), bone cement leakage in paravertebral soft tissue (1cases), bone cement leakage in paravertebral vein(1case) and acute thoracic epidural hematoma (1case).Conclusion:Vertebroplasty combined with posterior decompression and internal fixation can effectively relieve pain, relieve the compression of spinal cord and nerve, recover nerve functions, and improve the quality of life of patients with spinal metastatic tumor.