Distinct effects of SDC3 and FGFRL1 on selective neurodegeneration in AD and PD.

Alzheimer's disease (AD) and Parkinson's disease (PD) are age-dependent neurodegenerative disorders. There is a profound neuronal loss in the basal forebrain cholinergic system in AD and severe dopaminergic deficiency within the nigrostriatal pathway in PD. Swedish APP (APPSWE ) and SNCAA53T mutations promote Aß generation and α-synuclein aggregation, respectively, and have been linked to the pathogenesis of AD and PD. However, the mechanisms underlying selective cholinergic and dopaminergic neurodegeneration in AD and PD are still unknown. We demonstrated that APPSWE mutation enhanced Aß generation and increased cell susceptibility to Aß oligomer in cholinergic SN56 cells, whereas SNCAA53T mutations promoted aggregates formation and potentiated mutant α-synuclein oligomer-induced cytotoxicity in MN9D cells. Furthermore, syndecan-3 (SDC3) and fibroblast growth factor receptor-like 1 (FGFRL1) genes were differentially expressed in SN56 and MN9D cells carrying APPSWE or SNCAA53T mutation. SDC3 and FGFRL1 proteins were preferentially expressed in the cholinergic nucleus and dopaminergic neurons of APPSWE and SNCAA53T mouse models, respectively. Finally, the knockdown of SDC3 and FGFRL1 attenuated oxidative stress-induced cell death in SN56-APPSWE and MN9D-SNCAA53T cells. The results demonstrate that SDC3 and FGFRL1 mediated the specific effects of APPSWE and SNCAA53T on cholinergic and dopaminergic neurodegeneration in AD and PD, respectively. Our study suggests that SDC3 and FGFRL1 could be potential targets to alleviate the selective neurodegeneration in AD and PD.

Spatial relationship between land urbanization and ecosystem health in the Yangtze River Basin, China.

Globally, land-based urbanization had far-reaching impacts on ecosystem health. Determining the spatial relationship between land urbanization and ecosystem health is important for sustainable socioeconomic development and ecological protection. However, existing studies lack research on these relationships in basin regions, which may limit the implementation of effective basin ecological management measures. Based on multi-source data, this study analyzed the spatiotemporal patterns and spatial correlations of land urbanization rate (LUR) and ecosystem health index (EHI) in the Yangtze River basin (YRB) with a series of spatial analysis methods. The results showed that EHI in the YRB decreased by 0.024 during 2000-2020, with a decreasing range of 3.133 %, while LUR increased by 0.216, with an increasing range of 54.135 %. LUR has a significant negative spatial correlation with EHI, with high EHI and high LUR (9.814% in 2020) and high EHI and low LUR (12.397% in 2020) being the main types of agglomeration. The global regression results showed that LUR significantly negatively affected EHI. At the local scale, the LUR positively affected the EHI in the mountainous region, while the opposite was confirmed in the plain region. This study can provide scientific reference for the development of sustainable urban land control measures and basin ecological management measures.

Clinical Features, Risk Factors, and Early Prognosis for Wallerian Degeneration in the Descending Pyramidal Tract after Acute Cerebral Infarction.

BACKGROUND: Wallerian degeneration(WD) occurs in the descending pyramidal tract(DPT) after cerebral infarction commonly, but studies of its degree evaluation, influencing factors and effects on nervous function are still limited. OBJECTIVES: The purpose of this study was to describe these findings and estimate their clinical significance. METHODS: In total, 133 patients confirmed acute cerebral infarction and restricted diffusion in the DPT of the cerebral peduncle by MRI scans. These cases were retrospectively reviewed. We describe their clinical characteristics and analyze influence factors of WD, including the timespan from symptom onset to MRI and TOAST classification. Their NIHSS scores at admission and first 7 days NIHSS improvement rate after admission were also analyzed. RESULTS: These patients were divided into three groups by timespan ≤7 days(n = 45),7-14 days(n = 70) and >14 days(n = 18). The mean WD degree (%)of these three groups was 44.41 ± 22.51,52.35 ± 22.61and 44.31 ± 19.35,respectively(p = 0.122).According to the TOAST classification, the mean WD degree(%) of the cardioembolism group(n = 28, 62.80 ± 25.12) was significantly different from both the large-artery atherosclerosis group(n = 73,45.08 ± 20.03,p = 0.000) and the small-vessel occlusion group(n = 23,39.68 ± 16.95,p = 0.000). The mean NIHSS score upon admission of the WD degree≤50% group(n = 82,8.17 ± 5.87) was different from that of the >50% group(n = 51,11.31 ± 7.00)(p = 0.006). However, the mean 7 days NIHSS improvement rate(%) of the WD degree≤50% group(n = 79,11.83 ± 23.76)and >50% group(n = 50,13.40 ± 27.88) was not significantly different(p = 0.733). CONCLUSIONS: Early WD in ischemic stroke patients has a correlation with serious baseline functional defects. Therefore, we should give close attention to imaging change, especially in those with cardioembolism .

Simultaneous Pulmonary Embolism and Ischemic Stroke in a Patient with Cor Biloculare after Glenn Anastomosis.

BACKGROUND: Cor biloculare, two-chambered heart due to the absence of atrial and ventricular septa, is a rare congenital heart anomaly. For Cor biloculare and other cardiac defects with single ventricle physiology, Glenn anastomosis has been developed as a palliative procedure. Thrombosis secondary to Glenn anastomosis in the patient with Cor biloculare could pose a serious threat to the survival, and has never been reported before. CASE REPORT: We report the case of a 27-year-old patient, with past history of Glenn anastomosis that was performed 7 years ago for the palliation of Cor biloculare. She presented with pulmonary embolism and ischemic stroke simultaneously at 7 days after Cesarean section. Due to her critical status, systemic anticoagulation with low-molecular-weight heparin was started immediately, followed by lifelong warfarin therapy. Pulmonary embolism regressed and neurological symptoms were considerably diminished after the anticoagulation treatment. CONCLUSION: This case illuminates the potential risk of thrombotic events in this patient cohort and demonstrates that anticoagulation therapy is an effective, secure, and appropriate for the management of this disease.

S100B promotes microglia M1 polarization and migration to aggravate cerebral ischemia.

AIM AND OBJECTIVE: S100B has been found abundantly expressed in microglia during cerebral ischemia. However, S100B effects on phenotype changes and migration of microglia are unclear. METHODS: Real-time PCR of S100B, M1 and M2 markers were tested to characterize phenotypic changes in microglia in mice middle cerebral artery occlusion (MCAO) model. Migration assay and additional mechanism studies were performed to elucidate the role of NF-κB in S100B-mediated microglia M1/M2 phenotype change and migration. Finally, S100B treatment on MCAO models was performed to show the in vivo evidence. RESULTS: S100B was identified as an induced gene with its pattern in accordance with M1 markers in mice MCAO model. That S100B was promoted by M1 stimuli whereas inhibited by M2 stimuli further confirmed S100B a M1 marker. Moreover, S100B promotes microglia M1 polarization with enhanced migration ability and inhibits M2 polarization. Additionally, NF-κB is essential in S100B control in microglia M1/M2 polarization and migration. Furthermore, S100B aggravated cerebral ischemia in murine MCAO model and exacerbated the microglia M1 polarization and migration. CONCLUSIONS: Our findings demonstrate that S100B promotes microglia M1 polarization to aggravate cerebral ischemia, and provide a better understanding on the therapeutic effects of S100B and/or its antagonist/neutralization antibody in stroke.

Molecular Mechanism Exploration of Ischemic Stroke by Integrating mRNA and miRNA Expression Profiles.

BACKGROUND: Stroke is one of the leading causes of death worldwide, and ischemic stroke accounts for about 80 percent of all cases. Ischemic stroke is usually caused by a blockage in an artery to the brain. However, its molecular mechanisms remain largely unclear. The integration of mRNA and miRNA expression patterns is an effective strategy to investigate the potential molecular mechanisms of ischemic stroke in posttranscriptional regulation level. METHODS: The mRNA and miRNA expression data were downloaded from the GEO database. The genes and miRNAs with fold change ≥ 1.5 and p-value ≤ 0.05 were considered differential expressions. GO and KEGG pathway annotations of differentially expressed genes were performed to investigate the potential biology function. The constructed mRNA-miRNA interaction networks were used to identify new genes and molecular mechanism of ischemic stroke. RESULTS: Three hundred thirty-eight DEGs (differentially expressed genes) in mRNA expression data were collected from blood samples of 23 patients with ischemic stroke and 23 vascular risk factor controls, and 8 miRNAs from peripheral blood cells of 48 patients with ischemic stroke and vascular risk factor controls. By analyzing the mRNA-miRNA regulation network, 6 miRNAs are responsible for the differential expression of 63 DEGs. Among these miRNAs, 4 screened miRNAs were shown to regulate oxidative stress, apoptosis, and thrombus formation of ischemic stroke in previous reports. In addition, the predicted target genes, such as BCL2A1 and TPM2, showed a crucial or potential role in the pathogenic mechanism of ischemic stroke. CONCLUSIONS: These results deciphered posttranscriptional regulation of the molecular mechanism of ischemic stroke and identified valuable genes in the development process of ischemic stroke.

Low T3 levels as a predictor marker predict the prognosis of patients with acute ischemic stroke.

BACKGROUND: Early and accurate prediction of outcome in acute stroke is important. The aim of this prospective study was to explore the correlation between serum triiodothyronine level and prognosis in acute ischemic stroke patients. METHODS: A prospective observational study which included 359 consecutive patients with acute ischemic stroke from December 2014 to November 2015 was interrogated. Serum triiodothyronine (T3) concentrations were measured on admission to understand their value in predicting functional outcome within 90 d using multivariable models adjusted for confounding factors. Receiver operating characteristic (ROC) curves were calculated to define the best cut-off value of triiodothyronine to predict outcome. The accuracy of the test was assessed measuring the area under the ROC curve (AUROC). RESULTS: Triiodothyronine was significantly decreased in patients with an unfavorable functional outcome as compared to patients with a favorable functional outcome within 90 d (p = 0.01). Binary logistic regression analyses revealed that lower triiodothyronine concentrations on admission were associated with a risk for poor outcomes (OR 0.05, 95% CI 0.01-0.25; p < 0.01). In addition, in ROC curve analysis, triiodothyronine may improve the National Institutes of Health Stroke Scale (NIHSS) score in predicting functional outcome. The combined model AUROC was 0.84 for 30 d and 0.91 for 90 d, which were both significantly higher than the AUROCs of original NIHSS (0.83 and 0.87), triiodothyronine (0.64 and 0.69) and age (0.57 and 0.68) (all p < 0.05). CONCLUSIONS: Low serum triiodothyronine levels can be a predictive marker of short-term outcome after ischemic stroke. A combined model (triiodothyronine, age and NIHSS score) can add significant additional predictive information to the clinical score of the NIHSS.

Tactile discrimination as a diagnostic indicator of cognitive decline in patients with mild cognitive impairment: A narrative review.

Background: Tactile discrimination, a cognitive task reliant on fingertip touch for stimulus discrimination, encompasses the somatosensory system and working memory, with its acuity diminishing with advancing age. Presently, the evaluation of cognitive capacity to differentiate between individuals with early Alzheimer's disease (AD) and typical older adults predominantly relies on visual or auditory tasks, yet the efficacy of discrimination remains constrained. Aims: To review the existing tactile cognitive tasks and explore the interaction between tactile perception and the pathological process of Alzheimer's disease. The tactile discrimination task may be used as a reference index of cognitive decline in patients with mild cognitive impairment and provide a new method for clinical evaluation. Methods: We searched four databases (Embase, PubMed, Web of Science and Google scholar). The reference coverage was from 1936 to 2023. The search terms included "Alzheimer disease" "mild cognitive impairment" "tactile" "tactile discrimination" "tactile test" and so on. Reviews and experimental reports in the field were examined and the effectiveness of different types of tactile tasks was compared. Main results: Individuals in the initial phases of Alzheimer's spectrum disease, specifically those in the stage of mild cognitive impairment (MCI), exhibit notable impairments in tasks involving tactile discrimination. These tasks possess certain merits, such as their quick and straightforward comparability, independence from educational background, and ability to circumvent the limitations associated with conventional cognitive assessment scales. Furthermore, tactile discrimination tasks offer enhanced accuracy compared to cognitive tasks that employ visual or auditory stimuli. Conclusions: Tactile discrimination has the potential to serve as an innovative reference indicator for the swift diagnosis of clinical MCI patients, thereby assisting in the screening process on a clinical scale.

A High-Tryptophan Diet Alleviated Cognitive Impairment and Neuroinflammation in APP/PS1 Mice through Activating Aryl Hydrocarbon Receptor via the Regulation of Gut Microbiota.

SCOPE: Recent studies have highlighted the vital role of gut microbiota in the pathogenesis of Alzheimer's disease (AD). However, the effect of the regulation of gut microbiota by dietary components on AD remains unknown. Thus, the study explored that a high-tryptophan (Trp) diet alleviates cognitive impairment by regulating microbiota. METHODS AND RESULTS: Male APP/PS1 mice are fed 0.5% Trp diet for 4 weeks, and then cognitive function, amyloid-ß (Aß) deposition, microglial activation, proinflammatory cytokines production, and gut microbiota are detected. Moreover, the level of aryl hydrocarbon receptor (AhR) and NF-κB pathway related protein are determined. The results show that high-Trp diet significantly alleviates cognitive impairment and Aß deposits. Moreover, high-Trp diet significantly inhibits activation of microglia, decreases the level of cluster of differentiation 11b (CD11b), and restrains the activation markers of microglia, such as cyclooxygenase-2 (Cox-2), interleukin (IL)-1ß, and IL-6. Notably, high-Trp diet significantly activates AhR, inhibits the phosphorylation of p65, and improves microbiota dysbiosis. CONCLUSIONS: These findings demonstrated that high-Trp diet exerts anti-inflammatory effects via upregulating AhR and suppressing NF-κB pathway, and its mechanisms may be mediated by regulating gut microbiota, suggesting that Trp diet may be a potential strategy for AD intervention.

Electroclinical characteristics of posterior lateral temporal epilepsy.

The current study aimed to investigate the electroclinical differences between mesial temporal lobe epilepsy (MTLE) and posterior lateral temporal lobe epilepsy (PLTLE). All patients had Engel class I outcomes after surgery for at least one year. In MTLE patients, the epileptogenic zone was inside the boundary of a standard temporal lobectomy, whereas in PLTLE, the epileptogenic zone was behind the boundary of a standard temporal lobectomy. Febrile convulsion, history of psychic aura, oroalimentary automatism, and diffuse interictal epileptiform discharges were more frequent in MTLE. Theta wave and increasing heart rate were more evident at the seizure onset in MTLE, whereas an ictal onset fast rhythm was more evident in PLTLE. Tonic head turning was more frequent in PLTLE. Distinguishing between MTLE and PLTLE was easier than distinguishing MTLE from lateral TLE (LTLE), which may be helpful in planning epilepsy surgery. Combinations of these manifestations and signs can provide vital clues to distinguish between MTLE and PLTLE.

Exploring the coupling and decoupling relationship of urbanization and carbon emissions in China.

Burgeoning urbanization is a defining challenge for global carbon emissions mitigation in the coming decades. In this context, achieving low-carbon urbanization remains an urgent issue that demands prompt solutions. The coupling and decoupling relationships between urbanization and carbon emissions play an important role in the coordination of urbanization development and carbon emissions reduction, which has rarely been explored in existing studies, especially in China at the county level. To address this gap, the coupling and decoupling relationship between the urbanization level (UL) and carbon emissions density (CED) was explored using an improved coupling degree model and the Tapio decoupling method in China at the county level from 2000 to 2020. The results showed that the UL and CED of China both exhibited increasing trends, and the spatial distribution was quite similar, with the UL increasing from 0.018 in 2000 to 0.028 in 2020 and the CED increasing from 95.163 ton/km2 in 2000 to 295.746 ton/km2 in 2020. The spatial distribution of hotspots in the UL change differed with time, whereas that in the CED change was relatively stable. However, both of them were concentrated in eastern China. The coupling degrees of the UL and CED in China were 0.348, 0.355, 0.369, 0.370, and 0.338 in 2000, 2005, 2010, 2015, and 2020, respectively, with the moderately unbalanced type (>35%) being dominant at the county level and mainly scattered in eastern China. The changes in the spatial distribution patterns of the 10 subcategories were quite limited, with the systematically balanced type being dominant (89%). The decoupling types of the UL and CED during 2000-2005, 2005-2010, and 2010-2015 were weak decoupling, while those in 2015-2020 were expansive negative decoupling. At the county level, the most significant transition occurred between expansive negative decoupling, strong decoupling, and strong negative decoupling. The proportion of strong decoupling type counties peaked in 2015-2020 (70.86%), whereas that of the strong negative decoupling type counties remained high (17.55%), scattering the country. These findings can advance policy enlightenment of low-carbon urbanization and green development for China against the backdrop of "30·60 dual carbon" goal.

Regional differences in spatial determinants of land urbanization in China.

China has entered a critical stage of urbanization transition but still faces unbalanced regional development and uncoordinated urban-rural integration. Studying the regional differences in spatial determinants of land urbanization (LU) is crucial to achieving coordinated regional development of urbanization. However, the spatial determinants of LU remain unclear, especially in terms of their regional differences. Therefore, this study introduced dynamic distribution and spatial analysis to measure regional differences in spatial determinants of LU in China. During 1990-2020, the imbalance of LU in China was constantly decreasing, and the differences in LU among different regions were also decreasing. LU in China had significant spatial dependence and spatial spillover effects, and the trend of group development was gradually becoming obvious. LU in eastern region was more affected by natural factors than in central and western regions, while central and western regions were more affected by socioeconomic factors than in eastern region. This study can provide a scientific reference for understanding the spatial disequilibrium of LU and promoting the regional implementation of LU coordinated development.

Identifying the driving forces of cultivated land fragmentation in China.

Cultivated land fragmentation (CLF) has severely affected China's agricultural production efficiency, large-scale operations, agricultural modernization, and food security. Exploring the spatiotemporal evolution patterns and driving forces of CLF is crucial for agricultural modernization. However, the driving forces of CLF in different agricultural regions in China still need to be clarified. In this study, CLF was measured in 2000, 2010, and 2020 based on remote sensing data with landscape pattern metrics, and the driving forces of spatial differentiation were detected based on a geographical detector model. The overall cultivated land area has slightly declined during the study period while the CLF has intensified. CLF showed significant spatial autocorrelation, with CLF increased-cultivated land decreased (2000 to 2010) and CLF decreased-cultivated land decreased (2010 to 2020). The contribution rate of land use intensity on CLF was the highest among all agricultural regions, excluding the Qinghai Tibet Plateau. In contrast, the contribution rates of other factors significantly varied across agricultural regions. These findings provide scientific support in formulating policies to conserve cultivated land for sustainable use of agricultural resources and CLF management in China.

Regional differences and driving forces of ecosystem health in Yangtze River Basin, China.

Ecosystem health in the Yangtze River basin (YRB) shows significant regional differences. Analysis of regional differences and drivers of ecosystem health in YRB is of practical significance for sustainable basin ecological management. However, existing studies lack research on regional differences and driving forces of ecosystem health, especially in big basin regions. Based on multi-source data, this study adopted spatial statistics and distribution dynamics models to quantitatively analyze the regional differences of ecosystem health in the YRB during 2000-2020 and employed the spatial panel model to reveal the driving forces of ecosystem health in the YRB. The ecosystem health index of the upper, middle, and lower reaches of YRB and the entire basin in 2020 was 0.753, 0.781, 0.637, and 0.742, respectively, while they all decreased during 2000-2020. Regional differences in YRB ecosystem health increased during 2000-2020. From the perspective of dynamic evolution, low-level and high-level ecosystem health units evolved to high-level, while medium-high-level ecosystem health units evolved to low-level. High-high (accounting for 30.372% in 2020) and low-low (accounting for 13.533% in 2020) were the main cluster types. Regression result showed that urbanization was the main reason for ecosystem health deterioration. The findings can provide enlightenment to further understand the regional differences of ecosystem health in YRB and provide theoretical reference for the coordinated management of ecosystem at macro-level and the differential regulation of local ecosystem at micro-level in the basin region.

A Chinese pedigree with Perry disease caused by the p.Y78H mutation in DCTN1: A 6-year clinical follow-up.

PURPOSE: Perry disease is a rare autosomal dominant neurodegenerative disorder with core features of parkinsonism, depression, apathy, weight loss, and central hyperventilation. To date, few cases of Perry disease have been reported worldwide, and they are all due to mutations in the DCTN1 gene. We report a case of a Chinese pedigree. METHODS: Clinical information was collected from a Chinese pedigree. Brain magnetic resonance imaging, pulmonary function tests, and arterial blood gas analysis were performed on both the proband and his youngest aunt. Genomic DNA from the proband's aunt was analyzed using whole-exome sequencing to detect genetic mutations. RESULTS: The family displayed an autosomal dominant mode of inheritance, and we identified a p.Y78H mutation in DCTN1. After 6 years of follow-up, the proband exhibited mood-related "on-off" phenomena, weight gain, and used a CPAP ventilator at night. The proband's aunt presented with weight loss and respiratory failure four years after disease onset. CONCLUSION: This study reports a Chinese family with Perry disease. The mutation of DCTN1 in this family is p.Y78H. We share the findings in this family, hoping to increase our understanding of Perry disease in clinical work. DATA AVAILABILITY STATEMENT: The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Evolution Characteristics and Formation Mechanism of Production-Living-Ecological Space in China: Perspective of Main Function Zones.

The main function zone (MFZ) is the major strategy of China's economic development and ecological environment protection. Clarifying the logical relationship between "MFZ strategy" and "territorial spatial layout" is vital to construct regional economic layout and territorial spatial supporting system of high-quality development. However, few studies have revealed the evolution process and formation mechanism of the production-living-ecological space (PLES) structure of China's MFZ over a long period of time. To bridge the gap, based on the land use dataset in China from 1980 to 2020, this study analyzed the evolution patterns of PLES in China's MFZs using multiple methods and measured the formation mechanism of PLES in different types of MFZs with the GeoDetector model. Results showed that the spatial structure of China's national territory has evolved drastically in the past 40 years, showing significant horizontal regional differentiation and vertical gradient differentiation. Ecological space has been continuously decreasing, while production space and living space have been continuously increasing, and the evolution of PLES varied significantly in different MFZs. During the study period, the gravity center of PLES in China all moved westward. The spatial distribution pattern of production space and living space was from northeast to southwest, and the ecological space was from east to west. The evolution of China's territorial spatial structure was subject to the combined effects of natural and socio-economic factors, exhibiting significant differences in different MFZs. Land use intensity had the most prominent influence on the formation of PLES, followed by elevation. The influences of different factors on PLES structure were strengthened mainly through two types of nonlinear enhancement and dual-factor enhancement. This study can provide scientific support for the optimal management and high-quality development of territorial space in China.

Spatial correlation among cultivated land intensive use and carbon emission efficiency: A case study in the Yellow River Basin, China.

Considering the current global goal of carbon neutrality, the relationship between cultivated land intensive use (CLIU) and carbon emission efficiency (CEE) should be explored to address the global climate crisis and move toward a low-carbon future. However, previous work in this has been conducted at provincial/regional scales and few have identified the spatial correlation between CLIU and CEE at the scale of large river basins. Therefore, this study explored the spatiotemporal characteristics of CLIU, cultivated land carbon emissions (CLCE), and CEE, as well as the spatial correlation between CLIU and CEE in the Yellow River Basin (YRB), China. A comprehensive evaluation model, the Intergovernmental Panel on Climate Change (IPCC) coefficient methodology, existing data envelopment analysis model, and bivariate spatial autocorrelation models were used to analyze statistical data from 2005 to 2017. We found that the overall CLIU and CLCE values in the YRB exhibited a continuous increase; the average carbon emission total efficiency and carbon emission scale efficiency first decreased and then increased, and the average carbon emission pure technical efficiency gradually decreased. Areas of high CLCE were concentrated in eastern areas of the YRB, whereas those of high CLIU, carbon emission total efficiency, carbon emission scale efficiency, and carbon emission pure technical efficiency predominantly appeared in the eastern areas, followed by central and western areas of the YRB. Spatial analysis revealed a significant spatial dependence of CLIU on CEE. From a global perspective, the spatial correlations between CLIU and CEE changed from positive to negative with time. Moreover, the aggregation degree between CLIU and CEE gradually decreases with time, while the dispersion degree increases with time, and the spatial correlation gradually weakens. The local spatial autocorrelation further demonstrates that the number of high-low and low-high clusters between CLIU and CEE gradually increases over time, while the number of high-high and low-low clusters gradually decreased over time. Collectively, these findings can help policymakers formulate feasible low-carbon and efficient CLIU policies to promote win-win cooperation among regions.

Spatio-Temporal Variation and Influencing Factors of the Coupling Coordination Degree of Production-Living-Ecological Space in China.

Territorial space is a multi-functional complex. The coordinated production-living-ecological space (PLES) effectively coordinates the man-land relationship, promotes regional sustainable development, and maximizes territorial space. How to build a high-quality national spatial layout and support system for development has become a hot topic of concern in all sectors of society. However, few studies have explored the coupling coordination considering the various production-living-ecological functions of land use type and its influencing factors of PLES at the county scale in China. To address the gap, based on the connotation of PLES theory, this study established a classification and evaluation system for PLES and analyzed the spatio-temporal characteristics, coupling coordination degree, spatial autocorrelation, and influencing factors of PLES in China from 2000 to 2020. The results are as follows: (1) The production space index and living space index in China showed a continuous increase tendency, while the ecological space index decreased continuously during the study period. The production space and living space were concentrated in the east of Hu Line, and the ecological space indexes in mountainous areas were significantly higher than those in plain areas during the study period. (2) The gravity centers of PLES all migrated to the west of China to different degrees during the study period. (3) From 2000 to 2020, the basically balanced category was the main coupling coordination type, and the number of seriously unbalanced categories accounted for the least. In the west of the Hu Line, the seriously unbalanced category was dominant, while in the east of the Hu Line were the moderately unbalanced categories and above. (4) During the study period, the low-low type was the main relationship type, widely distributed in western China, followed by the high-high type, mainly situated in the North China Plain, Yangtze River Delta, Pearl River Delta, Jianghan Plain, Chengdu Plain, Northeast China Plain, and some provincial capital cities. (5) Regression results showed that natural factors were the main reason restricting the coordinated development of PLES, and socioeconomic factors could effectively promote the coordinated development of PLES. Landscape pattern also significantly influenced the coordinated development of PLES, but varied greatly. The findings of this study can provide a scientific reference for the optimization of territorial space layout and the promotion of high-quality development of territorial space.

SCN1A-Related Epilepsy: Novel Mutations and Rare Phenotypes.

Objectives: To expand the genotypes and phenotypes of sodium voltage-gated channel alpha subunit 1 (SCN1A)-related epilepsy. Methods: We retrospectively collected the clinical and genetic information of 22 epilepsy patients (10 males, 12 females; mean: 9.2 ± 3.9 years; 3.9-20.3 years) carrying 22 variants of SCN1A. SCN1A mutations were identified by next-generation sequencing. Results: Twenty-two variants were identified, among which 12 have not yet been reported. The median age at seizure onset was 6 months. Sixteen patients were diagnosed with Dravet syndrome (DS), two with genetic epilepsy with febrile seizures plus [one evolved into benign epilepsy with centrotemporal spikes (BECTS)], one with focal epilepsy, one with atypical childhood epilepsy with centrotemporal spikes (ABECTS) and two with unclassified epilepsy. Fourteen patients showed a global developmental delay/intellectual disability (GDD/ID). Slow background activities were observed in one patient and epileptiform discharges were observed in 11 patients during the interictal phase. Significance: This study enriches the genotypes and phenotypes of SCN1A-related epilepsy. The clinical characteristics of patients with 12 previously unreported variants were described.

Probiotic Pediococcus pentosaceus ameliorates MPTP-induced oxidative stress via regulating the gut microbiota-gut-brain axis.

Recent evidence demonstrated that functional bacteria were involved in the regulation of Parkinson's disease (PD). However, the mechanism of probiotics in improving PD was unclear. Here the antioxidant effect and the mechanism of probiotics Pediococcus pentosaceus (PP) on PD were studied by regulating the gut-brain axis. In this study, male C57BL/6J mice were injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intraperitoneally to establish a PD model and were then treated with PP for 4 weeks. Subsequently, a series of neurobehavioral tests to evaluate the motor function of the mice was performed. Additionally, degeneration of dopaminergic neurons, accumulation of α-synuclein, the production of an oxidative stress response, and the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) pathway-related proteins were evaluated. Moreover, the gut microbial composition and the level of metabolite γ-aminobutyric acid (GABA) were assessed. The results showed that PP treatment could improve MPTP-induced motor deficits, the degeneration of dopaminergic neurons, and the accumulation of α-synuclein. Moreover, PP treatment significantly increased the levels of SOD1, Gpx1, and Nrf2, while it decreased the levels of Keap1 in the brain of MPTP-induced mice. Notably, PP treatment improved the gut microbial dysbiosis and increased the level of GABA in MPTP-induced mice. These findings indicated that PP might represent a promising candidate, due to the metabolite of GABA, that could be used for the treatment of PD.