OsAAP8 mutation leads to significant improvement in the nutritional quality and appearance of rice grains.

Members of the permease gene family are responsible for important biological functions in the growth and development of rice. Here, we show that OsAAP8 is a constitutive expression gene, and its translated protein is localized on the cell membrane. Mutation of the OsAAP8 can promote the expression of genes related to protein and amylopectin synthesis, and also promote the enlargement of protein bodies in its endosperm, leading to an increase in the protein, amylopectin, and total amino acid content of grains in OsAAP8 mutants. Seeds produced by the OsAAP8 mutant were larger, and the chalkiness traits of the OsAAP8 mutants were significantly reduced, thereby improving the nutritional quality and appearance of rice grains. The OsAAP8 protein is involved in the transport of various amino acids; OsAAP8 mutation significantly enhanced the root absorption of a range of amino acids and might affect the distribution of various amino acids. Therefore, OsAAP8 is an important quality trait gene with multiple biological functions, which provides important clues for the molecular design of breeding strategies for developing new high-quality varieties of rice. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01473-w.

A deep belief rule base-based fault diagnosis method for complex systems.

Complex systems are prone to faults due to their intricate structures, potentially impacting system stability. Therefore, fault diagnosis has become crucial for maintaining stable operation. In the field of complex systems, the combinatorial explosion problem in belief rule base (BRB) has attracted significant attention. The interdependence among system components leads to numerous variables and the need for rules, heightening model complexity. Regarding the combinatorial explosion problem, an improved belief rule network structure called deep BRB (DBRB) is proposed. First, the extreme gradient boosting (XGBoost) feature selection method is employed to choose the relatively important feature subset. Next, driven by the importance of features, different levels of features are input into the model, forming a complete and progressive network structure. Finally, the model undergoes the reasoning and optimization process. The effectiveness of the model is confirmed with a bearing fault dataset. After a comprehensive evaluation of multiple indicators, this method demonstrates a consistent improvement in classification performance as the depth increased. Moreover, compared to the traditional BRB model, this method notably reduces the number of parameters, improving its efficiency of processing complex data. In short, this method effectively tackles combinatorial explosion while ensuring model performance. The selection and assignment of feature subsets enhance the logic and readability of the model. Through the network structure, various fault features are captured well. This fault diagnosis method, rooted in the DBRB, offers a novel perspective on diagnosing complex system faults.

A complex system health state assessment method with reference value optimization for interpretable BRB.

Health condition assessment is the basis for formulating and optimizing maintenance strategies of complex systems, which is crucial for ensuring the safe and stable operation of these systems. In complex system health condition assessment, it is not only necessary for the model to handle various uncertainties to ensure the accuracy of assessment results, but also to have a transparent and reasonable assessment process and interpretable, traceable assessment results. belief rule base (BRB) has been widely used as an interpretable modeling method in health condition assessment. However, BRB-based models currently face two issues: (1) inaccuracies in expert-provided parameters that can affect the model's accuracy, and (2) after model optimization, interpretability may be reduced. Therefore, this paper proposes a new method for complex system health condition assessment called interpretable BRB with reference value optimization (I-BRB). Firstly, to address the issue of inaccurate reference values, a reference value optimization algorithm with interpretability constraints is designed, which optimizes the reference values without compromising expert knowledge. Secondly, the remaining parameters are optimized using the projection covariance matrix adaptation evolution strategy (P-CMA-ES) with interpretability constraints to improve the model's accuracy. Finally, a case study evaluating the bearing components of a flywheel system is conducted to validate the proposed method. Experimental results demonstrate that I-BRB achieves higher accuracy in health condition assessment.

Myo1d promotes alpha-synuclein transfer from brain microvascular endothelial cells to pericytes through tunneling nanotubes.

α-Synuclein preformed fibrils (α-syn PFF) in the blood can cross the blood-brain barrier and invade the central nervous system. Our previous study proved that α-syn PFF can be taken up by brain microvascular endothelial cells (BMVECs). Here, we found that α-syn PFF spread from BMVECs to pericytes with the highest transmission efficiency. We observed abundant tunneling nanotubes (TNTs) connecting BMVECs and pericytes, and α-syn PFF transmitted through these TNTs. Furthermore, α-syn PFF accumulation in BMVECs did not promote TNT formation, but activated the molecular motor Myo1d. Inhibition of Myo1d prevented α-syn PFF transfer from BMVECs to pericytes and decreased the colocalization of Myo1d and F-actin in BMVECs. In summary, we are the first to demonstrate that α-syn PFF spread from BMVECs to pericytes through a mechanism involving TNTs and myosin. Targeting Myo1d may be a promising approach to prevent α-syn spreading from the blood to the brain.

Cerebral Microvascular Injury Induced by Lag3-Dependent α-Synuclein Fibril Endocytosis Exacerbates Cognitive Impairment in a Mouse Model of α-Synucleinopathies.

The pathological accumulation of α-synuclein (α-Syn) and the transmission of misfolded α-Syn underlie α-synucleinopathies. Increased plasma α-Syn levels are associated with cognitive impairment in Parkinson's disease, multiple system atrophy, and dementia with Lewy bodies, but it is still unknown whether the cognitive deficits in α-synucleinopathies have a common vascular pathological origin. Here, it is reported that combined injection of α-Syn preformed fibrils (PFFs) in the unilateral substantia nigra pars compacta, hippocampus, and cerebral cortex results in impaired spatial learning and memory abilities at 6 months post-injection and that this cognitive decline is related to cerebral microvascular injury. Moreover, insoluble α-Syn inclusions are found to form in primary mouse brain microvascular endothelial cells (BMVECs) through lymphocyte-activation gene 3 (Lag3)-dependent α-Syn PFFs endocytosis, causing poly(ADP-ribose)-driven cell death and reducing the expression of tight junction proteins in BMVECs. Knockout of Lag3 in vitro prevents α-Syn PFFs from entering BMVECs, thereby reducing the abovementioned response induced by α-Syn PFFs. Deletion of endothelial cell-specific Lag3 in vivo reverses the negative effects of α-Syn PFFs on cerebral microvessels and cognitive function. In short, this study reveals the effectiveness of targeting Lag3 to block the spread of α-Syn fibrils to endothelial cells in order to improve cognition.

Dynamic evolution of urban infrastructure resilience and its spatial spillover effects: An empirical study from China.

Urban infrastructure resilience is an important perspective for measuring the development quality of resilient cities and an important way to measure the level of infrastructure development. This paper uses the kernel density estimation, exploratory spatial data analysis, and spatial econometric models to analyze the characteristics of dynamic evolution and the spillover effects of the infrastructure resilience levels in 283 prefecture-level and above cities in China from 2010 to 2019. Our results are as follows. (1) The overall level of urban infrastructure resilience increased. The eastern region had a higher level than the national average. In contrast, the central, western and north-eastern regions had a slightly lower level than the national average. (2) The areas with high and higher resilience levels were mostly cities with more developed economic and social conditions in Eastern China. The areas below moderate resilience levels show a certain degree of clustering and mainly include some cities in Central, Western, and Northeast China. (3) The national level of urban infrastructure resilience shows significant spatial clustering characteristics, and the spatial pattern from coastal to inland regions presents a hotspot-subhotspot-subcoldspot-coldspot distribution. (4) There is a differential spatial spillover effect of national urban infrastructure resilience, which is gradually strengthened under the role of the economy, financial development, population agglomeration and government funding and weakened under the role of urbanization, market consumption and infrastructure investment. By exploring the dynamic evolution of infrastructure resilience in cities at the prefecture level and above and its spatial spillover effects, we provide a scientific basis for avoiding the siphoning effect among cities, improving the level of infrastructure resilience, and guiding the construction and development of resilient cities.

Calcium/calmodulin-dependent serine protein kinase exacerbates mitochondrial calcium uniporter-related mitochondrial calcium overload by phosphorylating α-synuclein in Parkinson's disease.

α-Synuclein phosphorylation and mitochondrial calcium homeostasis are important mechanisms underlying mitochondrial dysfunction in Parkinson's disease, but the network regulating these mechanisms remains unclear. We identified the role of key phosphokinases and the pathological effects of α-synuclein phosphorylation on mitochondrial calcium influx and mitochondrial function in Parkinson's disease. The function of the key phosphokinase, calcium/calmodulin-dependent serine protein kinase, was investigated through loss- and gain-of-function experiments using a cell model of Parkinson's disease. The regulation of mitochondrial calcium uniporter-mediated mitochondrial calcium influx by calcium/calmodulin-dependent serine protein kinase was explored using a cellular model of Parkinson's disease. Coimmunoprecipitation experiments and α-synuclein mutation were used to explore the mechanism through which calcium/calmodulin-dependent serine protein kinase regulates mitochondrial calcium uniporter-mediated mitochondrial calcium influx and exacerbates mitochondrial damage in Parkinson's disease. Here, we show the pathogenic role of calcium/calmodulin-dependent serine protein kinase in Parkinson's disease progression. Calcium/calmodulin-dependent serine protein kinase phosphorylated α-synuclein to activate mitochondrial calcium uniporter and thus increase mitochondrial calcium influx, and these effects were blocked by α-synuclein S129A mutant expression. Furthermore, the calcium/calmodulin-dependent serine protein kinase inhibitor CASK-IN-1 exerted neuroprotective effects in Parkinson's disease. Collectively, our results suggest that calcium/calmodulin-dependent serine protein kinase phosphorylates α-synuclein to activate the mitochondrial calcium uniporter and thereby causes mitochondrial calcium overload and mitochondrial damage in Parkinson's disease. We elucidated a new role of calcium/calmodulin-dependent serine protein kinase in Parkinson's disease and revealed the potential therapeutic value of targeting calcium/calmodulin-dependent serine protein kinase in Parkinson's disease treatment.

Endothelial LRP1-ICD Accelerates Cognition-Associated Alpha-Synuclein Pathology and Neurodegeneration through PARP1 Activation in a Mouse Model of Parkinson's Disease.

Parkinson's disease (PD) is characterized by progressive loss of dopaminergic neurons and accumulation of misfolded alpha-synuclein (αSyn) into Lewy bodies. In addition to motor impairment, PD commonly presents with cognitive impairment, a non-motor symptom with poor outcome. Cortical αSyn pathology correlates closely with vascular risk factors and vascular degeneration in cognitive impairment. However, how the brain microvasculature regulates αSyn pathology and neurodegeneration remains unclear. Here, we constructed a rapidly progressive PD model by injecting alpha-synuclein preformed fibrils (αSyn PFFs) into the cerebral cortex and striatum. Brain capillaries in mice with cognitive impairment showed a reduction in diameter and length after 6 months, along with string vessel formation. The intracellular domain of low-density lipoprotein receptor-related protein-1 (LRP1-ICD) was upregulated in brain microvascular endothelium. LRP1-ICD promoted αSyn PFF uptake and exacerbated endothelial damage and neuronal apoptosis. Then, we overexpressed LRP1-ICD in brain capillaries using an adeno-associated virus carrying an endothelial-specific promoter. Endothelial LRP1-ICD worsened αSyn PFF-induced vascular damage, αSyn pathology, or neuron death in the cortex and hippocampus, resulting in severe motor and cognitive impairment. LRP1-ICD increased the synthesis of poly(adenosine 5'-diphosphate-ribose) (PAR) in the presence of αSyn PFFs. Inhibition of PAR polymerase 1 (PARP1) prevented vascular-derived injury, as did loss of PARP1 in the endothelium, which was further implicated in endothelial cell proliferation and inflammation. Together, we demonstrate a novel vascular mechanism of cognitive impairment in PD. These findings support a role for endothelial LRP1-ICD/PARP1 in αSyn pathology and neurodegeneration, and provide evidence for vascular protection strategies in PD therapy.

NRBF2 regulates the chemoresistance of small cell lung cancer by interacting with the P62 protein in the autophagy process.

Reversing chemotherapy resistance in small cell lung cancer (SCLC) is crucial to improve patient prognosis. The present study aims to investigate the underlying mechanisms in SCLC chemoresistance. We see that nuclear receptor binding factor 2 (NRBF2) is a poor prognostic factor in SCLC. The effects of NRBF2 on chemoresistance were determined in SCLC. The underlying molecular mechanisms of NRBF2 in the autophagy process in SCLC were examined. NRBF2 positively regulated autophagy, leading to drug resistance in SCLC. The MIT domain of NRBF2 directly interacted with the PB1 domain of P62. This interaction increased autophagic P62 body formation, revealing the regulatory role of NRBF2 in autophagy. Notably, NRBF2 was directly modulated by the transcription factor XRCC6. The MIT domain of NRBF2 interacts with the PB1 domain of P62 to regulate the autophagy process, resulting in SCLC chemoresistance. NRBF2 is likely a useful chemotherapy response marker and therapeutic target in SCLC.

TGR5 Agonist INT-777 Alleviates Inflammatory Neurodegeneration in Parkinson's Disease Mouse Model by Modulating Mitochondrial Dynamics in Microglia.

Parkinson's disease (PD) is one of the most common chronic progressive neurodegenerative diseases that affects both motor and non-motor functions. Bile acids modulate the immune system by targeting brain receptors. INT-777, a 6α-ethyl-23(S)-methyl derivative of cholic acid (S-EMCA), acts as an agonist for Takeda G protein-coupled receptor-5 (TGR5) and has neuroprotective properties. However, the effects of INT-777 on PD have not yet been investigated. In a subchronic PD model, mice treated with 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) developed motor deficits and cognitive impairment that were ameliorated after intranasal administration of INT-777. INT-777 prevented MPTP-induced neurodegeneration and microglia activation in the substantia nigra pars compacta, hippocampus, and cortical layer V. Based on bioinformatics and wet lab data, INT-777 inhibited microglia activation by suppressing the release of tumor necrosis factor alpha (TNF-α) in the hippocampus, along with secondary chemokines (C-C motif ligand 3 (CCL3) and CCL6) in these three brain regions. INT-777 inhibited TNF-α production by repairing mitochondrial damage, which was associated with nuclear factor-erythroid 2-related factor-2 (NRF2) activation and p62/LC3B-mediated autophagy. INT-777 reversed the downregulation of heme oxygenase-1 (HO1), NAD(P)H quinone oxidoreductase-1 (NQO1) and accumulation of p62 in microglia treated with 1-methyl-4-phenylpyridinium (MPP+). However, TGR5 knockdown in microglia abolished INT-777's inhibition of TNF-α release, resulting in neuronal death. Therefore, PD cognitive impairment is associated with hippocampal TNF-α elevation as a result of mitochondrial damage in microglia. Our data reveal the potential role of TGR5 in modulating inflammation-mediated neurodegeneration in PD, and provides new insights for bile acid metabolites as promising disease-modifying drugs for PD.

Global research trends in hyperuricemia: a bibliometric and visualized study.

OBJECTIVES: The global trend of research on hyperuricaemia (HUA) has not been well studied. Therefore, this study aimed to investigate the trend of research on HUA and compare the findings in publications from different countries, institutions, journals, and authors, to predict the research hotspots. METHODS: Publications related to HUA were searched using the Science Citation Index-Expanded Web of Science. The data were analysed by using the bibliometric methodology. Additionally, a graphical mapping was generated by using the VOS viewer software to carry out a co-occurrence analysis and to investigate the trend of publications in this field. RESULTS: A total of 6313 articles were included. The number of publications was increasing globally yearly. USA was the leading country in global research in this field, with the largest number of publications and citations as well as the highest H-index (H-index reflects both the number of publications and the number of citations per publication). PLOS One published the largest number of publications related to HUA. JOHNSON RJ T has published the largest number of papers in this field. Published studies could be classified into six clusters: 'Pathophysiology', 'HUA and metabolic syndrome', 'HUA and cardiovascular disease', 'HUA and gout', 'HUA and nephropathy', and 'Genome-wide research'. 'Pathophysiology', 'HUA and cardiovascular disease', 'HUA and gout', and 'Genome-wide research' were predicted as the next hot topics in HUA research. CONCLUSIONS: USA was the leading country in global research in this field. It is expected that an increasing research output will continue to be observed in the near future. 'Pathophysiology', 'HUA and cardiovascular disease', 'HUA and gout', and 'Genome-wide research' may be the next hotspots and hence need more attention in the future.

LncRNAs as a new regulator of chronic musculoskeletal disorder.

OBJECTIVES: In recent years, long non-coding RNAs (lncRNAs) have been found to play a role in the occurrence, progression and prognosis of chronic musculoskeletal disorders. DESIGN AND METHODS: Literature exploring on PubMed was conducted using the combination of keywords 'LncRNA' and each of the following: 'osteoarthritis', 'rheumatoid arthritis', 'osteoporosis', 'osteogenesis', 'osteoclastogenesis', 'gout arthritis', 'Kashin-Beck disease', 'ankylosing spondylitis', 'cervical spondylotic myelopathy', 'intervertebral disc degeneration', 'human muscle disease' and 'muscle hypertrophy and atrophy'. For each disorder, we focused on the publications in the last five years (5/1/2016-2021/5/1, except for Kashin-Beck disease). Finally, we excluded publications that had been reported in reviews of various musculoskeletal disorders during the last three years. Here, we summarized the progress of research on the role of lncRNA in multiple pathological processes during musculoskeletal disorders. RESULTS: LncRNAs play a crucial role in regulating downstream gene expression and maintaining function and homeostasis of cells, especially in chondrocytes, synovial cells, osteoblasts, osteoclasts and skeletal muscle cells. CONCLUSIONS: Understanding the mechanisms of lncRNAs in musculoskeletal disorders may provide promising strategies for clinical practice.

Targeted cell therapy for partial-thickness cartilage defects using membrane modified mesenchymal stem cells by transglutaminase 2.

Unlike full-thickness cartilage defects (FCD), partial-thickness cartilage defects (PCD) may still have residual healthy cartilage tissue, and therefore, the conventional clinical treatments such as microfracture and autologous chondrocyte implantation (ACI) are so traumatic that they may not be the suitable therapies for PCD. Although intra-articular injection of mesenchymal stem cells (MSCs) is a minimally invasive treatment, its therapeutic efficacy is markedly limited due to anoikis caused by failure of cell colonization in the injured area. By modifying a functional polypeptide on the MSC plasma membrane and exploiting the high expression of transglutaminase 2 (TGase2) in the regions of injured cartilage, we achieved targeted recognition and capture of modified MSCs by injured articular chondrocytes (ACs). In the in vitro co-culture model, MSCs improved the function of injured ACs and enhanced the chondrogenic differentiation potential of MSCs. Results of in vitro study also revealed that the activation of the AKT/mTOR signaling pathway may play an important role in the treatment of injured ACs by MSCs. Further, membrane-modified MSCs exhibited a better therapeutic effect than wide-type MSCs in a rabbit model of PCD. Thus, this unique cell membrane modification strategy provides a new cell-based therapeutic approach for the early treatment of articular cartilage defects and other joint diseases.

Serum Folate, Vitamin B12 Levels, and Systemic Immune-Inflammation Index Correlate With Motor Performance in Parkinson's Disease: A Cross-Sectional Study.

This study aimed to investigate the influence of serum folate, vitamin B12 (VitB12) levels, and inflammation-based scores on the motor performance status in Parkinson's disease (PD). We retrospectively collected data from 148 consecutive patients with idiopathic PD first admitted to our hospital. We measured whole blood count, albumin, lactate dehydrogenase, C-reactive protein, folate, and VitB12 levels and calculated the inflammation-based scores. The following scales were applied to assess the motor performance status: activity of daily living scale (ADL, the Barthel Index), the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III), and Hoehn-Yahr (H-Y) classification. The geometric mean of folate and VitB12 levels were 11.87 (ng/ml) and 330.52 (pmol/L), respectively. Folate deficiency (serum level < 4.0 ng/ml) and VitB12 deficiency (serum level < 133 pg/ml) were present in 0.7 and 5.4% of the patients, respectively. The mean prognostic nutritional index (PNI) and systemic immune-inflammation index (SII) were 47.78 ± 4.42 and 470.81 ± 254.05, respectively. The multivariate analyses showed that serum VitB12 level (P = 0.002) and SII (P = 0.005) were significant factors for ADL score; serum folate (P = 0.027) and VitB12 (P = 0.037) levels for UPDRS-III score; and serum folate (P = 0.066) and VitB12 (P = 0.017) levels for H-Y classification. The elevated folate level did correlate with greater decline in UPDRS-III score (P = 0.023) and H-Y classification (P = 0.003), whereas there was an obvious increase in ADL score (P = 0.048). SII was negatively associated (P < 0.001) with the ADL score. The three-dimensional drawing, combined with the effect of folate and VitB12 levels, showed that the lowest level of folate was associated with the lowest ADL score and the highest UPDRS-III score and H-Y classification. This study indicates that serum folate, VitB12 levels, and SII are significant factors influencing the motor performance status in patients with PD. SII is negatively associated with ADL. Elevated serum folate level correlates with mild motor impairment in patients with PD.

[Molecular mechanism of Spatholobi Caulis in treatment of lung cancer based on network pharmacology and molecular docking].

In this paper, the molecular mechanism of Spatholobi Caulis in the treatment of non-small cell lung cancer(NSCLC) was studied through network pharmacology and molecular docking analysis. With traditional Chinese medicine(TCM) Spatholobi Caulis as the study object, active ingredients of Spatholobi Caulis and corresponding potential drug targets were obtained from Traditio-nal Chinese Medicine Pharmacology Platform(TCMSP) database; GeneCards database was used to collect cancer-related genes; Cytoscape software was used to build Spatholobi Caulis active ingredient-target-pathway relationship network. DAVID database was used for GO and KEGG enrichment analysis of targets, KEGG signaling pathway was visualized, and compounds were screened out for molecular docking. Finally, in vitro experiments on human lung cancer cells, A549 treated with luteolin and licochalcone A were used to preliminarily verify the core targets and pathways, cell proliferation was detected by CCK-8 method, and expressions of caspase-3 and Bax protein were detected by Western blot. A total of 23 active components and 170 potential drug targets were selected from Spatholobi Caulis, involving 127 pathways in total. Molecular docking results showed that licochalcone A,(Z)-3-(4-hydroxy-3-methoxyphenyl)-N-[2-(4-hydroxy-phenyl) ethyl] acrylamide, consumeclose grain successfully docked with the key target EGFR, and binding energy of the three compounds was less than-5 kcal·mol~(-1). CCK-8 results showed that luteolin, licochalcone A, and Spatholobi Caulis extract had the inhibitory effect on human lung cancer A549 cells. Western blot showed that luteolin, licochalcone A and Spatholobi Caulis extract could induce cell apoptosis by increasing the expressions of pro-apoptotic factors caspase-3 and Bax. In this study, the anti-lung cancer effect of Spatholobi Caulis was studied through network pharmacology and molecular docking, in order to provide ideas for the molecular mechanism of Spatholobi Caulis in the treatment of lung cancer.

Global Research Trends in Shock Wave for Therapy from 1990 to 2019: A Bibliometric and Visualized Study.

OBJECTIVE: The publications of application and development of shock wave therapy showed consistent growth. The aim of this study was to investigate the global status and trends in the shock wave therapy field. METHODS: Publications about shock wave therapy from 1990 to 2019 were collected from the Web of Science database. The data were studied and indexed by using bibliometric methodology. For a visualized study, VOSviewer software was used to conduct bibliographic coupling analysis, coauthorship analysis, cocitation analysis, and co-occurrence analysis and to analyze the publication trends in shock wave therapy. RESULTS: A total of 3,274 articles were included. The number of publications was increasing per year globally. The USA made the largest contributions to the global research with the most citations (the highest h-index). The Journal of Urology had the highest publication number. The University of California System was the most contributive institution. Studies could be divided into seven clusters: urology, hepatology, cardiology, orthopedics, mechanism research of shock wave therapy, andrology, and principle of shock wave therapy. Orthopedics, andrology, and mechanism research of shock wave therapy could be the next hot topics in this field. CONCLUSIONS: Base on the trends, shock wave therapy is the theme of a globally active research field which keeps developing and extends from bench to bedside.

Identifying Parkinson's disease with mild cognitive impairment by using combined MR imaging and electroencephalogram.

OBJECTIVES: To analyse the changes of quantitative electroencephalogram (qEEG) and cortex structural magnetic resonance (MR) imaging in Parkinson's disease with mild cognitive impairment (PD-MCI) and to explore the "composite marker"-based machine learning model in identifying PD-MCI. METHODS: Retrospective analysis of patients with PD identified 36 PD-MCI and 35 PD with normal cognition (PD-NC). QEEG features of power spectrum and structural MR features of cortex based on surface-based morphometry (SBM) were extracted. Support vector machine (SVM) was established using combined features of structural MR and qEEG to identify PD-MCI. Feature importance evaluation algorithm of mean impact value (MIV) was established to sort the vital characteristics of qEEG and structural MR. RESULTS: Compared with PD-NC, PD-MCI showed a statistically significant difference in 5 leads and waves of qEEG and 7 cortical region features of structural MR. The SVM model based on these qEEG and structural MR features yielded an accuracy of 0.80 in the training set and had a high prediction accuracy of 0.80 in the test set (sensitivity was 0.78, specificity was 0.83, area under the receiver operating characteristic curve was 0.77), which was higher than the model built by the feature separately. QEEG features of theta wave in C3 had a marked impact on the model for classification according to the MIV algorithm. CONCLUSIONS: PD-MCI is characterized by widespread structural and EEG abnormality. "Composite markers" could be valuable for the individualized diagnosis of PD-MCI by machine learning. KEY POINTS: • Explore the brain abnormalities in Parkinson's disease with mild cognitive impairment by using the quantitative electroencephalogram and cortex structural MR simultaneously. • Multimodal features based support vector machine for identifying Parkinson's disease with mild cognitive impairment has an acceptable performance. • Theta wave in C3 is the most influential feature of qEEG and cortex structure MR imaging in identifying Parkinson's disease with mild cognitive impairment using support vector machine.

Non-pharmacological treatment for Parkinson disease patients with depression: a meta-analysis of repetitive transcranial magnetic stimulation and cognitive-behavioral treatment.

Background: Nowadays, antidepressants still are the mainstay of treatment for depression in Parkinson's disease (PD) but some recent studies report that medication might aggravate motor symptoms in PD patients. This meta-analysis aims to assess the effect of non-pharmacological treatments for depression in patients with PD.Materials and Methods: Only randomized controlled trials (RCTs) were included. The participants were PD patients with comorbid depression (dPD). The interventions had the equivalent effect of non-pharmacological treatments alone compared with control(s). Scores of depression scale were selected as the primary outcome, while scores of Unified Parkinson's Disease Rating Scale part III and the incidence of side effects were the secondary outcome. The statistics were pooled and presented as weighted mean differences (WMDs), standardized mean differences (SMDs), or risk ratios (RRs) with their 95% confidence intervals (CIs).Results: Fifteen articles were eventually included; twelve studies reported on repetitive transcranial magnetic stimulation (rTMS) and three used cognitive behavioral therapy (CBT). Other interventions failed to have qualified studies. Our data indicated that both rTMS and CBT could significantly improve depression scores in a short term (SMD = -0.621, 95% CI [-0.964, -0.278]; SMD = -1.148, 95% CI [-1.498, -0.798], respectively). In addition, rTMS could alleviate motor symptom (WMD = -2.617, 95% CI [-4.183, -1.051]) and was relatively safe (RR = 1.054, 95% CI [0.698, 1.592]).Conclusion: Our data suggest that rTMS can safely alleviate depression and motor symptoms in dPD at least for a short period. Moreover, compared with clinical monitoring, CBT can improve depressive symptoms.

Comparison of Chondrocytes in Knee Osteoarthritis and Regulation by Scaffold Pore Size and Stiffness.

In knee osteoarthritis (OA), there is more pronounced cartilage damage in the medial compartment ("lesion zone") than the lateral compartment ("remote zone"). This study fills a gap in the literature by conducting a systematic comparison of cartilage and chondrocyte characteristics from these two zones. It also investigates whether chondrocytes from the different zones respond distinctly to changes in the physical and mechanical microenvironment using three-dimensional porous scaffolds by changing stiffness and pore size. Cartilage was harvested from patients with end-stage varus knee OA. Cartilage from the lesion and remote zones were compared through histological and biomechanical assessments, and through proteomic and gene transcription analyses of chondrocytes. Gelatin scaffolds with varied pore sizes and stiffness were used to investigate in vitro microenvironmental regulation of chondrocytes from the two zones. Cartilage from the lesion and remote zones differed significantly (p < 0.05) in histological and biomechanical characteristics, as well as phenotype, protein, and gene expression of chondrocytes. Chondrocytes from both zones were sensitive to changes in the structural and mechanical properties of gelatin scaffolds. Of interest, although all chondrocytes better retained chondrocyte phenotype in stiffer scaffolds, those from the lesion and remote zones, respectively, preferred scaffolds with larger and smaller pores. Distinct variations exist in cartilage and chondrocyte characteristics in the lesion and remote zones of knee OA. Cells in these two zones respond differently to variations in the physical and mechanical microenvironment. Understanding and manipulating these differences will facilitate the development of more efficient and precise diagnostic and therapeutic approaches for knee OA.