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Parkinson’s Disease (PD) is the second most common neurodegenerative disease world-wide. Mutations in the multidomain protein Leucine Rich Repeat Kinase 2 (LRRK2) are the most frequent cause of hereditary PD. Furthermore, recent data suggest that independent of mutations, increased kinase activity of LRRK2 plays an essential role in PD pathogenesis. Isolated mitochondria of tissue samples from PD patients carrying LRRK2 mutations display a significant impairment of mitochondrial function. However, due to the complexity of the mitochondrial signaling network, the role of LRRK2 in mitochondrial metabolism is still not well understood. Previously we have shown that D. discoideum Roco4 is a suitable model to study the activation mechanism of LRRK2 in vivo. To get more insight in the LRRK2 pathways regulating mitochondrial activity we used this Roco4 model system in combination with murine RAW macrophages. Here we show that both Dictyostelium roco4 knockout and cells expressing PD-mutants show behavioral and developmental phenotypes that are characteristic for mitochondrial impairment. Mitochondrial activity measured by Seahorse technology revealed that the basal respiration of D. discoideum roco4- cells is significantly increased compared to the WT strain, while the basal and maximal respiration values of cells overexpressing Roco4 are reduced compared to the WT strain. Consistently, LRRK2 KO RAW 264.7 cells exhibit higher maximal mitochondrial respiration activity compared to the LRRK2 parental RAW264.7 cells. Measurement on isolated mitochondria from LRRK2 KO and parental RAW 264.7 cells revealed no difference in activity compared to the parental cells. Furthermore, neither D. discoideum roco4- nor LRRK2 KO RAW 264.7 showed a difference in either the number or the morphology of mitochondria compared to their respective parental strains. This suggests that the observed effects on the mitochondrial respiratory in cells are indirect and that LRRK2/Roco proteins most likely require other cytosolic cofactors to elicit mitochondrial effects.

Yuluo Rong,* Jiaxing Wang,* Tao Sui, Wei Liu, Yongjun Luo, Weihua CaiDepartment of Orthopaedics, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, People’s Republic of China*These authors contributed equally to this workObjective: To report a rare case of cervical intradural disc herniation (IDH) with Brown-Séquard syndrome and to review the related literature.Methods: Pathogenesis, preoperative diagnosis, and the surgical technique are discussed, and previous literature reports are reviewed.Results: A 44-year-old woman complained of weakness of the left upper and lower extremities and paresthesias in the right limbs after a bicycle ride 3 days earlier. She had a history of neck pain for 2 years prior. CT showed obvious ossification of the posterior longitudinal ligament (OPLL), and MRI revealed C3-7 disc herniations, with a positive “halo sign” around the herniated C4/5. We performed emergency decompression through anterior cervical corpectomy, and vertebrotomy decompression and fusion. At review 3 months after surgery, the patient’s neck pain was markedly relieved, and motor strength in the limbs had improved. At 1 year after surgery, she had recovered completely.Conclusion: Cervical IDH is a rare condition that may be related to the traumatic inflammatory response and OPLL. Relatively rare imaging features such as the hawk-beak sign, halo sign, Y sign, and epidural gas sign could help in preoperative diagnosis. Prompt anterior cervical decompression is the preferred treatment for this condition.Keywords: cervical intradural disc herniation, Brown-Séquard syndrome, ossification of posterior longitudinal ligament, cerebrospinal fluid leakage, surgical treatment

In combination with studies of post-mortem Parkinson's disease (PD) brains, pharmacological and genetic models of PD have suggested that two fundamental interacting cellular processes are impaired – proteostasis and mitochondrial respiration. We have re-examined the role of mitochondrial dysfunction in lymphoblasts isolated from individuals with idiopathic PD and an age-matched control group. As previously reported for various PD cell types, the production of reactive oxygen species (ROS) by PD lymphoblasts was significantly elevated. However, this was not due to an impairment of mitochondrial respiration, as is often assumed. Instead, basal mitochondrial respiration and ATP synthesis are dramatically elevated in PD lymphoblasts. The mitochondrial mass, genome copy number and membrane potential were unaltered, but the expression of indicative respiratory complex proteins was also elevated. This explains the increased oxygen consumption rates by each of the respiratory complexes in experimentally uncoupled mitochondria of iPD cells. However, it was not attributable to increased activity of the stress- and energy-sensing protein kinase AMPK, a regulator of mitochondrial biogenesis and activity. The respiratory differences between iPD and control cells were sufficiently dramatic as to provide a potentially sensitive and reliable biomarker of the disease state, unaffected by disease duration (time since diagnosis) or clinical severity. Lymphoblasts from control and PD individuals thus occupy two distinct, quasi-stable steady states; a ‘normal’ and a ‘hyperactive’ state characterized by two different metabolic rates. The apparent stability of the ‘hyperactive’ state in patient-derived lymphoblasts in the face of patient ageing, ongoing disease and mounting disease severity suggests an early, permanent switch to an alternative metabolic steady state. With its associated, elevated ROS production, the ‘hyperactive’ state might not cause pathology to cells that are rapidly turned over, but brain cells might accumulate long-term damage leading ultimately to neurodegeneration and the loss of mitochondrial function observed post-mortem. Whether the ‘hyperactive’ state in lymphoblasts is a biomarker specifically of PD or more generally of neurodegenerative disease remains to be determined.

The fragile X premutation (PM) allele contains a CGG expansion of 55–200 repeats in the FMR1 gene’s promoter. Male PM carriers have an elevated risk of developing neurological and psychiatric changes, including an approximately 50% risk of the fragile X-associated tremor/ataxia syndrome (FXTAS). The aim of this study was to assess the relationships of regional white matter hyperintensities (wmhs) semi-quantitative scores, clinical status, motor (UPDRS, ICARS, Tremor) scales, and cognitive impairments, with FMR1-specific genetic changes, in a sample of 32 unselected male PM carriers aged 39–81 years. Half of these individuals were affected with FXTAS, while the non-FXTAS group comprised subcategories of non-affected individuals and individuals affected with non-syndromic changes. The dynamics of pathological processes at the cellular level relevant to the clinical status of PM carriers was investigated using the enzyme AMP-activated protein kinase (AMPK), which is a highly sensitive cellular stress-sensing alarm protein. This enzyme, as well as genetic markers – CGG repeat number and the levels of the FMR1 mRNA – were assessed in blood lymphoblasts. The results showed that the repeat distribution for FXTAS individuals peaked at 85–90 CGGs; non-FXTAS carriers were distributed within the lowest end of the PM repeat range, and non-syndromic carriers assumed an intermediate position. The size of the CGG expansion was significantly correlated, across all three categories, with infratentorial and total wmhs and with all motor scores, and the FMR1 mRNA levels with all the wmh scores, whilst AMPK activity showed considerable elevation in the non-FXTAS combined group, decreasing in the FXTAS group, proportionally to increasing severity of the wmhs and tremor/ataxia. We conclude that the size of the CGG expansion relates to the risk for FXTAS, to severity of infratentorial wmhs lesions, and to all three motor scale scores. FMR1 mRNA shows a strong association with the extent of wmhs, which is the most sensitive marker of the pathological process. However, the AMPK activity findings – suggestive of a role of this enzyme in the risk of FXTAS – need to be verified and expanded in future studies using larger samples and longitudinal assessment.

The fragile X premutation (PM) allele contains a CGG expansion of 55-200 repeats in the FMR1 gene's promoter. Male PM carriers have an elevated risk of developing neurological and psychiatric changes, including an approximately 50% risk of the fragile X-associated tremor/ataxia syndrome (FXTAS). The aim of this study was to assess the relationships of regional white matter hyperintensities (wmhs) semi-quantitative scores, clinical status, motor (UPDRS, ICARS, Tremor) scales, and cognitive impairments, with FMR1-specific genetic changes, in a sample of 32 unselected male PM carriers aged 39-81 years. Half of these individuals were affected with FXTAS, while the non-FXTAS group comprised subcategories of non-affected individuals and individuals affected with non-syndromic changes. The dynamics of pathological processes at the cellular level relevant to the clinical status of PM carriers was investigated using the enzyme AMP-activated protein kinase (AMPK), which is a highly sensitive cellular stress-sensing alarm protein. This enzyme, as well as genetic markers - CGG repeat number and the levels of the FMR1 mRNA - were assessed in blood lymphoblasts. The results showed that the repeat distribution for FXTAS individuals peaked at 85-90 CGGs; non-FXTAS carriers were distributed within the lowest end of the PM repeat range, and non-syndromic carriers assumed an intermediate position. The size of the CGG expansion was significantly correlated, across all three categories, with infratentorial and total wmhs and with all motor scores, and the FMR1 mRNA levels with all the wmh scores, whilst AMPK activity showed considerable elevation in the non-FXTAS combined group, decreasing in the FXTAS group, proportionally to increasing severity of the wmhs and tremor/ataxia. We conclude that the size of the CGG expansion relates to the risk for FXTAS, to severity of infratentorial wmhs lesions, and to all three motor scale scores. FMR1 mRNA shows a strong association with the extent of wmhs, which is the most sensitive marker of the pathological process. However, the AMPK activity findings - suggestive of a role of this enzyme in the risk of FXTAS - need to be verified and expanded in future studies using larger samples and longitudinal assessment.

Abstract Two major earthquakes of Mw7.8 and Mw7.5 ruptured the Southern East Anatolian Fault (SEAF) and the Savrun‐Çardak‐Sürgü fault (SCSF), devastating southeast Türkiye and northwest Syria on 6 February 2023. We adopt innovative nonlinear and linear approaches to analyze the coseismic ground displacements and estimate the complex slip geometry. Unlike conventional analytical solutions that simplify crust heterogeneity, finite‐element fault models invert the displacement data and simulate the dual‐fault geometry with non‐uniformly distributed shallow crustal materials. Our results suggest the west‐dipping SEAF and north‐dipping SCSF accommodate earthquake slips of >10 m. Their respective slip distributions and proximal aftershocks correlate spatially with local seismic velocity anomalies (i.e., ΔVp and ΔVs), which implies differences in structural control along these two faults and provides insights into assessing the seismic hazard of mixed incipient‐mature fault systems.

Ying Wei,1 Yan-Zhi Wang,2 Ying Li,1 Ling Liu,1 Ting-Ting Sui,2 Yuan Li1 1Department II of Anorectal Department, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of China; 2Department I of Anorectal Department, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of ChinaCorrespondence: Ying Wei, Department II of Anorectal Department, China-Japan Friendship Hospital, No. 2, Sakura East Street, Chaoyang District, Beijing, 100029, People’s Republic of China, Tel +86-01053236548, Email Yingwei_2023@163.comObjective: To explore the effect of comprehensive nursing on pain relief, comfort and burden of family care of infantile anal fistula.Methods: This was a randomized, double-blind, controlled clinical trial. A total of 106 cases of children with anal fistula from January 2021 to December 2021 were selected and divided into observation group and control group, there were 53 cases in each group. The control group were underwent with routine nursing intervention. The observation group were underwent with video health education, peer support, music relaxation training, physiotherapy and auricular point pressing on the basis of routine nursing therapy and other measures (comprehensive nursing). The wound healing time, comfort score, complication rate and family care burden of two groups were compared.Results: After intervention, the scores of pain degree in the observation group were significantly lower than those in the control group (4.02 ± 0.85 vs 5.89 ± 2.36, p < 0.05), and the scores of comfort degree in the observation group were higher than those in the control group (70.23 ± 5.98 vs 46.88 ± 5.23, p < 0.05). After intervention, the wound healing time of the observation group was shorter than that of the control group (3.98 ± 0.63 vs 5.77 ± 1.02, p < 0.05), and the crying times of the observation group were less than that of the control group (1.22 ± 0.26 vs 4.02 ± 0.48, p < 0.05). After intervention, the total scores of family members’ care load in the observation group were significantly lower than those in the control group (37.26 ± 4.78 vs 55.99 ± 5.02, p < 0.05).Conclusion: Comprehensive nursing can effectively promote wound healing in infantile anal fistula, reduce pain, prompt children’s comfort, reduce the number of children crying, and reduce the burden of care for children’s families.Keywords: comprehensive nursing, infantile anal fistula, comfort, complications, family care burden

Monitoring and predicting the dynamic responses of railway bridges under moving trains, including displacement and acceleration, are vital for evaluating the safety and serviceability of the train–bridge system. Traditionally, finite element analysis methods with high computational burden are used to predict the train-induced responses according to the given train loads and, hence, cannot easily be integrated as an available structural-health-monitoring strategy. Therefore, this study develops a novel framework, combining the train–bridge coupling mechanism and deep learning algorithms to efficiently predict the train-induced bridge responses while considering train load duration. Initially, the feasibility of using neural networks to calculate the train–bridge coupling vibration is demonstrated by leveraging the nonlinear relationship between train load and bridge responses. Subsequently, the instantaneous multiple moving axial loads of the moving train are regarded as the equivalent node loads that excite adjacent predefined nodes on the bridge. Afterwards, a deep long short-term memory (LSTM) network is established as a surrogate model to predict the train-induced bridge responses. Finally, the prediction accuracy is validated using a numerical case study of a simply supported railway bridge. The factors that may affect the prediction accuracy, such as network structure, training samples, the number of structural units, and noise level, are discussed. Results show that the developed framework can efficiently predict the train-induced bridge responses. The prediction accuracy of the bridge displacement is higher than that of the acceleration. In addition, the robustness of the displacement prediction is proven to be better than that of the acceleration with the variation of carriage number, riding speed, and measurement noise.

An improved method for the separation and purification of rubropunctatin from red yeast glutinous rice was developed. In this method, silica gel column chromatography and thin layer chromatography were used to separate the Monascus pigments. Pure methanol and a mixture of ethyl acetate and methanol (13:7, v/v) were selected as the eluent and running solvent, respectively. When compared with previously reported methods, the developed method required fewer types of solvents, and could be suitable for large-scale laboratory production. The extracted pigment was analysed by ultra-high performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-Q-TOF-MS) and nuclear magnetic resonance (NMR) (1H NMR, 13C NMR). Structural analysis revealed a molecular mass of 353.2 m/z [M-H]-, and a structure including an azaphilone body with two side chains. This structure was consistent with that reported for rubropunctatin. Therefore, the improved purification method reported herein could efficiently be used for the extraction of rubropunctatin from red yeast glutinous rice. [ABSTRACT FROM AUTHOR]

This paper focuses on the application of pile foundation underpinning technology in a deep foundation pit of a subway Viaduct Project in Beijing. The study aims to address the engineering characteristics of the project, including a large number of new piles, a wide span of underpinning abutment, a long length of deep foundation pit, and a wide range of influences. This research utilizes field monitoring and numerical simulation methods to investigate the pile foundation underpinnings. The impact and management of road-deep foundation pit construction are considered, as well as their combined effect on subway viaducts and track structures. The primary accomplishments are as follows: (1) By analyzing the data from on-site deformation monitoring, it is evident that the pier exhibits maximum vertical deformation and maximum transverse deformation at the same location. The measuring locations are specifically situated on Pier 7# at the pile foundation underpinning. The maximum vertical and transverse deformations of the track are directly proportional to the maximum deformation of the pier. (2) By comparing the numerical simulation results with the field monitoring data, it is observed that although there is some discrepancy between the two, the deformation trend is largely consistent. This suggests that the numerical simulation analysis method is effective in reflecting the deformation of the bridge and track. (3) Through the numerical model and changing the values of the retaining structure parameters, the sensitivity of the pier deformation near the road foundation pit to the retaining structure parameters is systematically analyzed. The sensitivity of the pier deformation to the foundation pit parameters is as follows: the embedded depth insertion ratio of the retaining pile > the diameter of the retaining pile > the pile spacing.

Abstract The Coronavirus Disease 2019 (COVID-19) has had a profound impact on global health and economy, making it crucial to build accurate and interpretable data-driven predictive models for COVID-19 cases to improve public policy making. The extremely large scale of the pandemic and the intrinsically changing transmission characteristics pose a great challenge for effectively predicting COVID-19 cases. To address this challenge, we propose a novel hybrid model in which the interpretability of the Autoregressive model (AR) and the predictive power of the long short-term memory neural networks (LSTM) join forces. The proposed hybrid model is formalized as a neural network with an architecture that connects two composing model blocks, of which the relative contribution is decided data-adaptively in the training procedure. We demonstrate the favorable performance of the hybrid model over its two single composing models as well as other popular predictive models through comprehensive numerical studies on two data sources under multiple evaluation metrics. Specifically, in county-level data of 8 California counties, our hybrid model achieves 4.173% MAPE, outperforming the composing AR (5.629%) and LSTM (4.934%) alone on average. In country-level datasets, our hybrid model outperforms the widely-used predictive models such as AR, LSTM, Support Vector Machines, Gradient Boosting, and Random Forest, in predicting the COVID-19 cases in Japan, Canada, Brazil, Argentina, Singapore, Italy, and the United Kingdom. In addition to the predictive performance, we illustrate the interpretability of our proposed hybrid model using the estimated AR component, which is a key feature that is not shared by most black-box predictive models for COVID-19 cases. Our study provides a new and promising direction for building effective and interpretable data-driven models for COVID-19 cases, which could have significant implications for public health policy making and control of the current COVID-19 and potential future pandemics.

Hong Kong women activists’ understanding of love and justice has shaped, and been shaped, by their political engagement under changing circumstances through two phases of mass protest: in 2014 and 2019. This article is focused on the sentiments of love and justice and how they evolved over time, from the peaceful protest of the Umbrella Movement in 2014 to the violent confrontations of 2019 in the context of the rise of ethno-nationalism. This shift reflects a changed understanding of justice – revenge against China – and a specific version of passionate love for Hong Kong and protective love for their comrades. Women activists’ experiences offer insights into how a social movement has engaged women’s emotional energies in particular gendered ways, while persistently marginalising gender issues. In the aftermath of the movement, when protest was effectively banned by both COVID-19 restrictions and the 2020 National Security Law, these women’s emotions have found a new object of their fierce love for Hong Kong: the boy band Mirror, which has come to symbolise Hongkonger pride, belonging and resistance.