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Introduction: Respiratory dysfunction in patients with Parkinson’s disease (PD) could present in the early stage and worsen in the late stages. These changes could be a factor affecting the ability of daily living and quality of life of patients with PD. The primary objective of this study was to assess the respiratory function and its association with motor function in patients with different stages of PD. Methods: This was a cross-sectional study conducted at the Huashan Hospital of Fudan University in Shanghai, China. The study included 65 patients diagnosed with PD (the Hoehn & Yahr scale between 1 and 4) and 20 healthy individuals of similar age, gender, weight and height. The ventilatory function was assessed using the spirometry. Motor function was evaluated using subscale III of the United Parkinson’s disease rating scale (UPDRS-III). After confirming the normality of data distribution, we performed one-way ANOVA with a Tukey’s post-hoc test. Results: Compared with the healthy individuals, there was no statistical significance in forced vital capacity (FVC), forced expiratory volume in 1s (FEV1) and forced expiratory volume in 1s/forced vital capacity (FEV1/FVC) in the H&Y 1 group and H&Y 2 group (P>0.05); but reduced peak expiratory flow (PEF) in the H&Y 2 group (P=0.002). Reduced FVC、FEV1 and PEF was seen in the H&Y3 group (P=0.002, P=0.001 and P=0.0001, respectively). Reduced FVC、FEV1、PEF and FEF25-75% was seen in the H&Y4 group (P=0.001, P=0.0001, P=0.0001 and P=0.025, respectively). The correlation analysis revealed that there was a significant negative correlation between FVC and UPDRS-III scores (r=-0.248, P=0.046), disease duration (r=-0.276, P=0.026), H&Y scale (r=-0.415, P=0.001). FEV1 was negatively correlated with UPDRS-III scores (r=-0.277, P=0.025), disease duration (r=-0.291, P=0.019), H&Y scale (r=-0.434, P=0.0001). FEF25%-75% was negatively correlated with disease duration (r=-0.247, P=0.047), H&Y scale (r=-0.278, P=0.025). Conclusion: Our findings revealed that respiratory impairment is present in moderate and advanced PD patients, and directly related to the severity of the disease. It is important to conduct respiratory function test in the clinical practice.

As a country of rich bamboo forest and large-scale bamboo processing industry, China is promoting the development of modified bamboo building materials and the bamboo construction systems. In the study on bamboo building envelope (BBE), as a hygroscopic construction, particular attention should be paid to the coupled heat and moisture (H&M) process. However, the parameters basis and the thermal design code in China could not yet support such calculation on coupled H&M process of BBE. In order to clarify the impact of meteorological parameters on the H&M process of BBE, the study prepares 24 representative cities in China with climate data exported from the Meteonorm platform and 3 typical bamboos with complete material properties data tested through experiments, and then sets up comparison BBE model groups in the software WUFI Plus for annual H&M process simulation. Statistical analysis clarifies the correlation law between the H&M process of BBE and the meteorological parameters. The study highlights the importance of hygric meteorological data for the application of BBE.

The self-reported quality of life (QoL) should be carefully listened to in progressive supranuclear palsy (PSP) from the patient-centered perspective. However, there was still a lack of short QoL measurement tool in atypical parkinsonism.We aimed to test whether the short Parkinson's Disease Questionnaire-8 (PDQ-8) was effective in assessing QoL in PSP, comparing with Progressive Supranuclear Palsy Quality of Life Scale (PSP-QoL) and Parkinson's Disease Questionnaire-39 (PDQ-39).132 patients with clinical diagnosed PSP, including PSP-Richardson syndrome (RS) subtype (n = 71) and PSP-non-RS subtype (n = 61) were recruited for clinical evaluation including QoL assessment. The detailed QoL profiles and possibility of using PDQ-8 were systemically analyzed. The determinants to the QoL were then calculated by multivariate linear regression analysis.The PSP-QoL total score summary index (SI) was 22.8 (10.1, 41.1), while the PDQ-8 and PDQ-39 total SI score were 28.1 (12.5, 46.9) and 29.5 (15.4, 49.4). Mobility, activities of daily life, cognition and communication were the main affected QoL subdomains (median SI: 40.0, 31.3, 25.0 and 25.0 respectively). PSP-RS subtype showed more severe damage physically (p0.001) and mentally (p = 0.002) compared to other subtypes. More importantly, the strong relevance of PDQ-8 and recommended PSP QoL tools were confirmed (p0.001). In addition, disease severity, depression and daytime sleepiness were proved to be critical determinants for QoL in PSP.PDQ-8 could be an easy, reliable, and valid tool to evaluate QoL in patients with PSP. Besides motor symptoms, more attention should be paid to non-motor impairment such as depression in PSP.

BACKGROUND Frontotemporal lobar degeneration with tauopathy caused by MAPT (microtubule-associated protein tau) mutations is a highly heterogenous disorder. The ability to visualize and longitudinally monitor tau deposits may be beneficial to understand disease pathophysiology and predict clinical trajectories. OBJECTIVE The aim of this study was to investigate the cross-sectional and longitudinal 18 F-APN-1607 positron emission tomography/computed tomography (PET/CT) imaging findings in MAPT mutation carriers. METHODS Seven carriers of MAPT mutations (six within exon 10 and one outside of exon 10) and 15 healthy control subjects were included. All participants underwent 18 F-APN-1607 PET/CT at baseline. Three carriers of exon 10 mutations received follow-up 18 F-APN-1607 PET/CT scans. Standardized uptake value ratio (SUVR) maps were obtained using the cerebellar gray matter as the reference region. SUVR values observed in MAPT mutation carriers were normalized to data from healthy control subjects. A regional SUVR z score ≥ 2 was used as the criterion to define positive 18 F-APN-1607 PET/CT findings. RESULTS Although the seven study patients had heterogenous clinical phenotypes, all showed a significant 18 F-APN-1607 uptake characterized by high-contrast signals. However, the anatomical localization of tau deposits differed in patients with distinct clinical symptoms. Follow-up imaging data, which were available for three patients, demonstrated worsening trends in patterns of tau accumulation over time, which were paralleled by a significant clinical deterioration. CONCLUSIONS Our data represent a promising step in understanding the usefulness of 18 F-APN-1607 PET/CT imaging for detecting tau accumulation in MAPT mutation carriers. Our preliminary follow-up data also suggest the potential value of 18 F-APN-1607 PET/CT for monitoring the longitudinal trajectories of frontotemporal lobar degeneration caused by MAPT mutations. © 2021 International Parkinson and Movement Disorder Society.

Background 18 F-APN-1607 is a novel tau PET tracer characterized by high binding affinity for 3- and 4-repeat tau deposits. Whether 18 F-APN-1607 PET imaging is clinically useful in PSP remains unclear. Objectives The objective of this study was to investigate the clinical utility of 18 F-APN-1607 PET in the diagnosis, differential diagnosis, and assessment of disease severity in patients with PSP. Methods We enrolled 3 groups consisting of patients with PSP (n = 20), patients with α-synucleinopathies (MSA with predominant parkinsonism, n = 7; PD, n = 10), and age- and sex-matched healthy controls (n = 13). The binding patterns of 18 F-APN-1607 in PET/CT imaging were investigated. Regional standardized uptake ratios were compared across groups and examined in relation to their utility in the differential diagnosis of PSP versus α-synucleinopathies. Finally, the relationships between clinical severity scores and 18 F-APN-1607 uptake were investigated after adjustment for age, sex, and disease duration. Results Compared with healthy controls, patients with PSP showed increased 18 F-APN-1607 binding in several subcortical regions, including the striatum, putamen, globus pallidus, thalamus, subthalamic nucleus, midbrain, tegmentum, substantia nigra, pontine base, red nucleus, raphe nuclei, and locus coeruleus. We identified specific regions that were capable of distinguishing PSP from α-synucleinopathies. The severity of PSP was positively correlated with the amount of 18 F-APN-1607 uptake in the subthalamic nucleus, midbrain, substantia nigra, red nucleus, pontine base, and raphe nuclei. Conclusions 18 F-APN-1607 PET imaging holds promise for the diagnosis, differential diagnosis, and assessment of disease severity in patients with PSP. © 2021 International Parkinson and Movement Disorder Society.

Idiopathic rapid eye movement sleep behaviour disorder (RBD) is now recognized as an early manifestation of α-synucleinopathies. Increasing experimental studies demonstrate that manipulative lesion or inactivation of the neurons within the sublaterodorsal tegmental nucleus (also known as the subcoeruleus nucleus in humans) can induce RBD-like behaviours in animals. As current RBD animal models are not established on the basis of α-synucleinopathy, they do not represent the pathological substrate of idiopathic RBD and thus cannot model the phenoconversion to Parkinson’s disease. The purpose of this study was therefore to establish an α-synucleinopathy-based RBD animal model with the potential to convert to parkinsonian disorder. To this end, we first determined the functional neuroanatomical location of the sublaterodorsal tegmental nucleus in wild-type C57BL/6J mice and then validated its function by recapitulating RBD-like behaviours based on this determined nucleus. Next, we injected preformed α-synuclein fibrils into the sublaterodorsal tegmental nucleus and performed regular polysomnographic recordings and parkinsonian behavioural and histopathological studies in these mice. As a result, we recapitulated RBD-like behaviours in the mice and further showed that the α-synucleinopathy and neuron degeneration identified within the sublaterodorsal tegmental nucleus acted as the neuropathological substrates. Subsequent parkinsonian behavioural studies indicated that the α-synucleinopathy-based RBD mouse model were not stationary, but could further progress to display parkinsonian locomotor dysfunction, depression-like disorder, olfactory dysfunction and gastrointestinal dysmotility. Corresponding to that, we determined α-synuclein pathology in the substantia nigra pars compacta, olfactory bulb, enteral neuroplexus and dorsal motor nucleus of vagus nerve, which could underlie the parkinsonian manifestations in mice. In conclusion, we established a novel α-synucleinopathy-based RBD mouse model and further demonstrated the phenoconversion of RBD to Parkinson’s disease in this animal model.

Background There was a paucity of follow-up studies in the disease progression of early-onset PD patients with Parkin mutations (Parkin-EOPD). Here we conducted a longitudinal study to investigate the progression of motor and cognitive features of Parkin-EOPD patients. Methods Genetic analysis was performed via target sequencing and multiplex ligation-dependent probe amplification. Thirty patients carrying homozygous or compound heterozygous Parkin mutations with at least 2 follow-up revisions were investigated as the Parkin-EOPD group. Fifty-two patients with at least 2 follow-up revisions, who did not have any known causative PD mutations, GBA or LRRK2 risk variants, a heterozygous Parkin mutation or 2 Parkin mutations without a segregation test, were defined as the genetically undefined EOPD (GU-EOPD) group. A linear mixed-effect model was implemented to evaluate longitudinal changes in motor symptoms and cognition. Results At baseline, the Parkin-EOPD group had a lower Unified Parkinson's Disease Rating Scale score (UPDRS-III) (off-medication) than the GU-EOPD group, without significant differences in cognition. A longitudinal study showed the estimated progression rate per year (standard error) of the UPDRS-III score (off-medication) was lower in the Parkin-EOPD group (0.203 [0.3162] points per year) than in the GU-EOPD group (1.056 [0.3001] points per year). The difference in the UPDRS-III score rate between the 2 groups was 0.853 (0.4183) (P = 0.042). The Parkin-EOPD group showed better maintenance of spatial processing ability compared with the GU-EOPD group (P = 0.027). Conclusion Parkin-EOPD patients showed a slower deterioration of motor symptoms and a better spatial processing ability than GU-EOPD patients, which suggests that subtyping according to genetic features can help predict PD progression. © 2020 International Parkinson and Movement Disorder Society.

Previous studies with a limited sample size suggested more severe dopaminergic transporter (DAT) lesions in the striatum of progressive supranuclear palsy (PSP) than those in Parkinson's disease (PD) and multiple system atrophy-parkinsonism (MSA-P). However, few studies had taken various subtypes of PSP into consideration, making the reanalysis of DAT imaging in larger PSP cohort with various subtypes in need.To compare the dopaminergic lesion patterns of PSP with MSA-P and PD, and to explore the specific striatal subregional patterns of different PSP subtypes.The patients with PSP presented more severe DAT loss in the striatum than in PD and MSA-P, especially in caudate. In PSP, the subregional lesion was still more severe in putamen than in caudate, similar to that in PD and MSA-P. Among detailed subtypes, no significant difference was detected.The dopaminergic lesions were more severe in PSP, and no difference was detected among subtypes.

Basalt fiber reinforced fly ash concrete (BFRFAC) is a new inorganic non-metal composite building material with superior mechanical performance, which can be extensively applied in the fields of bridge floors, pavements and other construction engineering projects. In the present paper, the freezing and thawing resistance performance of BFRFAC under corrosion conditions was studied in detail with the comparison to the Normal Concrete (NC). Experimental studies on the mass loss rate (MLR) in a non-corrosive environment, and the MLR as well as the relative dynamic modulus of elasticity (RDME) in chlorine corrosion, sulfate corrosion and the complex combined corrosion of chloride and sulfate solution were conducted through the quick freezing method. Further, the meso-structure of the fracture section in the composite material was scanned with the help of a scanning electron microscope (SEM) at amplified ×500, ×1,000 and ×1,500. The gripping effect between basalt fibers and substrate under the case of pull-out failure and fracture failure was quantitatively analyzed, which convincingly revealed the crack resistance, reinforcement and strengthening mechanisms of basalt fibers on concrete substrate. The research results indicated that RDME decreased and its decent rate became slower in turn when the composite material was exposed to freeze-thaw cycles in all the above four considered cases. Among them, in the case of the complex solution corrosion, the number of freeze-thaw cycles of BFRFAC was larger than 400. Compared to the NC, the BFRFAC cyclic lifespan could be extended effectively. In addition, the full play of fly ash activity and great filling effect enhanced the gripping effect between basalt fibers and concrete substrate. Therefore, it could effectively improve the freezing and thawing resistance damage capacity of BFRFAC.

In terms of Pb isotope ratios, melting anomalies of Central and East Asia show no high μ (HIMU, high 238U/204Pb) signature that was generated on the Earth about 2 Ga ago and was caused by sulfide sequestration of Pb from the mantle to the core [Hart and Gaetany, 2006]. In such particular environment, we use Pb isotope data on Late Phanerozoic volcanic rocks to develop general systematics of their sources through definition of initial viscous protomantle reservoirs with low μ and elevated μ signatures (LOMUVIPMAR and ELMUVIPMAR, respectively) that imply a solidification time of the mantle in the Hadean magma ocean between 4.54 and 4.44 Ga ago. We suggest that the protomantle reservoirs retained specific Pb isotope signatures in the early, middle, and late epochs of the Earth's evolution (4.54–3.6, 2.9–1.8, and Hart, S.R. & Gaetani, G.A. (2006). Mantle paradoxes: the sulfide solution. Contrib. Mineral. Petrol., 152, 295–308.Rasskazov, S., Chuvashova, I., Yasnygina, T., & Saranina, E. (2020). Mantle evolution of Asia inferred from Pb isotopic signatures of sources for Late Phanerozoic volcanic rocks. Minerals, 10 (9), 739.

Mutations in Presenilin-1 (PSEN1) have been found to be associated with very early onset Alzheimer’s disease (VEOAD). Here, we reported two patients with VEOAD caused by de novo PSEN1 mutations. A 33-year-old man with a de novo p.F177S mutation in PSEN1 presented with progressive decline in memory and daily function. A 37-year-old woman with a de novo PSEN1 p.L381V mutation presented with onset memory impairment, developed cerebellar syndrome, rigidity, and spastic paraparesis. The Amyloid/Tau/Neurodegeneration (ATN) biomarker profiles of both patients were A + T + (N)+. Our finding increases the genetic knowledge of VEOAD and extends the ethnic distribution of PSEN1 mutations.

Background Pathogenic mutations in the TANK-binding kinase 1 (TBK1) gene have been associated with progressive supranuclear palsy (PSP)-like extrapyramidal symptoms, amyotrophic lateral sclerosis (ALS), as well as cognitive and behavioral alterations. However, the question as to whether TBK1 mutations may be associated with tau burden remains unanswered. Methods To investigate whether patients presenting with PSP-like extrapyramidal symptoms caused by TBK1 mutations have evidence of tau deposition as reflected by positive 18F-APN-1607 tau PET imaging findings. Four patients who showed PSP-like extrapyramidal symptoms, ALS, and cognitive/behavioral alterations were consecutively enrolled between August 2019 and August 2020. Patients underwent TBK1 gene sequencing and 18F-APN-1607 tau PET imaging. All PET images were interpreted in a blinded fashion with respect to genetic results. Brain structural changes were investigated with MRI, whereas 11C-CFT or 18F-DTBZ PET imaging was performed to identify dopaminergic degeneration. Results Pathogenic TBK1 mutations were identified in three of the four study patients. The three mutation carriers – but not the case without – showed positive 18F-APN-1607 binding in PSP-related regions, suggesting the presence of tau pathology. Mesencephalic atrophy (hummingbird sign) was observed in all TBK1 mutation carriers, and two of them also had evidence of frontotemporal atrophy. Dopaminergic degeneration was evident in all cases, regardless of TBK1 mutations. Conclusions Pathogenic TBK1 mutations in patients with PSP-like extrapyramidal symptoms are associated with positive 18F-APN-1607 tau PET imaging findings. Our data should prompt additional investigations on the potential role of tau accumulation in the pathogenesis of disease conditions associated with TBK1 mutations.

α-Synuclein (α-syn) fibrillar aggregates are the major component of Lewy bodies and Lewy neurites presenting as the pathology hallmark of Parkinson’s disease (PD). Studies have shown that α-syn is potential to form different conformational fibrils associated with different synucleinopathies, but whether the conformation of α-syn fibrils changes in different phases of related diseases is to be explored. Here, we amplified α-syn aggregates from the cerebrospinal fluid (CSF) of preclinical (pre-PD) and late-stage postmortem PD (post-PD) patients. Our results show that compared to the CSF of pre-PD, that of post-PD is markedly stronger in seeding in vitro α-syn aggregation, and the amplified fibrils are more potent in inducing endogenous α-syn aggregation in neurons. Cryo-electron microscopic structures further reveal that the difference between the pre-PD- and post-PD-derived fibrils lies on a minor polymorph which in the pre-PD fibrils is morphologically straight, while in the post-PD fibrils represents a single protofilament assembled by a distinctive conformation of α-syn. Our work demonstrates structural and pathological differences between pre-PD and post-PD α-syn aggregation and suggests potential alteration of α-syn fibrils during the progression of PD clinical phases.Significance StatementIncreasing evidence support different conformational α-syn fibrils in patients with different α-synucleinopathies, but whether the conformation of α-syn fibrils changes in different phases of related diseases is unknown. Here, we show that α-syn fibrils amplified from the cerebrospinal fluid (CSF) of the late-stage postmortem PD (post-PD) patient are more potent in inducing endogenous α-syn aggregation in neurons than that amplified from the preclinical (pre-PD) patient. Cryo-EM structures further reveal that the post-PD fibrils contain a novel conformation that is distinct from either the pre-PD fibrils or those previously reported. Our work suggests conformational evolution of α-syn fibrils along with PD progression.

Objective New subtyping classification systems of Parkinson’s disease (PD) have been proposed for phenotyping patients into three different subtypes: mild motor‐predominant (PD‐MMP), intermediate (PD‐IM) and diffuse malignant (PD‐DM). The quality of life (QoL) underlying the novel PD clinical subtypes is unknown. This study aimed explore the feasibility of the classification in Chinese PD patients and to investigate the potential heterogeneous determinants of QoL among the three subtypes. Methods 298 PD patients were enrolled, including 129 PD‐MMP patients, 121 PD‐IM patients and 48 PD‐DM patients. All patients completed the QoL assessment, clinical evaluations and neuropsychological tests. Univariate linear analysis and multiple stepwise regression analysis were performed to identify determinants of QoL. Results Compared to PD‐MMP patients, PD‐IM and PD‐DM patients had more impaired QoL. The Geriatric Depression Rating Scale (GDS) score, Non‐Motor Symptoms Questionnaire (NMSQ) score, Unified Parkinson’s Disease Rating Scale part III (UPDRS‐III) score and Epworth Sleepiness Score (ESS) were independent contributors to QoL in PD‐MMP patients. The GDS score, ESS and sniffin’ sticks screening 12 test score were independent contributors to QoL in PD‐IM patients. The GDS score and Mini Mental State Examination score were independent contributors to QoL in PD‐DM patients. Interpretation The new novel subtyping classification is feasible for Chinese PD patients. Although depression was the most crucial determinant for QoL in PD‐MMP, PD‐IM and PD‐DM patients, the other contributors of QoL in the three subtypes were heterogeneous. These findings may prompt clinicians to target specific factors for improving QoL depending on PD subtypes.

Improvement of quality-of-life (QoL) has been termed as a primary objective in initiating therapy in both Parkinson’s disease (PD) and multiple system atrophy Parkinsonian subtype (MSA-P). We aimed to compare the determinants of life quality in drug naive PD and MSA-P patients. Eighty-six drug-naive PD patients and thirty-five drug-naive MSA-P patients were included to explore the determinants of QoL. Demographic information, motor deficits, and non-motor symptoms were included in the clinical assessment. Both motor and non-motor functions were more severely impaired in the drug-naive MSA-P patients, with higher PDQ-39 scores indicating poorer QoL. Physical discomfort and stigma were the main affected sub-domains in PD, while mobility and activity of daily life were the main affected ones in MSA-P. BECK depressive scores and UPDRS-III scores were independent variables of PDQ-39 in MSA-P patients. Age, depression, disease stages and non-motor scores were independent variables of PDQ-39 in PD patients. Drug-naive MSA-P patients suffered from more severe motor and non-motor disability, as well as poorer QoL. Depression and non-motor symptoms were proved to be the most critical determinants for QoL in PD, while motor function was supposed to be the major determinant for MSA-P. When initiating therapy, physicians need to focus more on motor functions in drug-naive MSA-P patients, but on depression in PD patients.

Frontotemporal lobar degeneration with tauopathy caused by MAPT (microtubule-associated protein tau) mutations is a highly heterogenous disorder. The ability to visualize and longitudinally monitor tau deposits may be beneficial to understand disease pathophysiology and predict clinical trajectories.The aim of this study was to investigate the cross-sectional and longitudinalSeven carriers of MAPT mutations (six within exon 10 and one outside of exon 10) and 15 healthy control subjects were included. All participants underwentAlthough the seven study patients had heterogenous clinical phenotypes, all showed a significantOur data represent a promising step in understanding the usefulness of

The objective of this study was to investigate the clinical utility ofWe enrolled 3 groups consisting of patients with PSP (n = 20), patients with α-synucleinopathies (MSA with predominant parkinsonism, n = 7; PD, n = 10), and age- and sex-matched healthy controls (n = 13). The binding patterns ofCompared with healthy controls, patients with PSP showed increased

A 39-year-old man presented with worsening slurred speech, difficulty walking, and falls for 2 years. Examination found severe ataxia and enlargement of Achilles tendons. Brain CT demonstrated modest hyperdensity in cerebellar hypodense lesions. T2-weighted imaging revealed hypointensity in deep cerebellar white matter, more evident on susceptibility-weighted imaging. Magnetic resonance spectroscopy suggested lipid storage and mitochondrial dysfunction. The diagnosis of cerebrotendinous xanthomatosis (CTX) was confirmed by gene screening of CYP27A1 (Figure) .

Potassic rocks from the Wudalianchi field are considered by some authors as derivatives of the mantle transition layer. However, this opinion is contradicted by the contrasting component composition of melts erupted in different volcanoes. From data of lead isotope compositions, the initial eruptions of lava flows 2.5–2.0 Ma ago were derived from the lithospheric Laoshantou and Gelaqiu model sources of about 1.88 Ga, while subsequent eruptions were derived from the Wohu source of about 0.15 Ga and the recent Molabu source (Rasskazov et al., 2020). Detailed sampling of volcanoes yielded geochemical evidence on both the individualization of sources beneath volcanoes and mixing of melts from contrasting sources. We present evidence on mixing of melts from the Gelaqiu, Wuhu, and Molabu sources beneath the Jiaodebushan Volcano and partial similarity of rock components from this volcano to material erupted in the Xiaogushan Volcano.This work is supported by the RSF grant 18-77-10027.Rasskazov S., Sun Y-M., Chuvashova I., Yasnygina T., Yang C., Xie Z., Saranina E., Gerasimov N., Vladimirova T. Trace-element and Pb isotope evidence on extracting sulfides from potassic melts beneath Longmenshan and Molabushan volcanoes, Wudalianchi, Northeast China. Minerals. 2020. V. 10: 319; doi:10.3390/min10040319

BACKGROUND Parkinson's disease (PD) is the second most common neurodegenerative disorder, but the disease-modifying therapies focusing on the core pathological changes are still unavailable. Rho-associated protein kinase (ROCK) has been suggested as a promising target for developing neuroprotective therapies in PD. OBJECTIVE We aimed to explore the promotion of α-synuclein (α-syn) clearance in a rat model. METHODS In a rat model induced by unilateral injection of adeno-associated virus of serotype 9 (AAV9) expressing A53T α-syn (AAV9-A53T-α-syn) into the right substantia nigra, we aimed to investigate whether Fasudil could promote α-syn clearance and thereby attenuate motor impairments and dopaminergic deficits. RESULTS In our study, treatment with Fasudil (5 mg/kg rat weight/day) for 8 weeks significantly improved the motor deficits in the Cylinder and Rotarod tests. In the in vivo positron emission tomography imaging with the ligand 18F-dihydrotetrabenazine, Fasudil significantly enhanced the dopaminergic imaging in the injected striatum of the rat model (p

On the diagram of uranogenic leads, we define 1.88 Byr locus of lithospheric sources for low-Mg rocks from Wudalianchi and a non-lithospheric recently homogenized material (referred to the Molabu source) for moderate-Mg rocks. Lithosphere-derived liquids were characteristic of the initial Laoshantou and Old Gelaqiushan lava flows erupted along a north-south volcanic line 2.5–2.0 Myr ago. Due to eastward expansion of the Wudalianchi melting anomaly, its NNE limit was designated by lithosphere-derived liquids erupted in North Gelaqiushan and Weishan volcanoes between 0.6 and 0.4 Myr ago. In the evolution of the melting anomaly, other volcanoes showed compositions derived due to mixing lithospheric and non-lithospheric components. The only exception was moderate-Mg rocks from East Longmenshan volcano that yielded peculiar compositions modified after liquids from the Molabu source. Decreasing Pb, S, and Ni abundances, Ni/Co, Ni/MgO ratios as well as increasing 206Pb/204Pb, 207Pb/204Pb, 208Pb/204Pb, Ce/Pb, Th/Pb, and U/Pb ratios are indicative for liquids likely affected by segregating small amounts of sulfide droplets. We infer that the Wudalianchi melting anomaly was firstly generated in the lithosphere and was evolved to melting of the sub-lithospheric medium.This work is supported by the RSF grant 18-77-10027.

Hepatic progenitor cells (HPCs) are a subpopulation of cells which was usually expanded in chronic liver injury and are contributed to liver regeneration through differentiating into hepatocytes and cholangiocytes. Epithelial-mesenchymal transition is a dynamic process which is important for the progression of liver fibrosis and cancer initiation. This study demonstrated that LE/6 and WB-F344 cells, both of which were HPC derived cell lines, were undergoing partial epithelial-mesenchymal transition states, which was indicated by the co-expression of epithelial markers (E-cadherin and zona occludin 1), and mesenchymal markers (vimentin, fibronectin, collagen 1and α-SMA). Furthermore, autocrine TGF-β and activin A signaling contributed to the maintenance of partial EMT in HPCs. In addition, Smad signaling, a classic downstream signaling cascade of both TGF-β and activin A, also participated in the partial EMT. These findings revealed the existence of partial EMT states in HPCs and confirmed some partial EMT related autocrine signaling cascades, and may help to further the understanding and explore the functional role of HPCs in the process of hepatic fibrosis and liver cancer initiation.

The mutation of vesicle-associated membrane protein-associated protein B (VAPB) was proved to cause family amyotrophic lateral sclerosis (FALS). Only two mutations of VAPB associated with ALS have been reported (p.Pro56Ser and p.Thr46Ile). Here we reported a Chinese Han FALS family caused by a novel VAPB point mutation. The clinical materials of one Chinese Han FALS family were collected. The genetic analysis was carried out by target sequencing and further verified by Sanger sequencing. One novel mutation of c.167C>A (p.Pro56His) on VAPB was found in the proband. The age at onset of the proband was 48 with the onset symptoms of weakness in the right arm, followed by progressive limb and trunk weakness with decreased deep-tendon reflexes, muscular cramps and fasciculation. But the disease duration was more than 15 years. He was under the tracheotomy for 1 year at last visit. Electromyography showed widespread acute and chronic neurogenic damages. His mother presented weakness in her limbs in 50 s and died 15 years later. One of his younger sisters diagnosed as ALS for 6 years also carried the same mutation. She presented the similar symptoms on 41. No dominant upper motor neuron sign was showed. The clinical features were similar to the patients carrying the known mutation of p.Pro56Ser. A novel mutation of VAPB was found in one Chinese Han FALS pedigree. The affected patients presented a much slower progression and the lesions were limited in lower motor neurons.

Over the centuries, people have used healing mud (peloids) to draw toxins out of the body, boost the immune system, cure psoriasis, acne, depression, and hair loss. The beauty industry has used mud-clay masks, body wraps, soaps, and baths. The useful properties of mud were established empirically. The most popular healing-mud spars are known in the Dead Sea in Israel, Baden-Baden in Germany, Calistoga in California, Budapest in Hungary, Akhtala and Kumisi in Georgia, Paratunka in Kamchatka, Wudalianchi in China.

At the latest geodynamic stage that is characterized by forces and processes of the last 90 Ma the lithosphere of Asia has been reactivated due to four main force factors: 1) mantle melting anomalies, 2) subduction-related interaction between the Pacific plates and the continental eastern margin, 3) convergent interaction between India and the continental southern margin, and 4) quasiperiodic orbital variations of the Earth. The starting point of the latest geodynamic stage [Rasskazov, Chuvashova, 2013] is consistent with the change of the Earth’s rotation due to the resonant interaction of its orbit with the orbit of the Mars in the time interval of 87–85 Ma [Ma et al., 2017].