Intestinal microbiota via NLRP3 inflammasome dependent neuronal pyroptosis mediates anxiety-like behaviour in mice exposed to 3.5 GHz radiofrequency radiation.

The rapid development of 5G communication technology has increased public concern about the potential adverse effects on human health. Till now, the impacts of radiofrequency radiation (RFR) from 5G communication on the central nervous system and gut-brain axis are still unclear. Therefore, we investigated the effects of 3.5 GHz (a frequency commonly used in 5G communication) RFR on neurobehavior, gut microbiota, and gut-brain axis metabolites in mice. The results showed that exposure to 3.5 GHz RFR at 50 W/m2 for 1 h over 35 d induced anxiety-like behaviour in mice, accompanied by NLRP3-dependent neuronal pyroptosis in CA3 region of the dorsal hippocampus. In addition, the microbial composition was widely divergent between the sham and RFR groups. 3.5 GHz RFR also caused changes in metabolites of feces, serum, and brain. The differential metabolites were mainly enriched in glycerophospholipid metabolism, tryptophan metabolism, and arginine biosynthesis. Further correlation analysis showed that gut microbiota dysbiosis was associated with differential metabolites. Based on the above results, we speculate that dysfunctional intestinal flora and metabolites may be involved in RFR-induced anxiety-like behaviour in mice through neuronal pyroptosis in the brain. The findings provide novel insights into the mechanism of 5G RFR-induced neurotoxicity.

Repetitive transcranial magnetic stimulation ameliorates cognitive deficits in mice with radiation-induced brain injury by attenuating microglial pyroptosis and promoting neurogenesis via BDNF pathway.

BACKGROUND: Radiation-induced brain injury (RIBI) is a common and severe complication during radiotherapy for head and neck tumor. Repetitive transcranial magnetic stimulation (rTMS) is a novel and non-invasive method of brain stimulation, which has been applied in various neurological diseases. rTMS has been proved to be effective for treatment of RIBI, while its mechanisms have not been well understood. METHODS: RIBI mouse model was established by cranial irradiation, K252a was daily injected intraperitoneally to block BDNF pathway. Immunofluorescence staining, immunohistochemistry and western blotting were performed to examine the microglial pyroptosis and hippocampal neurogenesis. Behavioral tests were used to assess the cognitive function and emotionality of mice. Golgi staining was applied to observe the structure of dendritic spine in hippocampus. RESULTS: rTMS significantly promoted hippocampal neurogenesis and mitigated neuroinflammation, with ameliorating pyroptosis in microglia, as well as downregulation of the protein expression level of NLRP3 inflammasome and key pyroptosis factor Gasdermin D (GSDMD). BDNF signaling pathway might be involved in it. After blocking BDNF pathway by K252a, a specific BDNF pathway inhibitor, the neuroprotective effect of rTMS was markedly reversed. Evaluated by behavioral tests, the cognitive dysfunction and anxiety-like behavior were found aggravated with the comparison of mice in rTMS intervention group. Moreover, the level of hippocampal neurogenesis was found to be attenuated, the pyroptosis of microglia as well as the levels of GSDMD, NLRP3 inflammasome and IL-1ß were upregulated. CONCLUSION: Our study indicated that rTMS notably ameliorated RIBI-induced cognitive disorders, by mitigating pyroptosis in microglia and promoting hippocampal neurogenesis via mediating BDNF pathway.

Effects of radiofrequency field from 5G communication on fecal microbiome and metabolome profiles in mice.

With the rapid development of 5G networks, the influence of the radiofrequency field (RF) generated from 5G communication equipment on human health is drawing increasing attention in public. The study aimed at assessing the effects of long-term exposure to 4.9 GHz (one of the working frequencies of 5G communication) RF field on fecal microbiome and metabolome profiles in adult male C57BL/6 mice. The animals were divided into Sham group and radiofrequency group (RF group). For RF group, the mice were whole body exposed to 4.9 GHz RF field for three weeks, 1 h/d, at average power density (PD) of 50 W/m2. After RF exposure, the mice fecal samples were collected to detect gut microorganisms and metabolites by 16S rRNA gene sequencing and LC-MS method, respectively. The results showed that intestinal microbial compositions were altered in RF group, as evidenced by reduced microbial diversity and changed microbial community distribution. Metabolomics profiling identified 258 significantly differentially abundant metabolites in RF group, 57 of which can be classified to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Besides, functional correlation analysis showed that changes in gut microbiota genera were significantly correlated with changes in fecal metabolites. In summary, the results suggested that altered gut microbiota and metabolic profile are associated with 4.9 GHz radiofrequency exposure.

Effects of X-ray cranial irradiation on metabolomics and intestinal flora in mice.

Cranial radiotherapy is an important treatment for intracranial and head and neck tumors. To investigate the effects of cranial irradiation (C-irradiation) on gut microbiota and metabolomic profile, the feces, plasma and cerebral cortex were isolated after exposing mice to cranial X-ray irradiation at a dose rate of 2.33 Gy/min (5 Gy/d for 4 d consecutively). The gut microorganisms and metabolites were detected by 16 S rRNA gene sequencing method and LC-MS method, respectively. We found that compared with sham group, the gut microbiota composition changed at 2 W and 4 W after C-irradiation at the genus level. The fecal metabolomics showed that compared with Sham group, 44 and 66 differential metabolites were found to be annotated into metabolism pathways at 2 W and 4 W after C-irradiation, which were significantly enriched in the arginine and proline metabolism. Metabolome analysis of serum and cerebral cortex showed that, at 4 W after C-irradiation, the expression pattern of metabolites in serum samples of mice was similar to that of sham group, and the cerebral cortex metabolites of the two groups were completely separated. KEGG functional analysis showed that serum and brain tissue differential metabolites were respectively enriched in tryptophan metabolism, and arginine proline metabolism. The correlation analysis showed that the changes of gut microbiota genera were significantly correlated with the changes of metabolism, especially Helicobacter, which was significantly correlated with many different metabolites at 4 W after C-irradiation. These data suggested that C-irradiation could affect the gut microbiota and metabolism profile, even at relatively long times after C-irradiation.

Coverage and impact of influenza vaccination among children in Minhang District, China, 2013-2020.

Background: Young children have a great disease burden and are particularly vulnerable to influenza. This study aimed to assess the direct effect of influenza vaccination among children and to evaluate the indirect benefit of immunizing children. Methods: The influenza vaccination records for all children born during 2013-2019 in Minhang District and surveillance data for reported influenza cases were obtained from the Minhang CDC. 17,905 children were recorded in the vaccination system and included in this study. Descriptive epidemiology methods were used for data analysis, including an ecological approach to estimate the number of influenza cases averted by vaccination and linear regression to estimate the reduction in influenza cases in the general population per thousand additional childhood vaccination doses. Results: During the study period, the annual vaccination coverage rate ranged from 10.40% in 2013-2014 to 27.62% in 2015-2016. The estimated number of influenza cases averted by vaccination ranged from a low of 0.28 (range: 0.23-0.34) during 2013-2014 (PF: 6.15%, range: 5.11-7.38%) to a high of 15.34 (range: 12.38-18.51) during 2017-2018 (PF: 16.54%, range: 13.79-19.30%). When increasing vaccination coverage rate by 10% in each town/street, a ratio of 7.27-10.69% cases could be further averted on the basis of observed cases. In four selected periods, the number of influenza cases in the general population was most significantly correlated with the cumulative childhood vaccination doses in the prior 2-5 months, and the reduction in influenza cases ranged from 0.73 to 3.18 cases per thousand additional childhood vaccination doses. Conclusion: Influenza vaccination among children is estimated to have direct effects in terms of averted cases and might provide an underlying indirect benefit to the general population. Vaccination coverage in high-coverage areas should be further expanded to avert more influenza cases.

Epidemiological characteristics of paediatric Omicron infection during the outbreak of SARS-CoV-2 infection during March-May in 2022 in Shanghai, China.

This study aims to understand the epidemiological characteristics of SARS-CoV-2 infection in the paediatric population during the outbreak of the Omicron variant in Shanghai. We retrospectively analysed the population-based epidemiological characteristics and clinical outcome of SARS-CoV-2 Omicron variant infection in children in Minhang District, Shanghai, based on the citywide surveillance system during the outbreak period in 2022 (March to May). During this time, a total of 63,969 cases of SARS-CoV-2 infection were notified in Minhang District, out of which 4,652 (7.3%) were children and adolescents <18 years. The incidence rate of SARS-CoV-2 infections in children was 153 per 10,000. Of all paediatric cases, 50% reported to be clinically symptomatic within 1-3 days after PCR confirmation by parents or themselves, with 36.3% and 18.9% of paediatric cases reporting fever and cough. Also, 58.4% of paediatric cases had received at least one dose of the COVID-19 vaccine and 52.1% had received two doses of the COVID-19 vaccination. Our findings are informative for the implementation of appropriate measures to protect children from the threat of SARS-CoV-2 infection.

Unintended consequences of heavy air pollution control: efficiency losses, resource misallocation, and firm innovation in China.

Disentangling the heterogeneous effects of environmental regulations on firms' productivity and reducing the destructive effects of policies are important for achieving the goal of sustainable development. However, there is insufficient discussion of the micro-mechanisms of regulation. This study takes advantage of the good exogenous impact of China's first action plan, the Atmosphere Ten Articles, which has been formulated and implemented to solve prominent environmental problems, and constructs a difference-in-difference model based on the data of listed companies from 2012 to 2019. Results show that the policy generally has a significantly negative impact on the companies' TFP. This finding proved to be valid after a series of robustness tests, such as replacing the explained variables, eliminating the impact of penecontemporaneous policies, using propensity score matching, and applying instrumental variable methods. Due to the resource allocation mechanism, the policy undermines the companies' TFP, especially those in PM2.5 regulatory areas and state-owned companies. However, the strict emission reduction constraint instead pushes firms to innovate, and as a result, the policy's innovation mechanism promotes firms' productivity, which eventually offsets the negative effects arising from resource allocation distortions.

Effects of radiofrequency field from 5G communications on the spatial memory and emotionality in mice.

The rapid development of 5G network technology has gained much popularity as well as concerns about its adverse effects. In this study, we investigated the effects of 4.9 GHz (one of working frequencies of 5G communication) radiofrequency (RF) field on emotional behaviours and spatial memory in adult male mice. Open field test (OFT), tail suspension test (TST) and Y maze were used to evaluate anxiety, depression-like behaviour and spatial memory ability, respectively. It was found that the anxiety-like behaviour and spatial memory ability of mice did not change, but the depression-like behaviour was induced in mice after 4.9 GHz RF exposure. In addition, the number of neurons significantly reduced and the level of pyroptosis obviously increased in amygdala rather than hippocampus. These results suggested that 4.9 GHz RF exposure could induce depression-like behaviour, which might be associated with the neuronal pyroptosis in amygdala.

Abscopal effects of thoracic X-ray radiation on spermatogenesis in mice.

The study aimed to elucidate abscopal effects of thoracic X-ray irradiation on spermatogenesis in mice. Male C57BL/6 mice were randomly divided into sham group and radiation group, and subjected to thorax fractionated X-ray irradiation or sham irradiation with the total dose of 5 Gy/day for each animal for four consecutive days. After irradiation, sperm morphology was observed, and sperm number was counted under microscope, and sperm apoptosis was detected by flow cytometry. Meanwhile, testis index was calculated, testicular morphology was observed using haematoxylin-eosin (HE) staining, and testicular ultrastructure was observed under transmission electron microscopy. The permeability of blood-testis barrier (BTB) was detected by Evans Blue fluorescence colorimetry. The protein levels of Bcl-2 associated X protein (Bax), B-cell leukemia-lymphoma-2 (Bcl-2) and Cleaved caspase 3, promyelocytic leukaemia zinc finger (PLZF) and c-kit proto-oncogene (c-kit) in testes were determined by western blotting (WB). The location of apoptotic cells was confirmed by terminal deoxynucleotidyl transferase (TdT) enzymaticated dUTP nick end labelling (TUNEL) assay. The levels of tumor necrosis factor alpha (TNF-α), transforming growth factor-ß1 (TGF-ß1), interleukin 10 (IL-10) were measured by enzyme-linked immunosorbent assay (ELISA). The levels of Total superoxide dismutase (T-SOD) and malondialdehyde (MDA) were measured by the biochemical assay kit. Compared with sham group, the sperm quality of mice in radiation group showed decreased number and survival rate, along with increased abnormality and total apoptosis rate. The testis index of irradiated mice was lower, the testicular apoptosis was increased, and their testicular histology and ultrastructure was severely damaged. The permeability of BTB was increased, the level of PLZF in testis was decreased, and the level of c-kit was increased by irradiation. After irradiation, the levels of TNF-α, TGF-ß1, IL-10, T-SOD and MDA in testes were significantly changed. Taken together, abscopal effects of thoracic X-ray irradiation on spermatogenesis were obvious, which could decrease sperm quality and damage testicular morphology and increase the permeability of BTB, and a series of inflammation and oxidative stress factors were involved in the process. These findings provide novel insights into prevention and treatment for male reproductive damage induced by clinical thoracic irradiation.

Emission reduction effects of vertical environmental regulation: Capacity transfer or energy intensity reduction? Evidence from a quasi-natural experiment in China.

There is insufficient research on how to reduce the destructive effects of command-based environmental regulation through institutional design. The implementation of the National Key Monitoring Enterprises provides new evidence to assess the effects of vertical monitoring. This study integrates and matches three types of micro databases in China: industrial, pollution, and patent, and constructs firm-level panel data from 2004 to 2010. The empirical evidence shows that the policy reduces the energy use intensity of monitored enterprises by about 10.4% and sulfur dioxide emission intensity by about 23.9%. The mechanism test shows that this effect is achieved by means of energy structure optimization, process innovation, and end-of-pipe treatment, but the effect on total factor productivity is not significant. Among them, the positive impact is stronger for high-profit and emerging firms. Further, we quantify the policy-induced capacity transfer and technology spillovers from monitored enterprises to non-monitored enterprises. In terms of scale, the policy leads to a simultaneous increase in output and pollution emissions of unmonitored firms in the same industry. However, in terms of efficiency, the policy reduces the energy use intensity and pollution emission intensity of enterprises in the same industry.

Overexpression of GSTP1 promotes colorectal cancer cell proliferation, invasion and metastasis by upregulating STAT3.

BACKGROUND: The abnormal expression of glutathione S-transferase P1 (GSTP1) is associated with the progression of several tumor types. However, its role and molecular mechanism in the progression of colorectal cancer (CRC) are largely unknown. OBJECTIVES: To examine the effect of GSTP1 in CRC and determine its possible mechanisms. MATERIAL AND METHODS: In the present study, immunohistochemistry (IHC) and the quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis were used to detect the expression of GSTP1 and signal transducer and activator of transcription 3 (STAT3) in CRC tissues. Western blotting was applied to detect the expression of GSTP1 and proteins of the Janus kinase (JAK)-STAT3 pathway in different CRC cell lines. The interaction and co-localization of GSTP1 and STAT3 were detected using co-immunoprecipitation (co-IP) and immunofluorescence (IF) in the SW620 cell line. RESULTS: A positive correlation was identified between the expression of GSTP1 and STAT3 in human CRC tissues. The overexpression of GSTP1 promoted the proliferation, invasion and metastasis of CRC cells by upregulating STAT3. The GSTP1 and STAT3 can directly bind to and regulate each other. The interaction between them is regulated by the upstream gene called F-box only protein 8 (FBX8). CONCLUSIONS: The present study demonstrated that GSTP1 could enhance the expression of STAT3 to promote the proliferation, invasion and metastasis of CRC cells, which provides a potential therapeutic target for the clinical treatment of CRC.

Is there a link between inorganic polyphosphate (polyP), mitochondria, and neurodegeneration?

Mitochondrial dysfunction - including increased apoptosis, calcium and protein dyshomeostasis within the organelle, and dysfunctional bioenergetics and oxidative status - is a common, early feature in all the major neurodegenerative diseases, including Alzheimer's Disease (AD) and Parkinson's Disease (PD). However, the exact molecular mechanisms that drive the organelle to dysfunction and ultimately to failure in these conditions are still not well described. Different authors have shown that inorganic polyphosphate (polyP), an ancient and well-conserved molecule, plays a key role in the regulation of mitochondrial physiology under basal conditions. PolyP, which is present in all studied organisms, is composed of chains of orthophosphates linked together by highly energetic phosphoanhydride bonds, similar to those found in ATP. This polymer shows a ubiquitous distribution, even if a high co-localization with mitochondria has been reported. It has been proposed that polyP might be an alternative to ATP for cellular energy storage in different organisms, as well as the implication of polyP in the regulation of many of the mitochondrial processes affected in AD and PD, including protein and calcium homeostasis. Here, we conduct a comprehensive review and discussion of the bibliography available regarding the role of polyP in the mitochondrial dysfunction present in AD and PD. Taking into account the data presented in this review, we postulate that polyP could be a valid, innovative and, plausible pharmacological target against mitochondrial dysfunction in AD and PD. However, further research should be conducted to better understand the exact role of polyP in neurodegeneration, as well as the metabolism of the polymer, and the effect of different lengths of polyP on cellular and mitochondrial physiology.

Hsa_circ_001680 affects the proliferation and migration of CRC and mediates its chemoresistance by regulating BMI1 through miR-340.

BACKGROUND: Accumulating evidence indicates that circular RNAs (circRNAs) act as microRNA (miRNA) sponges to directly inhibit specific miRNAs and alter their ability to regulate gene expression at the post-transcriptional level; this mechanism is believed to occur in various cancers. However, the expression level, precise function and mechanism of circ_001680 in colorectal carcinoma (CRC) are largely unknown. METHODS: qRT-PCR was used to detect the expression of circ_001680 and miR-340 in human CRC tissues and their matched normal tissues. Bioinformatics analyses and dual-fluorescence reporter assays were used to evaluate whether circ_001680 could bind to miR-340. Circ_001680 overexpression and knockdown cell lines were constructed to investigate the proliferation and migration abilities in vivo and in vitro through function-based experiments, including CCK8, plate clone formation, transwell, and wounding healing assays. The relationships among circ_001680, miR-340 and BMI1 were investigated by bioinformatics analyses, dual-fluorescence reporter system, FISH, RIP and RNA pull down assays. Sphere forming assays and flow cytometry analyses were used to assess the effect of circ_001680 on the stemness characteristics of CRC cells. RESULTS: Circ_001680 was more highly expressed in of CRC tissue than in matched adjacent normal tissues from the same patients. Circ_001680 was observed to enhance the proliferation and migration capacity of CRC cells. Furthermore, dual-fluorescence reporter assays confirmed that circ_001680 affects the expression of BMI1 by targeting miR-340. More importantly, we also found that circ_001680 could promote the cancer stem cell (CSC) population in CRC and induce irinotecan therapeutic resistance by regulating the miR-340 target gene BMI1. CONCLUSIONS: Our results demonstrated that circ_001680 is a part of a novel strategy to induce chemotherapy resistance in CRC through BMI1 upregulation. Moreover, circ_001680 may be a promising diagnostic and prognostic marker to determine the success of irinotecan-based chemotherapy.

Removal of Rhodamine B from aqueous solution using magnetic NiFe nanoparticles.

Surface-modified magnetic nano alloy particles Ni2.33Fe were prepared using a hydrothermal method and they were utilized for removing Rhodamine B (RhB) from aqueous solution. The magnetic nanoparticles were characterized by X-ray diffraction, scanning electron microscopy, thermogravimetric analysis and Fourier transform infrared spectroscopy, which confirmed that the surface of the magnetic product with a face-centered cubic-type structure was successfully modified by sodium citrate. Kinetics studies were conducted. The pseudo-second-order kinetic model was used for fitting the kinetic data successfully. The Freundlich and Langmuir adsorption models were employed for the mathematical description of adsorption equilibrium. It was found that the adsorption isotherm can be very satisfactorily fitted by the Freundlich model.

bFGF promotes the differentiation and effectiveness of human bone marrow mesenchymal stem cells in a rotenone model for Parkinson's disease.

Previous studies have shown that bone marrow mesenchymal stem cells (BMSCs) engraftment could alleviate motor dysfunction in parkinsonian animal models, but with limited efficacy and few engrafted cells surviving. On the other side, basic fibroblast growth factor (bFGF) reportedly displays many effects including neuroprotection and promoting multipotent cells to expand and differentiate. In this study, we assessed whether a combination of bFGF and human BMSCs (HBMSCs) therapy could enhance the treatment effectiveness in Parkinson's disease (PD) rat models. Specifically, bFGF promoted HBMSCs to transdifferentiate toward neural-like lineages in vitro. In addition, HBMSCs transplantation alleviated the motor functional asymmetry, as well as prevented dopaminergic neuron loss in a PD model, while bFGF administration enhances its neurodifferentiation capacity and therapeutic effect. In conclusion, optimizing culture condition like supplementation of bFGF could significantly improve the output of HBMSCs in vitro, and HBMSCs transplantation with bFGF might represent an improved transplantation approach for PD.

Dl-3-n-butylphthalide, a natural antioxidant, protects dopamine neurons in rotenone models for Parkinson's disease.

In the absence of a cure for Parkinson's disease, development of preventive medications for this devastating disease is particularly encouraged. Dl-3-n-butylphthalide (NBP), an established natural antioxidant for clinical stroke treatment in China, can reportedly reduce beta-amyloid-induced neuronal toxicity in cultured neuronal cells, and attenuate neurodegenerative changes in aged rats. However, whether or not NBP confers neuroprotection in parkinsonian models is still unknown. In this study, we investigated the effects of NBP in rotenone models for Parkinson's diseases. In a cellular model, pretreatment with NBP enhanced cell viability by decreasing nuclear fragmentation, retaining mitochondrial membrane potential, and preventing reactive oxygen species (ROS) from generation. In a rodent model, 2-week treatment with NBP was able to ameliorate apomorphine-evoked rotations by 48% and rescue dopaminergic (DA) neurons by 30% and striatal DA terminal by 49%. Furthermore, NBP upregulated the vesicular monoamine transporter 2 gene expression in vitro and in vivo. Together, NBP protects DA neurons likely by reducing oxidative stress, offering an alternative neuroprotective medication for Parkinson's disease.

Long-term efficacy and safety of human umbilical cord mesenchymal stromal cells in rotenone-induced hemiparkinsonian rats.

Several studies have shown functional improvements, neuroprotective, and neuroregenerative effects after mesenchymal stem cells transplantation to parkinsonian animal models. However, questions remain about the safety, feasibility, and long-term efficacy of this approach. In this study, we investigated migration, therapeutic, tumorigenesis, and epileptogenic effects of human umbilical cord mesenchymal stromal cells (HUMSCs) 1 year after transplantation into rotenone-induced hemiparkinsonian rats. Our data indicated that DiI-labeled HUMSCs migrated in the lesioned hemisphere, from corpus striatum (CPu) to substantia nigra. By integrating with host cells and differentiating into NSE, GFAP, Nestin, and tyrosine hydroxylase-positive cells, HUMSCs prevented 48.4% dopamine neurons from degeneration and 56.9% dopamine terminals from loss, both correlating with improvement of apomorphine-induced rotations. The CD50 and CD97 value of pentylenetetrazol and semiquantitative immunohistochemical analysis of proliferating cell nuclear antigen (PCNA), ß-catenin, C-myc, and NF-κB expression showed no significant difference between HUMSCs transplanted and untransplanted groups, whereas the expressions of Bcl-2 and P53 in the grafted CPu were upregulated by 281% and 200% compared to ungrafted CPu. The results of this long-term study suggest that HUMSCs transplantation, 1 of the most potential treatments for Parkinson's disease, is an effective and safe approach.

Stereotaxical infusion of rotenone: a reliable rodent model for Parkinson's disease.

A clinically-related animal model of Parkinson's disease (PD) may enable the elucidation of the etiology of the disease and assist the development of medications. However, none of the current neurotoxin-based models recapitulates the main clinical features of the disease or the pathological hallmarks, such as dopamine (DA) neuron specificity of degeneration and Lewy body formation, which limits the use of these models in PD research. To overcome these limitations, we developed a rat model by stereotaxically (ST) infusing small doses of the mitochondrial complex-I inhibitor, rotenone, into two brain sites: the right ventral tegmental area and the substantia nigra. Four weeks after ST rotenone administration, tyrosine hydroxylase (TH) immunoreactivity in the infusion side decreased by 43.7%, in contrast to a 75.8% decrease observed in rats treated systemically with rotenone (SYS). The rotenone infusion also reduced the DA content, the glutathione and superoxide dismutase activities, and induced alpha-synuclein expression, when compared to the contralateral side. This ST model displays neither peripheral toxicity or mortality and has a high success rate. This rotenone-based ST model thus recapitulates the slow and specific loss of DA neurons and better mimics the clinical features of idiopathic PD, representing a reliable and more clinically-related model for PD research.