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When unbalanced faults such as single-phase voltage drop occur in the power grid, VSC-HVDC will fail or become unstable due to sudden changes in amplitude, phase, frequency, etc. of the power grid voltage. Therefore, the role of PLL in a non-ideal power grid is particularly important, but often PLL needs to make a compromise between dynamic response and system stability. Therefore, this paper proposes a free-PLL control strategy under non ideal power grid. First, according to the power transmission model of VSC-HVDC under power grid imbalance, the control command required by the inverter is given, which is determined in the environment free-PLL. Therefore, PLL is not required to retrace the phase of the grid voltage. In addition, in order to overcome the impact of the sudden change of power grid frequency on the free-PLL strategy, a frequency locking strategy is proposed in the free-PLL environment, the response time is about 1 grid cycle. Finally, in order to verify the effectiveness and correctness of the proposed strategy, the VSC-HVDC system’s active power transmission stability is guaranteed when the grid voltage encounters different degrees of single-phase sags.

The electron re-injection effect has revealed the great probability rate of photon generation due to the head-on collision between relativistic electrons and laser. We study the electron re-injection dynamics when the ultra-intense laser irradiates the near-critical-density plasma and successfully controls the photon radiation by means of the transversely tailored plasma. Starting from the relativistic corrected ponderomotive force, the critical strength of the laser field required by the refluxing effect is theoretically obtained. Then, the theoretical description of the wavefront formed by electron refluxing is given via plugging in the difference in the transverse phase velocity of the plasma wave. Simulation results display a curved surface of the refluxing electrons, which are in good agreement with the calculation results stemming from the physics model. The re-built phase space of the refluxing electrons illustrates that they gain energy mainly from the longitudinal electrostatic field on the re-injection path. Despite the energy of the refluxing electron being relatively low, it could radiate more photons via more efficient non-linear Compton scattering than the electron being accelerated in the positive direction. Furthermore, we employ a transverse density profile in the plasma and successfully achieve control of the electron re-injection effect and the properties of the resultant photons as well. Simulation results exhibit that overcritical electron beams are successively re-injected from the plasma density peaks. These backward electrons emit photons along the two maximal plasma densities as they collide with the laser pulse. Although the quality of the photons is not improved, their spatial distribution is changed, which is a big step toward manipulating light sources.

We present a novel scheme for dense electron acceleration driven by the laser irradiation of a near-critical-density plasma. The electron reflux effect in a transversely tailored plasma is particularly enhanced in the area of peak density. We observe a bubble-like distribution of re-injected electrons, which forms a strong quasistatic electromagnetic field that can accelerate electrons longitudinally while also preserving the electron transverse emittance. Simulation results demonstrate that over-dense electrons could be trapped in such an artificial bubble and accelerated to an energy of ∼500MeV. The obtained relativistic electron beam can reach a total charge of up to 0.26 nC and is well collimated with a small divergence of 17 mrad. Moreover, the wavelength of electron oscillation is noticeably reduced due to the shaking of the bubble structure in the laser field. As a result, the energy of the produced photons is substantially increased to the γ range. This new regime provides a path to generating high-charge electron beams and high-energy γ-ray sources.

Despite advances in NiCr + Cr3C2–NiCr coating improving the erosion wear resistance at low impact angles, the deterioration at medium and high impact angles has not been solved for the impeller subjecting to multi–impact angle. Herein the conflict is circumvented by combining the erosion performance of the NiCr and Cr3C2–NiCr under different impact angles and proposing a novel coating structure. First, the NiCr + Cr3C2–NiCr coating specimens with different NiCr content were prepared using the plasma spraying system. Second, the erosion rate of NiCr + Cr3C2–NiCr coatings in relation to the impact angle and the concentration of NiCr was measured by an air jet erosion test system, the microhardness was measured on the polished cross-section, and the erosion morphology was observed by SEM and analysed. Erosion behavior analysis showed that the NiCr + Cr3C2–NiCr coatings exhibited the coupling erosion wear mechanism of high toughness and high hardness, where the dominant characteristic was depending on the concentration of NiCr. Then, a tangential functional gradient coating structure was proposed by combining the excellent erosion wear resistance of ductile and brittle materials at varying impact angles, and a semi-theoretical erosion rate model considering the influence of the NiCr concentration was established based on the deformation wear theory. The erosion rate model was validated by experiments which showed the error was within 9.15%. Consequently, the erosion rate can be regulated on demand along the entire eroded surface, which significantly improves the erosion resistance of cermet at medium and high impact angles, thus prolonging the residual life of remanufactured impeller.

The differentiation of oligodendroglia from oligodendrocyte precursor cells (OPCs) to complex and extensive myelinating oligodendrocytes (OLs) is a multistep process that involves large-scale morphological changes with significant strain on the cytoskeleton. While key chromatin and transcriptional regulators of differentiation have been identified, their target genes responsible for the morphological changes occurring during OL myelination are still largely unknown. Here, we show that the regulator of focal adhesion, Tensin3 (Tns3), is a direct target gene of Olig2, Chd7, and Chd8, transcriptional regulators of OL differentiation. Tns3 is transiently upregulated and localized to cell processes of immature OLs, together with integrin-β1, a key mediator of survival at this transient stage. Constitutive Tns3 loss of function leads to reduced viability in mouse and humans, with surviving knockout mice still expressing Tns3 in oligodendroglia. Acute deletion of Tns3 in vivo, either in postnatal neural stem cells (NSCs) or in OPCs, leads to a twofold reduction in OL numbers. We find that the transient upregulation of Tns3 is required to protect differentiating OPCs and immature OLs from cell death by preventing the upregulation of p53, a key regulator of apoptosis. Altogether, our findings reveal a specific time window during which transcriptional upregulation of Tns3 in immature OLs is required for OL differentiation likely by mediating integrin-β1 survival signaling to the actin cytoskeleton as OL undergo the large morphological changes required for their terminal differentiation.

A compact electron radiography system has been designed with high gradient permanent magnet quadrupoles with 2.5 times magnification. Quasi-monoenergetic electron bunches with energies ranging from 100 to 200 MeV are generated from a laser wakefield accelerator (LWFA) acting as the electron source for the system. A matching segment composed of three quadrupoles before the objective plane creates a correlation between the position and the angle for the electrons, illuminating the observed object improved the resolution of the system. We expect electron radiography with 100-MeV ultrafast electron bunches to be widely adopted for many applications, especially considering the micron-level spatial resolution and sub-picosecond temporal resolution of the electron source from the LWFA. Since the laser system needed for generating 100–200 MeV electrons using the LWFA is roughly around 40 TW, the whole system can be effectively table-top in size, which is favorable for movable applications.

Background: Metastasis is the leading cause of death in patients with osteosarcoma. Some of these patients fail to respond to chemotherapy and die of metastasis within a short period. Therefore, it is important to identify novel biomarkers to improve the diagnosis and treatment of osteosarcoma. TRIM7 is a member of the tripartite motif (TRIM) family protein that is involved in various pathological conditions including cancer; however, its role in osteosarcoma remains elusive. Methods: Cell proliferation, invasion and migration were measured by CCK-8 and Transwell. Immunoprecipitation and mass spectrometry analysis were used to identify candidate proteins associated with TRIM7. Immunoprecipitation, immunofluorescence, pull down and ubiquitination assay were performed to examine the regulation between TRIM7 and its candidate protein. m6A modification of TRIM7 was measured by RNA immunoprecipitation. Findings: TRIM7 expression was upregulated in osteosarcoma tissues and was an independent risk factor in predicting poor prognosis. TRIM7 regulates osteosarcoma cell migration and invasion through ubiquitination of breast cancer metastasis suppressor 1 (BRMS1). Moreover, chemoresistance was readily observed in osteosarcoma cells and in patient-derived xenograft (PDX) mice with higher TRIM7 levels. Loss of TRIM7 m6A modification was observed in osteosarcoma tissues. METTL3 and YTHDF2 were the main factors involved in the aberrant m6A modification of TRIM7. Interpretation: Overall, our findings show that TRIM7 plays a key role in regulating metastasis and chemoresistance in osteosarcoma through ubiquitination of BRMS1. Funding: This work was financially supported by grants of NSFC (81001192, 81672658 and 81972521) and National Key Research Project of Science and Technology Ministry (2016YFC0106204).

To improve the surface corrosion resistance of 42CrMo4 high-strength steel used in a marine environment, this article studied the effects of hard turning on the surface integrity and corrosion resistance of 42CrMo4 high-strength steel through the single factor experimental method, namely hard turning, polarization corrosion, electrochemical impedance spectroscopy, potentiodynamic polarization curve, and salt spray tests. The results indicated that the surface integrity was modified by the hard turning, with a surface roughness lower than Ra 0.8 μm, decreased surface microhardness, fine and uniform surface microstructure, and dominant surface residual compressive stress. The hard turning process was feasible to strengthen the surface corrosion resistance of 42CrMo4 high-strength steel. The better corrosion resistance of the surface layer than that of the substrate material can be ascribed to the uniform carbides and compact microstructure. The corrosion resistance varied with cutting speeds as a result of the changed surface microhardness and residual compressive stress, varied with feed rates as a result of the changed surface roughness, and varied with cutting depths as a result of the changed surface residual compressive stress, respectively. The surface integrity with smaller surface roughness and microhardness and bigger surface residual compressive stress was beneficial for corrosion resistance.

Platycodi Radix (PR) is the root of Platycodon grandiflorum (Jacq.) A. DC., which has been used for a long time in China to treat pulmonary diseases. The present study aimed to evaluate the quality of PR samples collected from 23 regions of 11 provinces in China. Eight saponins were quantified using HPLC coupled with evaporative light scattering detection (HPLC-ELSD). The samples with the highest total contents of saponins were from southern China, such as Yunnan, Guangxi, Jiangxi, and Guangzhou. The fingerprint analysis of PR samples was conducted by HPLC-UV method. Nineteen common peaks were selected and the similarity values varied from 0.607 to 0.921. These findings indicated that the saponins contents of PR from different regions varied significantly, with PR samples from southern China having the highest contents of saponins. These comprehensive methods were successful in evaluating the quality of PR samples from northern and southern China, which will serve as a guide for the development of PR as a clinical medication.

The production of GeV electron beam with narrow energy spread and high brightness is investigated using particle-in-cell simulations. A controlled electron injection scheme and a method for phase-space manipulation in a laser plasma accelerator are found to be essential. The injection is triggered by the evolution of two copropagating laser pulses near a sharp vacuum-plasma transition. The collection volume is well confined and the injected bunch is isolated in phase space. By tuning the parameters of the laser pulses, the parameters of the injected electron bunch, such as the bunch length, energy spread, emittance and charge, can be adjusted. Manipulating the phase-space rotation with the rephasing technique, the injected electron bunch can be accelerated to GeV level while keeping relative energy spread below 0.5% and transverse emittance below 1.0 μm. The results present a very promising way to drive coherent x-ray sources.

Abstract Background Several studies have indicated that skin holds promise as a potential sample for detecting pathological α-Syn and serving as a diagnostic biomarker for α-synucleinopathies. Despite reports in Chinese PD patients, comprehensive research on skin α-Syn detection using RT-QuIC is lacking. Objective This study aimed to evaluate the diagnostic performance of skin samples using RT-QuIC from PD patients in the Chinese population. Methods Patients with sporadic PD and controls were included according to the British PD Association Brain Bank diagnostic criteria. The seeding activity of misfolded α-Syn in these skin samples was detected using the RT-QuIC assay after protein extraction. Biochemical and morphological analyses of RT-QuIC products were conducted by atomic force microscopy, transmission electron microscopy, Congo red staining, and dot blot analysis. Result 30 patients clinically diagnosed with PD and 28 controls with non-α-synucleinopathies were included in this study. 28 of 30 PD patients demonstrated positive α-Syn seeding activity by RT-QuIC assay. In contrast, no α-Syn seeding activity was detected in the 28 control samples, with an overall sensitivity and specificity of 93.3% and 100%, respectively (P

BackgroundCutaneous phosphorylated alpha-synuclein (p-α-syn) deposition is an important biomarker of idiopathic Parkinson’s disease (iPD). Recent studies have reported synucleinopathies in patients with common genetic forms of PD.ObjectiveThis study aimed to detect p-α-syn deposition characteristic in rare genetic PD patients with CHCHD2 or RAB39B mutations. Moreover, this study also aimed to describe peripheral alpha-synuclein prion-like activity in genetic PD patients, and acquire whether the cutaneous synucleinopathy characteristics of genetic PD are consistent with central neuropathologies.MethodsWe performed four skin biopsy samples from the distal leg (DL) and proximal neck (C7) of 161 participants, including four patients with CHCHD2 mutations, two patients with RAB39B mutations, 16 patients with PRKN mutations, 14 patients with LRRK2 mutations, five patients with GBA mutations, 100 iPD patients, and 20 healthy controls. We detected cutaneous synucleinopathies using immunofluorescence staining and a seeding amplification assay (SAA). A systematic literature review was also conducted, involving 64 skin biopsies and 205 autopsies of genetic PD patients with synucleinopathy.ResultsP-α-syn was deposited in the peripheral cutaneous nerves of PD patients with CHCHD2, LRRK2, or GBA mutations but not in those with RAB39B or PRKN mutations. There were no significant differences in the location or rate of α-syn-positive deposits between genetic PD and iPD patients. Peripheral cutaneous synucleinopathy appears to well represent brain synucleinopathy of genetic PD, especially autosomal dominant PD (AD-PD). Cutaneous α-synuclein SAA analysis of iPD and LRRK2 and GBA mutation patients revealed prion-like activity.ConclusionP-α-syn deposition in peripheral cutaneous nerves, detected using SAA and immunofluorescence staining, may serve as an accurate biomarker for genetic PD and iPD in the future.

Abstract Background Commonly clinically diagnosed with relapsing polychondritis (RP), vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome (VEXAS) is a recently identified autoinflammatory disease caused by UBA1 somatic mutations. The low frequency and dynamic changes challenge the accurate detection of somatic mutations. The present study monitored these mutations in Chinese patients with RP. We included 44 patients with RP. Sanger sequencing of UBA1 was performed using genomic DNA from peripheral blood. Droplet digital polymerase chain reaction (ddPCR) was performed to screen low-prevalence somatic variants. Results Multiple ddPCR detections were performed using available blood samples collected at different follow-up time points. Three male patients were UBA1 somatic mutation carriers. Sanger sequencing detected the somatic UBA1 variant c.122T > C (p.Met41Thr) in two male patients. Initial ddPCR confirmed the variant in the two patients, with allele fractions of 73.75% and 88.46%, respectively, while yielding negative results in other patients. Subsequent ddPCR detected the somatic variant (c.122T > C) with low prevalence (1.02%) in another male patient from blood samples collected at a different time point, and confirmed dynamically fractional abundance in one patient with VEXAS, with allele fractions of 73.75%, 61.28%, 65.01%, and 73.75%. Nine patients assessed by ddPCR at different time points remained negative. Conclusion We report UBA1 variants in patients with RP in the Chinese population for the first time. Multiple ddPCR detections from samples collected at different time points can enhance sensitivity and should be considered for patients with initial negative ddPCR results.

This paper studied the flexural behavior of bridge deck link slabs made with polyvinyl alcohol–strain-hardening cementitious composites (PVA-SHCC). The tensile and flexural properties of the self-compacting PVA-SHCC with four volume fractions, i.e., 0%, 1%, 1.5%, and 2%, were evaluated first. Next, using the similarity theory, composite models with a geometric similarity ratio of 1:5 were designed to represent the bridge deck with the link slabs. The models considered three materials for link slabs, including concrete, cement mortar, and self-compacting PVA-SHCC, and two different curing ages at 7 and 56 days. Bending tests were performed to investigate the flexural behavior of the models. Based on the fractal theory, the cracking characteristics of the models with different types of link slabs were compared, and the relationship between fractal dimensions and the flexural behavior of the models was studied. Numerical models were built to correlate with the results from the bending tests. It was illustrated that the flexural behavior of the self-compacting PVA-SHCC link slab is better than that of concrete and cement mortar link slabs, where the crack initiation and propagation can be postponed. The results can provide theoretical support and design guidance for the self-compacting PVA-SHCC bridge deck.

Over 50 genetic human disorders are attributed to the irregular expansion of microsatellites. These expanded microsatellite sequences can experience bidirectional transcription, leading to new reading frames. Beyond the standard AUG initiation or adjacent start codons, they are translated into proteins characterized by disease-causing amino acid repeats through repeat-associated non-AUG translation. Despite its significance, there's a discernible gap in comprehensive and objective articles on RAN translation. This study endeavors to evaluate and delineate the contemporary landscape and progress of RAN translation research via a bibliometric analysis. We sourced literature on RAN translation from the Web of Science Core Collection. Utilizing two bibliometric analysis tools, CiteSpace and VOSviewer, we gauged individual impacts and interactions by examining annual publications, journals, co-cited journals, countries/regions, institutions, authors, and co-cited authors. Following this, we assessed the co-occurrence and bursts of keywords and co-cited references to pinpoint research hotspots and trending in RAN translation. Between 2011 and 2022, 1317 authors across 359 institutions from 34 countries/regions contributed to 250 publications on RAN translation, spread across 118 academic journals. This article presents a systematic, objective, and comprehensive analysis of the current literature on RAN translation. Our findings emphasize that mechanisms related to C9orf72 ALS/FTD are pivotal topics in the realm of RAN translation, with cellular stress and the utilization of small molecule marking the trending research areas.

Sodium p-perfluorous nonenoxybenzenesulfonate (OBS) is a novel alternative to perfluorooctane sulfonate (PFOS), with environmental health risks largely unknown. The present study aims to unravel the adipogenesis effects and underlying molecular initiating events of OBS, which are crucial for understanding and predicting its adverse outcome. In undifferentiated human mesenchymal stem cells (hMSCs), exposure to 1–100 nM of OBS for 7 days stimulated reactive oxygen species production. In the subsequent multipotent differentiation, hMSCs favored adipogenesis and repressed osteogenesis. The point of departure (PoD) for cellular responses of OBS was 38.85 nM, higher than PFOS (0.39 nM). Notably, OBS/PFOS co-exposure inhibited osteogenesis and synergistically promoted adipogenesis. Consistently, the expression of adipogenic marker genes was up-regulated, while that of osteogenic marker genes was down-regulated. The decreased adiponectin and elevated tumor necrosis factor α (TNFα) secretion were observed in differentiated cells exposed to the mixture of OBS and PFOS. The co-treatment of a peroxisome proliferator-activated receptor γ (PPARγ) antagonist alleviated the adipogenic effects of PFOS and its combination with OBS. Moreover, OBS/PFOS co-exposure induced peroxisome PPARγ activation in reporter gene assays, and increased formation of PPARγ - retinoid X receptor α (RXRα) heterodimers measured by co-immunoprecipitation assays. Molecular docking showed interaction energy of OBS (-20.7 kcal/mol) with intact PPARγ-RXRα complex was lower than that of PFOS (-25.9 kcal/mol). Overall, single OBS exhibited lower potency in inducing adipogenesis but is comparable to PFOS in repressing osteogenesis, whereas OBS/PFOS co-exposure increases interaction with PPARγ-RXRα heterodimers, resulting in the synergistic activation of PPARγ, ultimately enhancing adipogenesis at the expense of osteogenic differentiation. The results indicate the potential health risks of increased obesity and decreased bone density caused by OBS and its co-exposure with PFOS, as well as other perfluorinated alkylated substances mixtures.

Abstract Nasal swabs are non-invasive testing methods for detecting diseases by collecting samples from the nasal cavity or nasopharynx. Dysosmia is regarded as an early sign of coronavirus disease 2019 (COVID-19), and nasal swabs are the gold standard for the detection. By nasal swabs, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acids can be cyclically amplified and detected using real-time reverse transcriptase-polymerase chain reaction after sampling. Similarly, olfactory dysfunction precedes the onset of typical clinical manifestations by several years in prion diseases and other neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. In neurodegenerative diseases, nasal swab tests are currently being explored using seed amplification assay (SAA) of pathogenic misfolded proteins, such as prion, α-synuclein, and tau. These misfolded proteins can serve as templates for the conformational change of other copies from the native form into the same misfolded form in a prion-like manner. SAA for misfolded prion-like proteins from nasal swab extracts has been developed, conceptually analogous to PCR, showing high sensitivity and specificity for molecular diagnosis of degenerative diseases even in the prodromal stage. Cyclic amplification assay of nasal swab extracts is an attractive and feasible method for accurate and non-invasive detection of trace amount of pathogenic substances for screening and diagnosis of neurodegenerative disease. Graphical Abstract

Objectives ‒ This multicenter retrospective study aimed to compare the effects of HES and gelatin (GEL) on the risk of post-OLT AKI. Method ‒ A total of 1,672 patients undergoing OLT were enrolled from major transplant centers in China between 2005 and 2013. These patients were divided into three groups: GEL, hydroxyethyl starch (HES), and GEL + HES group. Results ‒ There was no significant difference in the incidence of post-OLT AKI among the GEL, HES, and GEL + HES groups. The GEL + HES group had a lower incidence of stage II post-OLT AKI than the other two groups. Compared with patients receiving GEL, patients receiving HES did not harbor an increased risk of AKI. Our results showed that MELD score (adjusted odds ratio [OR], 1.579; 95% confidence interval [CI], 1.123–2.219; P = 0.009) and preoperative anemia (adjusted OR, 1.533; 95% CI, 1.212–1.939; P < 0.001) were independent risk factors for post-OLT AKI, and normal preoperative Scr level (vs abnormal; adjusted OR, 0.402; 95% CI, 0.222–0.729; P = 0.003) was independent protective factors for post-OLT AKI. Conclusion ‒ This large-scale multicenter retrospective study found that the intraoperative use of HES did not increase the overall incidence of post-OLT AKI in patients when compared with GEL, and whether to increase the risk of post-OLT AKI needs to be further explored. [ABSTRACT FROM AUTHOR]

This work intends to get a better understanding of cluster formation in supersonic nozzles of different geometries. The throat diameters d are within 0.26 mm≤d≤0.62 mm, the half-opening-angle α within 4.2°≤α≤11.3°, and the length L of the conical section is 17.5 mm (eight nozzles) or 12 mm (two nozzles). Thus the so-called “equivalent sonic-nozzle diameter deq” for these conical nozzle geometries, defined by deq=0.74 d/tan α (for monatomic gases), is in the range of 1.59 mm≤deq≤5.21 mm. Source temperature for the clustering experiments was T0=298 K, and the backing pressure P0 was between 0.5 and 30 bars. The (average) cluster sizes observed for these conical nozzles deviate from the predictions of the simple stream-tube-model. These deviations are accounted for by introducing the so-called “effective equivalent sonic-nozzle diameter deq*,” defined as the product of the equivalent sonic-nozzle diameter deq and a new parameter δ, deq*=δdeq. The parameter δ serves to modify the equivalent diameters deq of the conical nozzles, which are applied in the idealized cases where the gas flows are suggested to be formed through free jet expansion. Then, δ represents the deviation of the performance in cluster formation of the practical conical nozzles from those predicted based on the idealized picture. The experimental results show that the values of δ can be described by an empirical formula, depending on the gas backing pressure P0 and the parameter deq of the conical nozzles. The degradation of the performance of the present conical nozzles was found with the increase in P0 and the larger deq. It was revealed that δ is inversely proportional to a fractional power (∼0.5–0.6) of the molecular density nmol in the gas flows under the present experimental conditions. The boundary layers effects are considered to be mainly responsible for the restriction of the performance of the conical nozzles in cluster formation. [ABSTRACT FROM AUTHOR]

Spinocerebellar ataxia type 3 (SCA3), also known as Machado–Joseph disease, is the most common dominantly inherited ataxia. SCA3 is caused by a CAG repeat expansion in the ATXN3 gene that encodes an expanded tract of polyglutamine in the disease protein ataxin-3 (ATXN3). As a deubiquitinating enzyme, ATXN3 regulates numerous cellular processes including proteasome- and autophagy-mediated protein degradation. In SCA3 disease brain, polyQ-expanded ATXN3 accumulates with other cellular constituents, including ubiquitin (Ub)-modified proteins, in select areas like the cerebellum and the brainstem, but whether pathogenic ATXN3 affects the abundance of ubiquitinated species is unknown. Here, in mouse and cellular models of SCA3, we investigated whether elimination of murine Atxn3 or expression of wild-type or polyQ-expanded human ATXN3 alters soluble levels of overall ubiquitination, as well as K48-linked (K48-Ub) and K63-linked (K63-Ub) chains. Levels of ubiquitination were assessed in the cerebellum and brainstem of 7- and 47-week-old Atxn3 knockout and SCA3 transgenic mice, and also in relevant mouse and human cell lines. In older mice, we observed that wild-type ATXN3 impacts the cerebellar levels of K48-Ub proteins. In contrast, pathogenic ATXN3 leads to decreased brainstem abundance of K48-Ub species in younger mice and changes in both cerebellar and brainstem K63-Ub levels in an age-dependent manner: younger SCA3 mice have higher levels of K63-Ub while older mice have lower levels of K63-Ub compared to controls. Human SCA3 neuronal progenitor cells also show a relative increase in K63-Ub proteins upon autophagy inhibition. We conclude that wild-type and mutant ATXN3 differentially impact K48-Ub- and K63-Ub-modified proteins in the brain in a region- and age-dependent manner.

As the primary molecular target, there is still a gap between the peroxisome proliferator-activated receptors (PPARs) regulation and the adverse health effects caused by per- and polyfluoroalkyl substances (PFASs). The effects of PFASs on cellular differentiation regulated by PPARs is likely significant given the association of PFASs exposure with obesity and decreased bone density. Human mesenchymal stem cells (hMSCs) were used as an in vitro model to assess the roles of PPAR subtypes in the multipotent differentiation of hMSCs affected by perfluorooctanesulfonate (PFOS), perfluorooctanoic acid (PFOA) and their replacement compounds. PFASs increased the expression of three PPAR subtypes in proliferating and differentiating hMSCs. Meanwhile, PFOS and PFOA decreased osteogenesis, enhanced adipogenesis, and increased bone turnover in hMSCs. Similarly, PFOA alternatives, hexafluoropropylene oxide dimer acid (HFPO-DA) and hexafluoropropylene oxide trimer acid (HFPO-TA), exhibited similar or even higher potency in affecting stem cell differentiation compared with PFOA. Perfluorohexanesulfonate (PFHxS) inhibited osteogenesis with comparable potency to PFOS. In contrast, 6:2 chlorinated poly-fluoroalkyl ether sulfonate (6:2Cl-PFESA) enhanced osteogenesis. PPARβ expression is significantly positively correlated with osteogenesis and osteoprotegerin (OPG) secretion in 6:2Cl-PFESA treated cells. shRNA knockdown of PPARβ remarkably reversed the osteogenic effects of 6:2Cl-PFESA and enhanced the adipogenic effects of the six chemicals. The results suggested that the adverse effects and relative potency of PFASs on the multipotent differentiation of hMSCs were dependent on the integrated action of the three PPAR subtypes, which facilitates a better understanding of the molecular initiating events of PFASs. The present study may well explain the mechanism of the decreased bone density and increased obesity incidence among those exposed to legacy PFASs, and indicates the necessity of further health risk assessment for the alternatives.

The accumulation and deposition of misfolded α-synuclein (α-Syn) aggregates in the brain is the central event in the pathogenesis of α-synucleinopathies, including Parkinson’s disease, dementia with Lewy bodies, and multiple-system atrophy. Currently, the diagnosis of these diseases mainly relies on the recognition of advanced clinical manifestations. Differential diagnosis among the various α-synucleinopathies subtypes remains challenging. Misfolded α-Syn can template its native counterpart into the same misfolded one within or between cells, behaving as a prion-like seeding. Protein-misfolding cyclic amplification and real-time quaking-induced conversion are ultrasensitive protein amplification assays initially used for the detection of prion diseases. Both assays showed high sensitivity and specificity in detection of α-synucleinopathies even in the pre-clinical stage recently. Herein, we collectively reviewed the prion-like properties of α-Syn and critically assessed the detection techniques of α-Syn-seeding activity. The progress of test tissues, which tend to be less invasive, is presented, particularly nasal swab, which is now widely known owing to the global fight against coronavirus disease 2019. We highlight the clinical application of α-Syn seeding in early and non-invasive diagnosis. Moreover, some promising therapeutic perspectives and clinical trials targeting α-Syn-seeding mechanisms are presented.

A recent large-scale European-originated genome-wide association study identified 38 novel independent risk signals in 37 loci for Parkinson's disease (PD). However, whether these new loci are associated with PD in Asian populations remains elusive. The present study aimed to explore the relationship between the 12 most relevant loci with larger absolute values for these new risk loci and PD in the Chinese Han population. We performed a case-control study including 527 PD patients and 435 healthy controls. In the allele model, it was found that rs10748818/GBF1 was associated with PD in the Chinese Han population [p = 0.035, odds ratio (OR) 1.221, 95% confidence interval (CI) 1.014–1.472

Despite the position of farmer cooperatives in markets and their social capital based characteristics, neither the definition nor the role of social capital in farmer cooperatives has been broadly investigated. Thus, this study seeks to develop a framework for defining and clarifying various aspects of social capital and examines the effects of social capital on members' participation in collective activities and on the economic performance of farmer cooperatives. Social capital is indicated in terms of three dimensions, i.e., the external, relational, and cognitive dimensions. A statistical model is applied to a database consisting of 147 farmer cooperatives in China's Zhejiang province. The results demonstrate a positive relationship between certain dimensions of social capital and members' participation in training and general meetings. In addition, each dimension of social capital has a significant and positive impact on the economic performance of cooperatives. [ABSTRACT FROM AUTHOR]

Parkinson’s disease (PD) is the second most common neurodegenerative disease. The molecular mechanisms of PD at the cellular level involve oxidative stress, mitochondrial dysfunction, autophagy, axonal transport, and neuroinflammation. Induced pluripotent stem cells (iPSCs) with patient-specific genetic background are capable of directed differentiation into dopaminergic neurons. Cell models based on iPSCs are powerful tools for studying the molecular mechanisms of PD. The iPSCs used for PD studies were mainly from patients carrying mutations in synuclein alpha (SNCA), leucine-rich repeat kinase 2 (LRRK2), PTEN-induced putative kinase 1 (PINK1), parkin RBR E3 ubiquitin protein ligase (PARK2), cytoplasmic protein sorting 35 (VPS35), and variants in glucosidase beta acid (GBA). In this review, we summarized the advances in molecular mechanisms of Parkinson’s disease using iPSC models.

An experimental investigation on the interaction of an ultraintense femtosecond laser pulse at the intensity of 2×1017 W/cm2 (60 fs, 120 mJ at 800 nm) with clusters in a supersonic jet of deuterated methane gas has shown the generation of energetic deuterons and nuclear fusion events. The deuteron density and the average size of the clusters in the gas jet, as well as the fusion neutron yields under different backing pressures were measured simultaneously as a function of the time delays of the laser pulses with respect to the puffing of the gas jet. The results demonstrate that during the development of the gas jet expanding through a conical nozzle, the clusters grew up with time, and the average size of the clusters reached the maximum when the molecular density in the jet started to drop. The fusion neutron yields were found to increase with the larger average cluster size and the higher deuteron density, in accordance with the theoretical prediction. Experimental data indicate the existence of a ∼1 ms steady region in which the fusion neutron yields have reached the maximum of 2.0×105 per shot at the backing pressure of 74 bars. Consequently, an efficiency of 1.6×106 neutrons per joule of incident laser energy was realized. [ABSTRACT FROM AUTHOR]

The experimental results of low pressure supersonic molecular beam injection (SMBI) fuelling on the HL-2A closed divertor indicate that during the period of pulsed SMBI the power density convected at the target plate surfaces was 0.4 times of that before or after the beam injection. An empirical scaling law used for the SMBI penetration depth for the HL-2A plasma was obtained. The cluster jet injection (CJI) is a new fuelling method which is based on and developed from the experiments of SMBI in the HL-1M tokamak. The hydrogen clusters are produced at liquid nitrogen temperature in a supersonic adiabatic expansion of moderate backing pressure gases into vacuum through a Laval nozzle and are measured by Rayleigh scattering. The measurement results have shown that the averaged cluster size of as large as hundreds of atoms was found at the backing pressures of more than 0.1 MPa. Multifold diagnostics gave coincidental evidence that when there was hydrogen CJI in the HL-2A plasma, a great deal of particles from the jet were deposited at a terminal area rather than uniformly ablated along the injecting path. SMB with clusters, which are like micro-pellets, will be of benefit for deeper fuelling, and its injection behaviour was somewhat similar to that of pellet injection. Both the particle penetration depth and the fuelling efficiency of the CJI were distinctly better than that of the normal SMBI under similar discharge operation. During hydrogen CJI or high-pressure SMBI, a combination of collision and radiative stopping forced the runaway electrons to cool down to thermal velocity due to such a massive fuelling. [ABSTRACT FROM AUTHOR]

The dependence of the maximum and average energies of protons, which were produced in the interaction of an intense laser pulse (?1 × 1016W cm?2, 65 fs) with hydrogen clusters in a gas jet backed up to 80 bar at liquid nitrogen temperature (?80 K), on the backing pressure has been studied. The general trend of the proton energy dependence on the square of the average cluster radius, which is determined by a calibrated Rayleigh scattering measurement, is similar to that described by theory under the single size approximation. Calculations are made to fit the experimental results under a simplified model by taking into account both a log-normal cluster size distribution and the laser intensity attenuation in the interaction volume. A very good agreement between the experimental proton energy spectra and the calculations is obtained in the high-energy part of the proton energy distributions, but a discrepancy of the fits is revealed in the low-energy part at higher backing pressures which are associated with denser flows. A possible mechanism which would be responsible for this discrepancy is discussed. Finally, from the fits, a variation of the cluster size distributions was revealed to be dependent on the gas backing pressure as well as on the evolving time of the gas flow of clusters. [ABSTRACT FROM AUTHOR]

Laser wakefield acceleration of electrons well beyond 1 GeV and optical guiding of ultraintense laser pulses of peak powers up to 160 TW over a 4-cm long ablative capillary discharge plasma channel were experimentally demonstrated. Electron beams, with energies up to 1.8 GeV, were generated by using the 130 TW, 55 fs driving laser pulses. A comparison of oxygen-containing acrylic resin (C:O:H = 4:2:7) capillary and no oxygen-containing polyethylene (C:O:H = 1:0:2) capillary measurements suggests that the injection of electron into the laser wakefield is assisted by the ionization of oxygen K-shell electrons. [ABSTRACT FROM AUTHOR]

A gas sensor made from graphene vertical field effect transistor (VGr-FET) has been fabricated using graphene as the source electrode, C60 thin film as the semiconductor layer and aluminum thin film as the drain electrode. The on/off ratio of transistor gated by bottom electrode with ionic liquid gel as dielectric layer is derived to be 103 from measured source–drain current Ids. The apparent energy barrier height between the graphene and polycrystalline fullerene was calculated from the model of heterojunction diode I–V response curves. The barrier height φBH was altered by the gating potential vertically applied on graphene sheet, resulting the large on/off ratio of the transistor. The effect of surface adsorption of water vapor, oxygen, ammonia and isoprene gas phase molecules on the Ids was measured. The lower limit of detection (LOD) for ammonia (86 ppb) than that of isoprene (420 ppb) is attributed to the donor nature of ammonia contact with p-type graphene, and the adsorbed donor leads to a corresponding positive gating effect to the VGr-FET. This facile, low cost and quick responsive device shows promise for early diagnose of severe human respiratory diseases. [ABSTRACT FROM AUTHOR]

The nonlinear vibration of a rotor excited by transverse electromagnetic and oil-film forces is presented in this paper. The rotor-bearing system is modeled as a continuum beam which is loaded by a distributed electromagnetic load and is supported by two oil-film bearings. The governing equation of motion is derived and discretized as a group of ordinary differential equations using the Galerkin's method. The stability of the equilibrium of the rotor is analyzed with the Routh-Hurwitz criterion and the occurrence of the Andronov-Hopf bifurcation is pointed out. The approximate solution of periodic motion is obtained using the averaging method. The stability of steady response is analyzed and the amplitude-frequency curve of primary resonance is illustrated. The Runge-Kutta method is adopted to numerically solve transient response of the rotor-bearing system. Comparisons are made to present influences of electromagnetic load, oil-film force and both of them on the nonlinear vibration response. Bifurcation diagrams of the transverse motion versus rotation speed, electromagnetic parameter and bearing parameters are provided to show periodic motion, quasi-periodic motion and period-doubling bifurcations. Diagrams of time history, shaft orbit, the Poincaré section and fast Fourier transformation of the transverse vibration are presented for further understanding of the rotor response.

Multiple system atrophy (MSA) is a neurodegenerative disease, and its pathological hallmark is the accumulation of α-synuclein proteins. Homocysteine (Hcy) is an intermediate amino acid generated during the metabolism of methionine. Hcy may contribute to the pathogenesis of neurodegenerative disorders. Vitamin B12 and folate are cofactors necessary for the methylation of homocysteine.This study compared the levels of serum Hcy, vitamin B12 and folate in patients with MSA with those in healthy people to reveal the possible association between MSA and plasma levels of Hcy, vitamin B12 and folate. We enrolled 161 patients with MSA and 161 healthy people in this study. The association between MSA and the levels of Hcy, vitamin B12 and folate were analyzed using binary logistic regression.The mean level of Hcy in patients with MSA was significantly higher than that in healthy controls (16.23 ± 8.09 umol/l vs 14.04 ± 4.25 umol/l, p < 0.05). After adjusting for age, sex and medical history, the odds ratio for Hcy was 1.07 (95% CI = 1.01-1.13, p < 0.05) for patients with MSA. Vitamin B12 and folate levels were not significantly different between patients with MSA and controls.Our data suggest that higher levels of Hcy may be associated with an increased risk for MSA.

With the development of laser technology, laser-driven proton acceleration provides a new method for proton tumor therapy. However, it has not been applied in practice because of the wide and decreasing energy spectrum of laser-accelerated proton beams. In this paper, we propose an analytical model to reconstruct the spread-out Bragg peak (SOBP) using laser-accelerated proton beams. Firstly, we present a modified weighting formula for protons of different energies. Secondly, a theoretical model for the reconstruction of SOBPs with laser-accelerated proton beams has been built. It can quickly calculate the number of laser shots needed for each energy interval of the laser-accelerated protons. Finally, we show the 2D reconstruction results of SOBPs for laser-accelerated proton beams and the ideal situation. The final results show that our analytical model can give an SOBP reconstruction scheme that can be used for actual tumor therapy. [ABSTRACT FROM AUTHOR]

By irradiating a flat A1 target with femtosecond laser pulses at moderate intensities of ~1017 W/cm>2, we obtained stable collimated quasimonoenergetic electrons in the specular direction but deviated somewhat toward the target normal. An associated local minimum located on the other side of the specular direction seems to indicate that the peak actually results from the deflection of the collimated electrons from their initial ejection direction. We have proposed a two-step model in which some laser-accelerated electrons are able to leave the plasma in a narrow phase-locked window of the moving wave interference pattern, and are then steered toward the target normal by the ponderomotive force of the interference field. The periodic repetition of the electron emission leads to a pulse train of collimated quasimonoenergetic electrons with subcycle duration. [ABSTRACT FROM AUTHOR]