Extended haplotype with rs41524547-G defines the ancestral origin of SCA10.

Spinocerebellar ataxia type 10 (SCA10) is a rare autosomal dominant ataxia caused by a large expansion of the (ATTCT)n repeat in ATXN10. SCA10 was described in Native American and Asian individuals which prompted a search for an expanded haplotype to confirm a common ancestral origin for the expansion event. All patients with SCA10 expansions in our cohort share a single haplotype defined at the 5'-end by the minor allele of rs41524547, located ~35 kb upstream of the SCA10 expansion. Intriguingly, rs41524547 is located within the miRNA gene, MIR4762, within its DROSHA cleavage site and just outside the seed sequence for mir4792-5p. The world-wide frequency of rs41524547-G is less than 5% and found almost exclusively in the Americas and East Asia-a geographic distribution that mirrors reported SCA10 cases. We identified rs41524547-G(+) DNA from the 1000 Genomes/International Genome Sample Resource and our own general population samples and identified SCA10 repeat expansions in up to 25% of these samples. The reduced penetrance of these SCA10 expansions may be explained by a young (pre-onset) age at sample collection, a small repeat size, purity of repeat units, or the disruption of miR4762-5p function. We conclude that rs41524547-G is the most robust at-risk SNP allele for SCA10, is useful for screening of SCA10 expansions in population genetics studies and provides the most compelling evidence to date for a single, prehistoric origin of SCA10 expansions sometime prior to or during the migration of individuals across the Bering Land Bridge into the Americas.

Preparation of high-affinity and high-specificity monoclonal antibody and development of ultra-sensitive immunoassay for the detection of 1-aminohydantoin, the metabolite of nitrofurantoin.

1-Aminohydantoin (AHD), the residual marker of nitrofurantoin, is usually detected after derivatisation using the derivatisation reagent 2-nitrobenzaldehyde. Avoiding the antibody recognition of the derivatisation reagent is essential for the accurate detection of AHD residues. In this paper, a novel hapten called hapten D was designed, and then, a monoclonal antibody that did not recognise 2-nitrobenzaldehyde was prepared based on this novel hapten. An ultra-sensitive indirect competitive enzyme linked-immunosorbent assay (icELISA) was established under optimal conditions. The 50% inhibition concentration and limit of detection of AHD were 0.056 and 0.0060 ng/mL, respectively, which improved the sensitivity by 9-37-fold compared with the previously reported icELISA methods. The average recovery rates were 88.1%-97.3%, and the coefficient of variation was <8.6%. The accuracy and reliability of the icELISA were verified using liquid chromatography-tandem mass spectrometry. These results demonstrated that the developed icELISA is a useful and reliable tool.

A novel bellidifolin intervention mitigates nonalcoholic fatty liver disease-like changes induced by bisphenol F.

As a potential endocrine-disrupting chemical, bisphenol F (BPF) may cause nonalcoholic fatty liver disease (NAFLD)-like changes, but the mechanisms underpinning its pathogenesis as well as the intervention strategies remain poorly understood. Using the electron microscopy technology, along with LipidTOX Deep Red neutral and Bodipy 493/503 staining assays, we observed that BPF treatment elicited a striking accumulation of lipid droplets in HepG2 cells, accompanied by an increased total level of triglycerides. At the molecular level, the lipogenesis-associated mRNAs and proteins, including acetyl-CoA carboxylase, fatty acid synthase, stearoyl-CoA desaturase-1, peroxisome proliferator-activated receptor gamma, and CCAAT-enhancer-binding proteins, increased significantly via the AMP-activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR) signaling regulation in both in vitro and in vivo studies. Furthermore, the immunofluorescence results also showed the robust lipogenesis induced by BPF, evident in its ability to promote the translocation of sterol regulatory element-binding protein-1c from the cytoplasm to the nuclei. To investigate the intervention strategies for BPF-induced NAFLD-like changes, we demonstrated that bellidifolin, isolated and purified from Swertia chirayita, significantly attenuated BPF-induced lipid droplet deposition in HepG2 cell and NAFLD-like changes in mice by blocking the expression of lipogenesis-associated proteins. Therefore, the present study elucidates the mechanisms underlying BPF-induced lipid accumulation in HepG2 cells, while also highlighting the potential of bellidifolin to mitigate BPF-induced NAFLD-like changes.

Bisphenol F exposure induces depression-like changes: Roles of the kynurenine metabolic pathway along the "liver-brain" axis.

Bisphenol F (BPF), one of the major alternatives of Bisphenol A (BPA), is becoming extensively used in industrial production with great harm to human beings and environment. Recent studies have revealed that environmental exposure is crucial to the initiation and development of depression. Thereby, the aim the present study is to ascertain the correlationship between the BPF exposure and depression occurrence. In the current study, BPF strikingly triggered depression-like changes in mice through the sucrose preference test (SPT), tail suspension test (TST) and forced swim test (FST), accompanied by the perturbation of the kynurenine (KYN) metabolic pathway along the "liver-brain" axis. Mechanistically, the neurotransmitters from the tryptophan metabolic pathway were converted to the toxic KYN pathway after BPF treatment. With the ELISA assay, it revealed that the toxic KYN metabolites, including KYN and 3-hydroxykynurenine (3-HK), were strikingly increased in the mouse brains which was ascribed to the enhanced expression of the rate-limiting enzymes Indoleamine 2,3-dioxygenase (IDO1) and Kynurenine 3-monooxygenase (KMO) respectively. Interestingly, the increased brain KYN induced by BPF was also validated partially from the periphery, since the ELISA and western blotting results indicated the significantly increased KYN in the serum and L-type amino acid transporter 1 (LAT1) in the brain, the key transporter responsible for KYN and 3-HK crossing the blood-brain barrier. Intriguingly, the liver-derived KYN metabolic pathway was the important source of the peripheral KYN and 3-HK, as BPF substantially enhanced hepatic IDO1, Tryptophan, 2, 3-dioxygenase (TDO2), and KMO levels indicated by western blotting. This study is the first to delineate previously unrecognized BPF-induced depression by regulating the KYN metabolic pathway along the "liver-brain" axis; therefore, targeting LAT1 or hepatic KYN signaling may provide a potentially unique therapeutic intervention in BPF-induced depression.

Pulse pressure level after acute ischemic stroke is associated with early neurological deterioration.

Early neurological deterioration (END) is an unfavorable outcome of acute ischemic stroke and is associated with poor prognosis. Blood pressure variability has been suggested to be involved in the development of END. Therefore, the present study investigated the association between blood pressure variability and the development of END. In the present prospective observational study, 286 patients who developed acute ischemic stroke and then hospitalized within 24 h of stroke onset were recruited. Blood pressure parameters (systolic blood pressure, diastolic blood pressure and pulse pressure) were monitored using a 24 h ambulatory sphygmomanometer within 72 h of ischemic onset. Clinical characteristics were also recorded. Multivariate logistic regression analysis was used to analyze the possible relationship between blood pressure parameters and END after adjustment for confounders. Of the 286 patients in the present study, 64 (22.3%) developed END. Pulse pressure variables, including the mean of 24-h pulse pressure (24-h PPMEAN) and the mean of daytime pulse pressure (Day PPMEAN), were found to be higher in the END group compared with those in the non-END group (P<0.05). Multivariate logistic regression analysis revealed that the blood pressure parameters 24-h PPMEAN [odds ratio (OR), 1.08; 95% CI, 1.01-1.16; P=0.02) and Day PPMEAN (OR, 1.20; 95% CI, 1.011-1.45; P=0.04) were significantly associated with END. These findings suggest that the pulse pressure level fluctuations during the acute stage of ischemic stroke can serve important roles in the development of END, which worsens outcomes after stroke.

Targeting CD38/ ADP-ribosyl cyclase as a novel therapeutic strategy for identification of three potent agonists for leukopenia treatment.

Leukopenia is the most common side effect of chemotherapy and radiotherapy. It potentially deteriorates into a life-threatening complication in cancer patients. Despite several agents being approved for clinical administration, there are still high incidences of pathogen-related disease due to a lack of functional immune cells. ADP-ribosyl cyclase of CD38 displays a regulatory effect on leukopoiesis and the immune system. To explore whether the ADP-ribosyl cyclase was a potential therapeutic target of leukopenia. We established a drug screening model based on an ADP-ribosyl cyclase-based pharmacophore generation algorithm and discovered three novel ADP-ribosyl cyclase agonists: ziyuglycoside II (ZGSII), brevifolincarboxylic acid (BA), and 3,4-dihydroxy-5-methoxybenzoic acid (DMA). Then, in vitro experiments demonstrated that these three natural compounds significantly promoted myeloid differentiation and antibacterial activity in NB4 cells. In vivo, experiments confirmed that the compounds also stimulated the recovery of leukocytes in irradiation-induced mice and zebrafish. The mechanism was investigated by network pharmacology, and the top 12 biological processes and the top 20 signaling pathways were obtained by intersecting target genes among ZGSII, BA, DMA, and leukopenia. The potential signaling molecules involved were further explored through experiments. Finally, the ADP-ribosyl cyclase agonists (ZGSII, BA, and DMA) has been found to regenerate microbicidal myeloid cells to effectively ameliorate leukopenia-associated infection by activating CD38/ADP-ribosyl cyclase-Ca2+-NFAT. In summary, this study constructs a drug screening model to discover active compounds against leukopenia, reveals the critical roles of ADP-ribosyl cyclase in promoting myeloid differentiation and the immune response, and provides a promising strategy for the treatment of radiation-induced leukopenia.

Monospecific and ultrasensitive detection of ofloxacin: A computational chemistry-assisted hapten screening strategy and analysis of molecular recognition mechanism.

Contamination in food and the environment with fluoroquinolones (FQs) has become a serious threat to the global ecological balance and public health safety. Ofloxacin (OFL) is one of the most widely utilized sterilization agents in FQs. In the process of monitoring OFL, broad-spectrum monoclonal antibodies (mAb) cannot meet the demand for monospecific detection. Here, a computational chemistry-assisted hapten screening strategy was proposed in this study. Differences in the properties of antigenic epitopes were precisely extracted through a comprehensive comparative study of 16 common FQs molecules and a monospecific and ultrasensitive mAb-3B4 for OFL was successfully prepared. The screened fleroxacin (FLE) hapten was applied in a heterologous competition strategy resulting in a 20-fold improvement in the half inhibitory concentration (IC50) of mAb-3B4 to 0.0375 µg L-1 and cross-reacted only with marbofloxacin (MAR) in regulated FQs. In addition, a single-chain variable fragment (scFv) for OFL was constructed for the first time with an IC50 of 0.378 µg L-1. Molecular recognition mechanism studies validated the reliability of this strategy and revealed the key amino acid sites responsible for OFL specificity and sensitivity. Finally, ic-ELISA and GICA were established for OFL in real samples. This work provides new ideas for the preparation of monospecific mAb and improves the monitoring system of FQs.

Physicochemical Properties and Hypolipidemic Activity of Dietary Fiber from Rice Bran Meal Obtained by Three Oil-Production Methods.

This study investigated the effects of three oil production methods on the physicochemical properties of dietary fiber from rice bran flour, and the hypolipidemic effects of the dietary fibers were investigated in vitro and in vivo. The particle size results showed that the organic-solvent-impregnated rice bran meal dietary fiber (N-RBDF) had the smallest average particle size and the aqueous enzymatic rice bran meal dietary fiber (E-RBDF) had the narrowest particle size distribution. Scanning electron microscopy (SEM) results demonstrated that all three kinds of rice bran meal dietary fibers (RBDFs) were irregularly flaky. Fourier transform infrared spectroscopy (FT-IR) results revealed that the three RBDFs had similar reactive groups, and X-ray diffraction (XRD) results indicated that all three RBDFs were cellulose type I crystals. The results of thermogravimetric analysis showed that the lignin content of N-RBDF was significantly lower than that of the other two. Among the three kinds of RBDFs, E-RBDF had higher water retention capacity, swelling capacity, oil holding capacity, and adsorption capacity for cholesterol and sodium bile salts. The results of experimental studies in hyperlipidemic rats showed that all three kinds of RBDFs significantly reduced triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) and elevated high-density lipoprotein cholesterol (HDL-C) in the serum of hyperlipidemic rats; they also significantly lowered malondialdehyde (MDA) and elevated total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) activities in the livers of rats. In addition, all three kinds of RBDFs decreased aminotransferase (ALT) and aminotransferase (AST) activity in serum and also improved liver steatosis and reduced atherosclerosis index (AI) in rats with hyperlipidemia. Our study provides a reference for the development and utilization of rice bran meal and the application of rice bran meal dietary fiber in food processing.

Mystery of bisphenol F-induced nonalcoholic fatty liver disease-like changes: Roles of Drp1-mediated abnormal mitochondrial fission in lipid droplet deposition.

As one of the major substitutes for bisphenol A (BPA), bisphenol F (BPF) has been widely used. Our previous study demonstrated that BPF exposure facilitates lipid droplet deposition in hepatic cells, contributing to nonalcoholic fatty liver disease (NAFLD)-like changes. However, the underlying mechanisms remain poorly understood. Here, with a metabolic cage system, we observed the perturbation of energy metabolism in mice treated with BPF. BPF obviously suppressed metabolic capacity, which manifested as decreased energy expenditure, low O2 consumption and CO2 levels in mice. Consistent with the in vivo results, a Seahorse XF Cell Mito Stress Test showed significant reductions in mitochondrial ATP production capacity, maximum respiratory capacity, and residual respiratory capacity after BPF treatment in an in vitro study. Electron microscopy revealed a striking increase in mitochondrial fission that was synchronous with excessive expression and activation of dynamin-related protein 1 (Drp1). Intriguingly, chemical inhibition of Drp1 by Mdivi-1 and/or silencing of Drp1 dramatically hampered mitochondrial fission and ameliorated BPF-induced lipid droplet deposition both in mouse liver and human hepatic cells. Mechanistically, mitochondrial dynamics imbalance played prominent roles in these processes, since suppression of Drp1 by chemical inhibition or knockdown substantially reversed BPF-induced mitochondrial fission and ameliorated the suppression of mitochondrial metabolism as well as excessive mitochondrial ROS, which was verified to be key to lipid droplet deposition. Collectively, the findings of the current study reveal previously unrecognized effects involving Drp1-mediated mitochondrial injury in BPF-induced lipid droplet deposition. Therefore, targeted intervention against mitochondrial dysfunction may be a promising therapeutic strategy for BPF-induced NAFLD-like changes.

Physicochemical properties of superfine grinding-microwave modified artichoke soluble dietary fiber and their alleviation of alcoholic fatty liver in mice.

The effects of superfine grinding (SG) and microwave treatment (MT) on the structure and physicochemical properties of artichoke soluble dietary fiber (ASDF) and its protective effects on mice with alcoholic fatty liver (AFL) were studied. We compared the changes in structural characteristics and physicochemical properties of ASDF, SG-ASDF (ASDF treated by SG), MT-ASDF (ASDF treated by MT), and CM-ASDF (ASDF treated by SG and MT). Moreover, we evaluated the effects of the obtained ASDF on the growth characteristics, blood lipid levels, and liver of mice with AFL. Our results of the study showed that CM-ASDF had a more concentrated and uniform particle size, a higher extraction rate of ASDF and significantly improved water-holding capacity (WHC), oil-holding capacity (OHC) and water swelling capacity (WSC) of ASDF (p < 0.05). After the ASDF intervention, mice with AFL exhibited a significant improvement in body lipid levels and reduce liver inflammation. Specifically, aspartate aminotransferase (AST), alanine aminotransferase (ALT), malonaldehyde (MDA), Tumor necrosis factor-α (TNF-α) and Interleukin-6 (IL-6) were significantly decreased, while superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) were significantly increased (p < 0.05). And the hematoxylin-eosin (HE) staining results showed significant improvement of hepatic steatosis in mice with AFL. In summary, our study found that both SG and MT could improve the structure and physicochemical properties of ASDF, with CM-ASDF being the most effective. Additionally, CM-ASDF was selected to continue the investigation and demonstrated an excellent protective effect on mice with AFL, with the high dose group (H-ASDF) showing the greatest benefit. These findings provided some new insights for future comprehensive utilization of ASDF and drug development for the treatment of AFL.

Microbiome and tryptophan metabolomics analysis in adolescent depression: roles of the gut microbiota in the regulation of tryptophan-derived neurotransmitters and behaviors in human and mice.

BACKGROUND: Adolescent depression is becoming one of the major public health concerns, because of its increased prevalence and risk of significant functional impairment and suicidality. Clinical depression commonly emerges in adolescence; therefore, the prevention and intervention of depression at this stage is crucial. Recent evidence supports the importance of the gut microbiota (GM) in the modulation of multiple functions associated with depression through the gut-brain axis (GBA). However, the underlying mechanisms remain poorly understood. Therefore, in the current study, we aimed to screen the microbiota out from healthy and depressive adolescents, delineate the association of the targeted microbiota and the adolescent depression, address the salutary effects of the targeted microbiota on anti-depressive behaviors in mice involving the metabolism of the tryptophan (Trp)-derived neurotransmitters along the GBA. RESULTS: Here, we found the gut microbiota from healthy adolescent volunteers, first diagnosis patients of adolescent depression, and sertraline interveners after first diagnosis displayed significant difference, the relative abundance of Faecalibacterium, Roseburia, Collinsella, Blautia, Phascolarctobacterium, Lachnospiraceae-unclassified decreased in adolescent depressive patients, while restored after sertraline treatment. Of note, the Roseburia abundance exhibited a high efficiency in predicting adolescent depression. Intriguingly, transplantation of the fecal microbiota from healthy adolescent volunteers to the chronic restraint stress (CRS)-induced adolescent depressed mice significantly ameliorated mouse depressive behaviors, in which the Roseburia exerted critical roles, since its effective colonization in the mouse colon resulted in remarkably increased 5-HT level and reciprocally decreased kynurenine (Kyn) toxic metabolites quinolinic acid (Quin) and 3-hydroxykynurenine (3-HK) levels in both the mouse brain and colon. The specific roles of the Roseburia were further validated by the target bacteria transplantation mouse model, Roseburia intestinalis (Ri.) was gavaged to mice and importantly, it dramatically ameliorated CRS-induced mouse depressive behaviors, increased 5-HT levels in the brain and colon via promoting tryptophan hydroxylase-2 (TPH2) or -1 (TPH1) expression. Reciprocally, Ri. markedly restrained the limit-step enzyme responsible for kynurenine (indoleamine2,3-dioxygenase 1, IDO1) and quinolinic acid (3-hydroxyanthranilic acid 3,4-dioxygenase, 3HAO) generation, thereby decreased Kyn and Quin levels. Additionally, Ri. administration exerted a pivotal role in the protection of CRS-induced synaptic loss, microglial activation, and astrocyte maintenance. CONCLUSIONS: This study is the first to delineate the beneficial effects of Ri. on adolescent depression by balancing Trp-derived neurotransmitter metabolism and improving synaptogenesis and glial maintenance, which may yield novel insights into the microbial markers and therapeutic strategies of GBA in adolescent depression. Video Abstract.

Protection of Oxygen Glucose Deprivation-Induced Human Brain Vascular Pericyte Injury: Beneficial Effects of Bellidifolin in Cellular Pyroptosis.

Pericytes play critical roles in the maintenance of brain vascular homeostasis. However, very little is currently known about how pericytes regulate ischemic stroke-induced brain injury. Inflammation is a key event in the pathobiology of stroke, in which the nod-like receptor protein-3 (NLRP3) inflammasome is involved in, triggering sterile inflammatory responses and pyroptosis. In the current study, an immortalized cell line derived from human brain vascular pericytes (HBVPs) was constructed, and it showed that HBVPs challenged with oxygen glucose deprivation (OGD) displays pronounced cellular excretion of LDH, IL-1ß, IL-18 and increased PI positive staining. Mechanistically, upon OGD treatment, NLRP3 forms an inflammasome with its adaptor protein apoptosis-associated speck-like protein, containing a caspase recruitment domain (ASC) and caspase-1, manifested as much more co-stainings of NLRP3, ASC and Caspase-1 in HBVPs, accompanied by the increased protein levels of NLRP3, ASC, caspase-1 as well as the pyroptosis-associated protein gasdermin D (GSDMD). Intriguingly, GSDMD-N shuttled to the mitochondrial membrane triggered by OGD exposure, which promoted massive mitochondria-derived ROS generation. Importantly, the invention value of the specific targets was evaluated by treatment with bellidifolin, a kind of ketone compound derived from Swertia chirayita in traditional Tibetan medicine. It showed that bellidifolin exerts beneficial effects and attenuates the formation of NLRP3/ASC/Caspase-1 complex, thereby impeding GSDMD-N shuttling and resultant ROS generation, protecting against OGD-induced HBVPs pyroptosis. Overall, these findings unravel the potential mechanisms of pericyte injury induced by OGD and indicate that bellidifolin may exert its beneficial effects on pyroptosis, thus providing new therapeutic insights into stroke.

Temperature Performance Study of SAW Sensors Based on AlN and AlScN.

In this paper, the temperature performance of AlN-SAW resonators and AlScN-SAW resonators is studied. They are simulated by COMSOL Multiphysics, and their modes and the S11 curve are analyzed. The two devices were fabricated using MEMS technology and tested using VNA, and the test results were consistent with the simulation results. Temperature experiments were carried out with temperature control equipment. With the change in temperature, the changes in S11 parameters, TCF coefficient, phase velocity, and quality factor Q were analyzed. The results show that the temperature performance of the AlN-SAW resonator and the AlScN-SAW resonator is very good, and both have good linearity. At the same time, the sensitivity of the AlScN-SAW resonator is greater by 9.5%, the linearity is greater by 15%, and the TCF coefficient is greater by 11.1%. The temperature performance is excellent, and it is more suitable as a temperature sensor.

A High-Sensitivity MEMS Accelerometer Using a Sc0.8Al0.2N-Based Four Beam Structure.

In this paper, a high-sensitivity microelectromechanical system (MEMS) piezoelectric accelerometer based on a Scandium-doped Aluminum Nitride (ScAlN) thin film is proposed. The primary structure of this accelerometer is a silicon proof mass fixed by four piezoelectric cantilever beams. In order to enhance the sensitivity of the accelerometer, the Sc0.2Al0.8N piezoelectric film is used in the device. The transverse piezoelectric coefficient d31 of the Sc0.2Al0.8N piezoelectric film is measured by the cantilever beam method and found to be -4.7661 pC/N, which is approximately two to three times greater than that of a pure AlN film. To further enhance the sensitivity of the accelerometer, the top electrodes are divided into inner and outer electrodes; then, the four piezoelectric cantilever beams can achieve a series connection by these inner and outer electrodes. Subsequently, theoretical and finite element models are established to analyze the effectiveness of the above structure. After fabricating the device, the measurement results demonstrate that the resonant frequency of the device is 7.24 kHz and the operating frequency is 56 Hz to 2360 Hz. At a frequency of 480 Hz, the sensitivity, minimum detectable acceleration, and resolution of the device are 2.448 mV/g, 1 mg, and 1 mg, respectively. The linearity of the accelerometer is good for accelerations less than 2 g. The proposed piezoelectric MEMS accelerometer has demonstrated high sensitivity and linearity, making it suitable for accurately detecting low-frequency vibrations.

Comparison of single-postlabeling delay and seven-delay three-dimensional pseudo-continuous arterial spin labeling in the assessment of intracranial atherosclerotic disease.

Background: The assessment of cerebral blood flow (CBF) is crucial in the evaluation of intracranial atherosclerotic disease. This study was performed to compare single postlabeling delay (PLD) 3-dimensional pseudo-continuous arterial spin labeling (3D-pCASL) and 7-delay 3D-pCASL magnetic resonance imaging in patients with intracranial atherosclerotic stenosis. Methods: A total of 26 patients with moderate to severe atherosclerotic stenosis or occlusion of an intracranial artery were prospectively enrolled in the study. Perfusion parameters were obtained in various regions of interest (ROIs), namely CBF for single PLDs of 1,525 ms (CBF1525 ms), 2,025 ms (CBF2025 ms), and 2,525 ms (CBF2525 ms) with 3D-pCASL, as well as arterial transit time (ATT) and transit-corrected CBF (CBFtransit-corrected) for 7-delay 3D-pCASL. The consistency of the perfusion parameters between single-PLD 3D-pCASL and 7-delay 3D-pCASL was investigated, and the relationship between vascular stenosis and perfusion parameters was explored. Results: Bland-Altman plots compared the CBF values derived from single-PLD 3D-pCASL to those from CBFtransit-corrected. ATT significantly correlated with the difference between CBFtransit-corrected and CBF1525 ms, CBF2025 ms, and CBF2525 ms, respectively (P<0.05). Binary logistic regression analysis revealed that the CBFtransit-corrected and ATT correlated with the presence of moderate or more severe stenotic vascular territories (P<0.05). Conclusions: The single-PLD 3D-pCASL and the 7-delay 3D-pCASL showed inconsistencies in the assessment of CBF, and the perfusion parameters generated under the standard single-PLD 3D-pCASL were more affected by ATT. Moreover, CBFtransit-corrected and ATT were consistent with stenotic vascular territories, which is useful in the evaluation of intracranial atherosclerotic disease.

A Sensitive and Specific Monoclonal Antibody Based Enzyme-Linked Immunosorbent Assay for the Rapid Detection of Pretilachlor in Grains and the Environment.

Pretilachlor is a chloroacetamide herbicide mainly used for weed and broadleaf weed control in rice, that is widely utilized in China. In order to detect the residue of pretilachlor in the environment and food, a highly sensitive and specific monoclonal antibody (mAb) against pretilachlor was prepared, and the half maximum inhibitory concentration (IC50) of the monoclonal antibody was validated to be 31.47 ± 2.35 µg/L. An indirect competitive ELISA (ic-ELISA) based on the antibody with a linear range of 6.25~100 µg/L was developed. The specificity of the antibody was explained by computer simulations and experimental validation. The mAb exhibited negligible cross-reactivity towards alachlor, acetochlor, propisochlor, butachlor, and metalaxyl, and the limits of detection (LOD) for pretilachlor in lake, rice, and soil samples were 4.83~5.23 µg/L. The recoveries of all samples were 78.3~91.3%. The reliability of the ic-ELISA method for residue detection of pretilachlor in the environment and grains was confirmed using high performance liquid chromatography.

Highly Sensitive Magnetic-Nanoparticle-Based Immunochromatography Assay for Rapid Detection of Amantadine in Chicken and Eggs.

Amantadine (AMD) is an antiviral drug that is prohibited for use in livestock and poultry. In this study, carboxyl-modified magnetic nanoparticles (MNPs) were synthesized using the solvothermal method in one step with harmless and inexpensive regents, and they were used to label monoclonal antibodies (mAbs) of AMD in microwells with electrostatic adsorption. Then, a magnetic immunochromatography assay (MICA) method was successfully established. Under optimal conditions, the MICA showed a good performance, with a linear range of 0.2~10.0 µg/L. The limit of detection (LOD) was 0.068 µg/L with the instrument, and the visual LOD (vLOD) was 0.5 µg/L. There was no cross-reaction with rimantadine and ribavirin. The vLOD in real samples was 1.0 µg/kg. The developed MICA has the advantages of convenience, speed, and sensitivity, which make it suitable for the on-site rapid detection of AMD residues in chicken tissues and eggs.

Altered cerebral blood flow in patients with spinocerebellar degeneration.

Objectives: Spinocerebellar degeneration (SCD) comprises a multitude of disorders with sporadic and hereditary forms, including spinocerebellar ataxia (SCA). Except for progressive cerebellar ataxia and structural atrophy, hemodynamic changes have also been observed in SCD. This study aimed to explore the whole-brain patterns of altered cerebral blood flow (CBF) and its correlations with disease severity and psychological abnormalities in SCD via arterial spin labeling (ASL). Methods: Thirty SCD patients and 30 age- and sex-matched healthy controls (HC) were prospectively recruited and underwent ASL examination on a 3.0T MR scanner. The Scale for Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARS) scores were used to evaluate the disease severity in SCD patients. Additionally, the status of anxiety, depression and sleep among all patients were, respectively, evaluated by the Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS) and Self-Rating Scale of Sleep (SRSS). We compared the whole-brain CBF value between SCD group and HC group at the voxel level. Then, the correlation analyses between CBF and disease severity, and psychological abnormalities were performed on SCD group. Results: Compared with HC, SCD patients demonstrated decreased CBF value in two clusters (FWE corrected P < 0.05), covering bilateral dentate and fastigial nuclei, bilateral cerebellar lobules I-IV, V and IX, left lobule VI, right lobule VIIIb, lobules IX and X of the vermis in the cerebellar Cluster 1 and the dorsal part of raphe nucleus in the midbrain Cluster 2. The CBF of cerebellar Cluster 1 was negatively correlated with SARA scores (Spearman's rho = -0.374, P = 0.042) and SDS standard scores (Spearman's rho = -0.388, P = 0.034), respectively. And, the CBF of midbrain Cluster 2 also had negative correlations with SARA scores (Spearman's rho = -0.370, P = 0.044) and ICARS scores (Pearson r = -0.464, P = 0.010). Conclusion: The SCD-related whole-brain CBF changes mainly involved in the cerebellum and the midbrain of brainstem, which are partially overlapped with the related function cerebellar areas of hand, foot and tongue movement. Decreased CBF was related to disease severity and depression status in SCD. Therefore, CBF may be a promising neuroimaging biomarker to reflect the severity of SCD and suggest mental changes.

Clinical and genetic study of ataxia with vitamin E deficiency: A case report.

BACKGROUND: Ataxia with vitamin E deficiency (AVED) is a type of autosomal recessive cerebellar ataxia. Clinical manifestations include progressive cerebellar ataxia and movement disorders. TTPA gene mutations cause the disease. CASE SUMMARY: We report the case of a 32-year-old woman who presented with progressive cerebellar ataxia, dysarthria, dystonic tremors and a remarkably decreased serum vitamin E concentration. Brain magnetic resonance images showed that her brainstem and cerebellum were within normal limits. Acquired causes of ataxia were excluded. Whole exome sequencing subsequently identified a novel homozygous variant (c.473T>C, p.F158S) of the TPPA gene. Bioinformatic analysis predicted that F185S is harmful to protein function. After supplementing the patient with vitamin E 400 mg three times per day for 2 years, her symptoms remained stable. CONCLUSION: We identified an AVED patient caused by novel mutation in TTPA gene. Our findings widen the known TTPA gene mutation spectrum.

Modification of Artichoke Dietary Fiber by Superfine Grinding and High-Pressure Homogenization and Its Protection against Cadmium Poisoning in Rats.

This study was carried out to investigate the effects of superfine grinding (SP) and high-pressure homogenization (HPH) on the structural and physicochemical properties of artichoke dietary fiber (ADF), as well as the protective effects against cadmium poisoning in rats. The structural characteristics and physicochemical properties of ADF, HPH-ADF (ADF treated by HPH) and CM-ADF (ADF treated by SP and HPH) were determined, and cadmium chloride (CdCl2) was induced by exposing rats for 7 weeks. The amounts of creatinine and urea; the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum; the quantity of red blood cells, hemoglobin, white blood cells and neutrophil proportion in blood samples; and the activity of glutathione peroxidase (GSH-Px) in liver tissue were analyzed. Hematoxylin-eosin (HE) staining was performed to analyze the tissue structure and pathology of the liver and testis. The results showed that ADF subjected to HPH and SP-HPH exhibited increased content of soluble dietary fiber (SDF) (p < 0.05). HPH and SP-HPH treatments increased oil-holding capacity (OHC), total negative charge (TNC) and heavy metal adsorption capacity (p < 0.05). The CdCl2 intervention led to a significant increase in AST, ALT, creatinine, urea, neutrophil proportion and white blood cell count, as well as a significant decrease in GSH-Px activity, red blood cell count and hemoglobin (HGB) (p < 0.05). In rats fed with ADF, HPH-ADF and CM-ADF significantly reduced creatinine, urea amounts, ALT, AST activity in serum, leukocyte count and the neutrophil ratio in blood and increased GSH-Px activity in the liver, in addition to increasing the erythrocyte count and hemoglobin count in blood (p < 0.05). H&E staining results showed that steatosis in the liver was significantly reduced, whereas testicular tissue edema was improved. These results indicate that ADF exhibited positive activity against cadmium poisoning in rats and that CM-ADF had a better protective effect than ADF and HPH-ADF. ADF has specific potential to be used in health foods or therapeutic drugs, providing a reference for the development and utilization of artichoke waste.