The effects of methylphenidate and atomoxetine on Drosophila brain at single-cell resolution and potential drug repurposing for ADHD treatment.

The stimulant methylphenidate (MPH) and the non-stimulant atomoxetine (ATX) are frequently used for the treatment of attention-deficit/hyperactivity disorder (ADHD); however, the function of these drugs in different types of brain cells and their effects on related genes remain largely unknown. To address these questions, we built a pipeline for the simultaneous examination of the activity behavior and transcriptional responses of Drosophila melanogaster at single-cell resolution following drug treatment. We selected the Drosophila with significantly increased locomotor activities (hyperactivity-like behavior) following the administration of each drug in comparison with the control (same food as the drug-treated groups with 5% sucrose, yeast, and blue food dye solution) using EasyFlyTracker. Subsequently, single cell RNA sequencing (scRNASEQ) was used to capture the transcriptome of 82,917 cells, unsupervised clustering analysis of which yielded 28 primary cell clusters representing the major cell types in adult Drosophila brain. Indeed, both neuronal and glial cells responded to MPH and ATX. Further analysis of differentially expressed genes (DEGs) revealed distinct transcriptional changes associated with these two drugs, such as two well-studied dopamine receptor genes (Dop2R and DopEcR) were responsive to MPH but not to ATX at their optimal doses, in addition to genes involved in dopamine metabolism pathways such as Syt1, Sytalpha, Syt7, and Ih in different cell types. More importantly, MPH also suppressed the expression of genes encoding other neurotransmitter receptors and synaptic signaling molecules in many cell types, especially those for Glu and GABA, while the responsive effects of ATX were much weaker. In addition to monoaminergic neuronal transmitters, other neurotransmitters have also shown a similar pattern with respect to a stronger effect associated with MPH than with ATX. Moreover, we identified four distinct glial cell subtypes responsive to the two drugs and detected a greater number of differentially expressed genes associated with ensheathing and astrocyte-like glia. Furthermore, our study provides a rich resource of candidate target genes, supported by drug set enrichment analysis (P = 2.10E-4; hypergeometric test), for the further exploration of drug repurposing. The whole list of candidates can be found at ADHDrug ( http://adhdrug.cibr.ac.cn/ ). In conclusion, we propose a fast and cost-efficient pipeline to explore the underlying molecular mechanisms of ADHD drug treatment in Drosophila brain at single-cell resolution, which may further facilitate drug repurposing applications.

Result of a Pilot External Quality Assessment Scheme for Clinical Diagnosis of Inherited Metabolic Disorders in China.

BACKGROUND: We aimed to evaluate the diagnostic capabilities of Chinese laboratories for inherited metabolic disorders (IMDs) using gas chromatography-mass spectrometry (GC-MS) on urine samples. Meanwhile, based on the result of the pilot external quality assessment (EQA) scheme, we hope to establish a standardized and reliable procedure for future EQA practice. METHODS: We recruited laboratories that participated in the EQA of quantitative analysis of urinary organic acids with GC-MS before joining the surveys. In each survey, a set of five real urine samples was distributed to each participant. The participants should analyze the sample by GC-MS and report the "analytical result", "the most likely diagnosis", and "recommendation for further tests" to the NCCL before the deadline. RESULTS: A total of 21 laboratories participated in the scheme. The pass rates were 94.4% in 2020 and 89.5% in 2021. For all eight IMDs tested, the analytical proficiency rates ranged from 84.7% - 100%, and the interpretational performance rate ranged from 88.2% - 97.0%. The performance on hyperphenylalaninemia (HPA), 3-methylcrotonyl-CoA carboxylase deficiency (MCCD), and ethylmalonic encephalopathy (EE) samples were not satisfactory. CONCLUSIONS: In general, the participants of this pilot EQA scheme are equipped with the basic capability for qualitative organic acid analysis and interpretation of the results. Limited by the small size of laboratories and samples involved, this activity could not fully reflect the state of clinical practice of Chinese laboratories. NCCL will improve the EQA scheme and implement more EQA activities in the future.

[Clinical analysis and genetic diagnosis of three children with Isoleucine metabolic disorders due to variants of HSD17B10 and ACAT1 genes].

OBJECTIVE: To explore the clinical, biochemical and genetic characteristics of three children with Isoleucine metabolic disorders due to variants of HSD17B10 and ACAT1 genes. METHODS: Two children with 17ß hydroxysteroid dehydrogenase 10 (HSD17B10) deficiency and a child with ß-ketothiolase deficiency (BKD) diagnosed at Shanghai Children's Hospital between 2014 and 2021 were selected as the study subjects. Clinical data of the children were collected. The children were subjected to blood acylcarnitine, urinary organic acid and genetic testing, and candidate variants were analyzed with bioinformatic tools. RESULTS: The main symptoms of the three children had included epilepsy, developmental delay, hypotonia and acidosis. Their blood acylcarnitine methylcrotonyl carnitine (C5:1), 3-hydroxyisovalerylcarnitine (C5-OH) and 3-hydroxybutylcarnitine (C4OH) were increased to various extents, and urine organic acids including methyl crotonylglycine and 2-methyl-3-hydroxybutyric acid were significantly increased. Child 1 and child 2 were respectively found to harbor a c.347G>A (p.R116Q) variant and a c.274G>A (p.A92T) variant of the HSD17B10 gene, and child 3 was found to harbor compound heterozygous variants of the ACAT1 gene, namely c.547G>A (p.G183R) and a c.331G>C (p.A111P). Among these, the c.274G>A (p.A92T) and c.331G>C (p.A111P) variants were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), they were respectively classified as variant of unknown significance (PP3_Strong+PM2_supporting) and likely pathogenic (PM3+PM2_Supporting+PP3_Moderate+PP4). CONCLUSION: Both the HSD17B10 deficiency and BKD can lead to Isoleucine metabolism disorders, which may be difficult to distinguish clinically. Genetic testing can further confirm the diagnosis. Discoveries of the HSD17B10: c.274G>A (p.A92T) variant and the ACAT1: c.331G>C (p.A111P) variant have enriched the mutational spectrum of the two diseases.

Novel rare mutation in a conserved site of PTPRB causes human hypoplastic left heart syndrome.

Hypoplastic left heart syndrome (HLHS) is a rare but fatal birth defect in which the left side of the heart is underdeveloped. HLHS accounts for 2% to 4% of congenital heart anomalies. Whole genome sequencing (WGS) was conducted for a family trio consisting of a proband and his parents. A homozygous rare variant was detected in the PTPRB (Protein Tyrosine Phosphatase Receptor Type B) gene of the proband by functional annotation and co-segregation analysis. Sanger sequencing was used to confirm genotypes of the variant. The in silico prediction tools, including Mutation Taster, SpliceAI, and CADD, were used to predict the impact of the mutation. The allele frequencies across populations were compared based on multiple databases, including "1000 genomes" and "gnomAD". We used two vectors (pcMINI and pcDNA3.1) to generate a minigene construct to validate the mutational effect at the transcriptional level. Family-based WGS analyses showed that only a homozygous splice acceptor variant (NC_000012.12: g.70636068T>G, NM_001109754.4: c.56-2A>C, NG_029940.2: g.6373A>C) at the exon-intron border of PTPRB gene associates with HLHS. This variant is also within the region with the enhancer activity based on UCSC genome annotation. Genotyping and Sanger sequencing revealed that the proband's parents are heterozygous for this variant. Evolutionary conservation analysis revealed that the site (NC_000012.12: g.70636068) is extremely conserved across species, supporting the evolutionary functional constraints of the ancestral wild type (T). In silico tools universally predicted a deleterious or disease-causing impact of the mutation from T to G. The mutation was not found in the 1000 genomes and gnomAD databases, which indicates that this mutation is very rare in most human populations. A splicing assay indicated that the mutated minigene caused aberrant splicing of mRNA, in which a 3 bp missing in the second exon resulted in the deletion of one amino acid (NP_001103224.1:p.Glu19del) compared to the normal protein of PRPTB (also the VE-PTP). Structure prediction revealed that the deletion occurred within the C-region of the signal peptide of VE-PTP, suggesting signal peptide-related defects as a potential mechanism for the HLHS cellular pathogeny. We report a rare homozygous variant with splicing error in PTPRB associated with HLHS. Previous model species studies revealed conserved functions of PTPRB in cardiovascular and heart development in mice and zebrafish. Our study is the first report to show the association between PTPRB and HLHS in humans.

Comparison of VTE risk scores in guidelines for VTE diagnosis in nonsurgical hospitalized patients with suspected VTE.

BACKGROUND: The assessment of VTE likelihood with VTE risk scores is essential prior to imaging examinations during VTE diagnostic procedure. Little is known with respect to the disparity of predictive power for VTE diagnosis among VTE risk scores in guidelines for nonsurgical hospitalized patients with clinically suspected VTE. METHODS: A retrospective study was performed to compare the predictive power for VTE diagnosis among the Wells, Geneva, YEARS, PERC, Padua, and IMPROVE scores in the leading authoritative guidelines in nonsurgical hospitalized patients with suspected VTE. RESULTS: Among 3168 nonsurgical hospitalized patients with suspected VTE, VTE was finally excluded in 2733(86.3%) ones, whereas confirmed in 435(13.7%) ones. The sensitivity and specificity resulted from the Wells, Geneva, YEARS, PERC, Padua, and IMPROVE scores were (90.3%, 49.8%), (88.7%, 53.6%), (73.8%, 50.2%), (97.7%,16.9%), (80.9%, 44.0%), and (78.2%, 47.0%), respectively. The YI were 0.401, 0.423, 0.240, 0.146, 0.249, and 0.252 for the Wells, Geneva, YEARS, PERC, Padua, and IMPROVE scores, respectively. The C-index were 0.694(0.626-0.762), 0.697(0.623-0.772), 0.602(0.535-0.669), 0.569(0.486-0.652), 0.607(0.533-0.681), and 0.609(0.538-0.680) for the Wells, Geneva, YEARS, PERC, Padua, and IMPROVE scores, respectively. Consistency was significant in the pairwise comparison of Wells vs Geneva(Kappa 0.753, P = 0.565), YEARS vs Padua(Kappa 0.816, P = 0.565), YEARS vs IMPROVE(Kappa 0.771, P = 0.645), and Padua vs IMPROVE(Kappa 0.789, P = 0.812), whereas it did not present in the other pairs. The YI was improved to 0.304, 0.272, and 0.264 for the PERC(AUC 0.631[0.547-0.714], P = 0.006), Padua(AUC 0.613[0.527-0.700], P = 0.017), and IMPROVE(AUC 0.614[0.530-0.698], P = 0.016), with a revised cutoff of 5 or less, 6 or more, and 4 or more denoting the VTE-likely, respectively. CONCLUSIONS: For nonsurgical hospitalized patients with suspected VTE, the Geneva and Wells scores perform best, the PERC scores performs worst despite its significantly high sensitivity, whereas the others perform intermediately, albeit the absolute predictive power of all isolated scores are mediocre. The predictive power of the PERC, Padua, and IMPROVE scores are improved with revised cutoffs.

Danggui Buxue Decoction: Comparative pharmacokinetic research on six bio-active components in different states by ultra-performance liquid chromatography-tandem mass spectrometry after oral administration.

Danggui Buxue Decoction is a classic formula containing Astragali Radix and Angelicae Sinensis Radix in a 5:1 ratio and has been extensively used to treat blood deficiency for thousands of years. The aim of the study was to investigate the differences in plasma protein binding, pharmacokinetics, and tissue distribution of Danggui Buxue Decoction in normal and blood-deficient rats by ultra-performance liquid chromatography-tandem mass spectrometry. The effects on peripheral blood routine were verified. The compounds exhibited higher plasma protein binding and absorption in the model group compared to the control group, except formononetin. The six ingredients were distributed widely, and the highest concentrations were detected in the heart and uterus. As has been demonstrated in the previous study of the effect of Danggui Buxue Decoction, its potential is to serve as an effective traditional Chinese medicine formula for treating cardiovascular diseases and impacting estrogenic properties, which reveals the potential target organs of Danggui Buxue Decoction the heart and uterus. Our findings suggested that the absorption and distribution of different components in Danggui Buxue Decoction varies depending on the pathological state, molecular weight, lipid solubility, transporter-mediated efflux, and other factors.

Study on the dynamic metabolic characteristic of main active ingredients in Danggui Buxue Decoction by liquid chromatography-tandem mass spectrometry based on in situ sequential metabolism strategy.

Danggui Buxue Decoction is a classic formula for replenishing qi and nourishing blood. Despite its widespread use, its dynamic metabolism involved remains unclear. Based on the sequential metabolism strategy, blood samples from different metabolic sites were obtained via in situ closed intestine ring integrated with a jugular venous continuous blood supply technique. An ultra-high-performance liquid chromatography-linear triple quadruple-Orbitrap-tandem mass spectrometry method was developed for the identification of prototypes and metabolites in rat plasma. The dynamic absorption and metabolic landscape of flavonoids, saponins, and phthalides were characterized. Flavonoids could be deglycosylated, deacetylated, demethylated, dehydroxylated, and glucuronicated in the gut and then absorbed for further metabolism. Jejunum is an important metabolic site for saponins biotransformation. Saponins that are substituted by Acetyl groups tend to lose their acetyl groups and convert to Astragaloside IV in the jejunum. Phthalides could be hydroxylated and glucuronidated in the gut and then absorbed for further metabolism. Seven components serve as crucial joints in the metabolic network and are potential candidates for the quality control of Danggui Buxue Decoction. The sequential metabolism strategy described in this study could be useful for characterizing the metabolic pathways of Chinese medicine and natural products in the digestive system.

Spatiotemporal Epidemiology of the Gonorrhea Epidemic in Relation to Neighborhood-level Structural Factors in an Eastern Province of China, 2016-2020.

Context: Gonorrhea, a highly communicable, sexually transmitted infection, remains a major public-health concern globally. In recent years, Zhejiang province, an eastern province, has had the highest incidence of gonorrhea in China. Objective: The study intended to identify the geographic distribution patterns and spaciotemporal clustering characteristics of the disease's incidence in Zhejiang between 2016 and 2020, to understand the spatial epidemiology of gonorrhea and to pinpoint the locations with relatively high risks of gonorrhea, the hotspots, which could be the key areas for disease prevention and control. Design: The research team performed a retrospective, spaciotemporal-clustering analysis of data about newly reported gonorrhea cases from January 2016 to December 2020 in Zhejiang province, using the China Information System for Disease Control and Prevention. Setting: The study took place at the Zhejiang Provincial Institute of Dermatology in Huzhou, China. Outcome Measures: The research team: (1) used the Geographic Information System software-ArcGIS 10.8 software to draw statistical maps; (2) conducted a spatial-pattern clustering analysis at the district or county level; (3) performed an autocorrelation analysis using Getis-Ord (Gi*) statistics to detect spatial patterns and the hotspots of gonorrhea incidence; and (4) used SaTScan9.7 to analyze the space-time clusters. Results: Zhejiang province reported 85 904 gonorrhea cases from 2016 to 2020, with a male to female ratio of 3.81:1. The average annual incidence rate of gonorrhea was 30.50 per 100 000 individuals in the population, ranging from 22.73 cases to 39.65 cases, and the annual incidence showed a significant downward trend over the five years (χ2 = 16.142, P < .001). The northern and central areas had a higher incidence than the southern area did. Autocorrelation analysis showed that the gonorrhea incidence had a significantly clustered distribution (Moran's I from 0.197 to 0.295, Z score from 4.749 to 6.909, P < .001). The high-high cluster areas were mainly in the urban districts of Hangzhou and some counties and districts of Jiaxing. The Gi* statistics further indicated that the hotspots of gonorrhea were mainly in Hangzhou, Jiaxing, and Huzhou. The Kuldorff's scan identified two clusters, mainly composed of 36 counties or districts in northern Zhejiang, such as Hangzhou and Jiaxing, and central Zhejiang, such as Jinhua and Shaoxing. Conclusions: The gonorrhea incidence rates in northern and central Zhejiang from 2016 to 2020 were higher than those in southern Zhejiang. An area of relatively higher risk for gonorrhea existed mainly in the urban districts of Hangzhou and some counties and districts of Jiaxing, Jinhua, and Shaoxing. In the future, the research team plans to focus on strengthening the prevention and control measures against gonorrhea in those areas.

Exosomes; a Potential Source of Biomarkers, Therapy, and Cure for Type-1 Diabetes.

The scourge of type-1 diabetes (T1D) is the morbidity and mortality it and its complications cause at a younger age. This propels the constant search for better diagnostic, treatment, and management strategies, with the ultimate quest being a cure for T1D. Recently, the therapeutic potential of exosomes has generated a lot of interest. Among the characteristics of exosomes of particular interest are (a) their regenerative capacity, which depends on their "origin", and (b) their "content", which determines the cell communication and crosstalk they influence. Other functional capacities, including paracrine and endocrine homeostatic regulation, pathogenic response ability resulting in insulin secretory defects or ß-cell death under normal metabolic conditions, immunomodulation, and promotion of regeneration, have also garnered significant interest. Exosome "specificity" makes them suitable as biomarkers or predictors, and their "mobility" and "content" lend credence to drug delivery and therapeutic suitability. This review aims to highlight the functional capacities of exosomes and their established as well as novel contributions at various pathways in the onset and progression of T1D. The pathogenesis of T1D involves a complex crosstalk between insulin-secreting pancreatic ß-cells and immune cells, which is partially mediated by exosomes. We also examine the potential implications for type 2 diabetes (T2D), as the link in T2D has guided T1D exploration. The collective landscape presented is expected to help identify how a deeper understanding of exosomes (and their cargo) can provide a framework for actionable solutions to prevent, halt, or change the very course of T1D and its complications.

Three-dimensional quantitative analysis of dental and skeletal characteristics of skeletal Class I unilateral posterior crossbite in adults.

BACKGROUND: To study the dentoskeletal characteristics and the degree of compensations in skeletal Class I adults with unilateral posterior crossbite (UPCB). METHODS: A sample of 40 adults was chosen for this cross-sectional study. 20 skeletal Class I adults with UPCB (mean age: 22.20 ± 2.88 years), were compared to 20 skeletal Class I adults with normal occlusion (mean age: 27.56 ± 5.76 years). The respective dentoskeletal measurements were made on cross-sectional images from cone-beam computed tomography scans. RESULTS: Skeletally, both groups showed significant differences (P < 0.05) in mandibular corpus length and menton deviation with the UPCB group showing the greatest displacement. Maxillomandibular vertical asymmetry and condylar positional asymmetry were not significant in both groups (P > 0.05). For dental variables on the second premolar and first molar, the UPCB group showed greater linear and angular differences when compared to the control group (P < 0.05). On the crossbite side, maxillary posterior teeth were more buccally inclined, and mandibular posterior teeth were more lingually inclined. However, on the non-crossbite side, both maxillary and mandibular posterior teeth were lingually inclined. CONCLUSION: Adults with UPCB showed distinct transverse dentoskeletal asymmetry. No asymmetry was found in the condylar position and the mandibular height in UPCB adults.

Optimal authoritative risk assessment score of Cancer-associated venous thromboembolism for hospitalized medical patients with lung Cancer.

BACKGROUND: Cancer-associated venous thromboembolism (VTE) is common in patients with primary lung cancer. It has been understudied which authoritative risk assessment score of cancer-associated VTE is optimal for the assessment of VTE development in hospitalized medical patients with lung cancer. METHODS: Patients with lung cancer who had undergone computed tomography pulmonary angiography (CTPA), compression ultrasonography (CUS) of lower and upper extremities, and/or planar ventilation/perfusion (V/Q) scan to confirm the presence or absence of VTE during a medical hospitalization were retrospectively reviewed. Based on the actual prevalence of VTE among all patients, the possibility of VTE were reassessed with the Khorana score, the PROTECHT score, the CONKO score, the ONKOTEV score, the COMPASS-CAT score, and the CATS/MICA score, to compare their assessment accuracy for VTE development. RESULTS: A total of 1263 patients with lung cancer were incorporated into the final analysis. With respect to assessment efficiency for VTE occurrence, the scores with adjusted agreement from highest to lowest were the ONKOTEV score (78.6%), the PROTECHT score (73.4%), the CONKO score (72.1%), the COMPASS-CAT score (71.7%), the Khorana score (70.9%), and the CATS/MICA score (60.3%). The ONKOTEV score had the highest Youden index which was 0.68, followed by the PROTECHT score (0.58), the COMPASS-CAT score (0.56), the CONKO score (0.55), the Khorana score (0.53), and the CATS/MICA score (0.23). CONCLUSIONS: Among the Khorana score, the PROTECHT score, the CONKO score, the ONKOTEV score, the COMPASS-CAT score, and the CATS/MICA score which are approved by authoritative guidelines, the ONKOTEV score is optimal for the assessment of VTE development in hospitalized medical patients with lung cancer.

Comparative Effect of Liuzijue Qigong and Conventional Respiratory Training on Trunk Control Ability and Respiratory Muscle Function in Patients at an Early Recovery Stage From Stroke: A Randomized Controlled Trial.

OBJECTIVES: To compare the effects of Liuzijue Qigong and conventional respiratory training on trunk control ability and respiratory muscle functions in patients at an early recovery stage from stroke. DESIGN: A single-blind, randomized controlled trial. SETTING: A hospital. PARTICIPANTS: Patients (N=60) within 2 months poststroke. INTERVENTIONS: The experimental group (n=30) received conventional rehabilitation training combined with Liuzijue exercise, and the control group (n=30) received conventional rehabilitation training combined with conventional respiration training. The training in the 2 groups was conducted 5 times per week for 3 weeks. MAIN OUTCOME MEASURES: Trunk Impairment Scale (TIS), maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF), maximum expiratory mid-flow (MMEF), diaphragmatic movement, the change of intra-abdominal pressure (IAP), Berg Balance Scale (BBS), and Modified Barthel Index (MBI). All outcome measures were assessed twice (at baseline and 3 weeks). RESULTS: Both groups significantly improved in TIS, MIP, FVC, PEF, and the change of IAP, BBS, and MBI when pre- and postassessments (P<.05) were compared. Compared with the control group, there was a significant difference in the experimental group in the static sitting balance subscale (P=.014), dynamic balance subscale (P=.001), coordination subscale (P<.001), TIS total scores (P<.001; effect size [ES]=0.9), MIP (P=.012; 95% confidence interval [CI], 2.23-17.69; ES=0.67), MEP (P=.015; 95% CI, 1.85-16.57; ES=0.65), change of IAP (P=.001), and MBI (P=.016; 95% CI, 1.51-14.16; ES=0.64). No significant differences were found between the 2 groups in FEV1 (P=.24), FVC (P=.43), PEF (P=.202), MMEF (P=.277), the diaphragmatic movement of quiet breathing (P=.146), deep breathing (P=.102), and BBS (P=.124). CONCLUSIONS: Liuzijue exercise showed more changes than conventional respiratory training in improving trunk control ability, respiratory muscle functions, and activities of daily living ability in patients at an early recovery stage from stroke.

Very long chain acylcarnitines and lysophosphatidylcholines in screening of peroxisomal disease in children by tandem mass spectrometry.

To investigate the value of very long chain acylcarnitine (VLCAC) and lysophosphatidylcholine (LPC) in screening of peroxisomal disease in children. Eighteen children with peroxisomal disease, including 14 cases of X-linked adrenoleukodystrophy (X-ALD group) and 4 cases of Zellweger syndrome (ZS group) diagnosed based on clinical symptoms, MRI and genetic tests were enrolled in the study; and 200 healthy children were selected as control group. Samples of dried blood spots were collected from all subjects, VLCAC and LPC in dried blood spots were extracted by solvent containing internal isotopic standards hexacosanoylcarnitine (H-C26) and C26:0 lysophosphatidylcholine (H-C26:0-LPC). The eicosanoylcarnitine (C20), docosanoylcarnitine (C22), tetracosanoylcarnitine (C24), hexacosanoylcarnitine (C26), C20:0 lysophosphatidylcholine (C20:0-LPC), C22:0 lysophosphatidylcholine (C22:0-LPC), C24:0 lysophosphatidylcholine (C24:0-LPC) and C26:0 lysophosphatidylcholine (C26:0-LPC) were detected by tandem mass spectrometry (MS/MS). The above 8 indicators and the ratios were compared among the groups using Kruskal-Wallis test and Mann-Whitney test; the contribution of each index to the disease were analyzed by partial least square method. Except C24:0-LPC/C20:0-LPC, there were significant differences in all indicators and ratios among all groups (<0.05 or <0.01). There were differences in most indicators and ratios between X-ALD group and the control group, as well as between ZS group and the control group, but there was no difference between the X-ALD group and the ZS group. PLS-DA analysis showed that the peroxisome disease group (including X-ALD group and ZS group) and the control group were able to be completely separated, and C26 had the highest variable importance for the projection (VIP) value. MS/MS detection of VLCAC and LPC can be used as a screening method for peroxisomal disease, and C26 may be a sensitive indicator for diagnosis.

Exploring New Zintl Phases in the 9-4-9 Family via Al Substitution. Synthesis, Structure, and Physical Properties of Ae9Mn4-xAlxSb9 (Ae = Ca, Yb, Eu).

Three new quaternary Zintl phases with the "9-4-9" formula, Ae9Mn4-xAlxSb9 (Ae = Ca, Yb, Eu), have been synthesized using Pb as the metal flux, and their crystal structures have been established by single-crystal X-ray diffraction. Both Ca9Mn2.91(4)Al1.09Sb9 and Yb9Mn3.59(6)Al0.41Sb9 are isostructural with Ca9Mn4Bi9, and they crystallize in the orthorhombic space group Pbam with unit cell dimensions of a = 12.4571(8), 12.2884(16) Å, b = 22.1352(16), 22.024(3) Å, and c = 4.6012(3), 4.6187(6) Å, respectively. Their anionic structures can be viewed as infinite ribbons based on corner-shared tetrahedrons. Also, Eu9Mn2.87(4)Al1.13Sb9 has the space group Cmca and a = 9.4883(7) Å, b = 23.6895(18) Å, and c = 24.4845(19) Å. The structural relationships between Ca9Mn2.91(4)Al1.09Sb9 and Eu9Mn2.87(4)Al1.13Sb9 are compared and discussed as well. The successful Al3+ substitution provides additional electrons to the compounds to achieve structural stability. Magnetic susceptibility and electrical resistivity measurements, performed on single crystals of Eu9Mn2.87(4)Al1.13Sb9, indicate complex magnetic properties and semiconductor behavior. The physical properties of Yb9Mn3.59(6)Al0.41Sb9 are similar to those observed for Yb9Mn4.18(2)Sb9.

Corrosion resistance of itaconic acid doped polyaniline /nanographene oxide composite coating.

Graphene oxide (GO) and polyaniline (PANI) are very unique materials with broad potential in corrosion protection coating. To achieve the maximum stability and anti-corrosion effect in a polar medium, firstly itaconic acid doped PANI (DP) was readily prepared by a one-step method, followed by forming a GO and DP composite (GODP). Characterization by Fourier transform infrared spectroscopy and ultraviolet-visible absorption spectra provides evidence for the successful doping of itaconic acid in PANI. X-ray diffraction analysis shows that the d-spacing of the GO sheets increases slightly with the intercalation of DP. The morphological studies show disordered structures in GODP compared with the original GO sheets due to the introduction of PANI molecules and the interaction of functional groups on the surface of the GO sheets. Thermogravimetric analysis reveals the good thermal stability of DP and GODP. Quantum calculation further confirms the successful doping of itaconic acid, and the effective complex of GO and DP, providing a quantitative understanding of the curing mechanism. The crosslinking interaction among the GODP, curing agent, and epoxy resin facilitates the formation of a compact coating, leading to excellent corrosion resistance toward Mg alloy.

Effects of radial extracorporeal shockwave therapy on spasticity of upper-limb agonist/antagonist muscles in patients affected by stroke: a randomized, single-blind clinical trial.

BACKGROUND: the effects of radial extracorporeal shock wave therapy (rESWT) were assessed on agonist/antagonist muscles in stroke patients with elbow spasticity, the duration of effects and influence on function. METHODS: patients were randomly assigned into groups: control (A, n = 25), rESWT on agonist muscles (B, n = 27) and rESWT on antagonist muscles (C, n = 30) groups. Conventional physical therapy was given to three groups for 3 weeks, six times a week, and besides, rESWT was given at 4-day intervals for five consecutive treatments, B received rESWT on agonist muscles and C received rESWT on antagonist muscles. The primary outcome was Modified Ashworth Scale (MAS) scores. Modified Tardieu Scale, Visual Analogue Scale (VAS), Fugl-Meyer Assessment and swelling scale (SS) scores were secondary outcomes. Indicators were assessed at baseline, after five treatments and after 4 weeks follow-up. RESULTS: the rate of treatment was determined by changes in MAS, which was 16.0 (A), 70.4 (B) and 63.3% (C) after rESWT treatments, and was 24.0 (A), 74.1 (B) and 66.7% (C) after 4 weeks follow-up. Improvements were achieved for R1 (P < 0.01), R2 (P < 0.01) and VAS (P < 0.01) after five rESWT interventions. At 4 weeks, significant improvements were achieved for R1 (P < 0.01) and VAS (P < 0.01). CONCLUSIONS: rESWT is an effective therapy for spasticity after stroke, with lasting effects on both agonist and antagonist muscles after 4 weeks. rESWT relieved pain but had no effect on active function or swelling of the upper limbs.

Self-reduction derived nickel nanoparticles in CdS/Ni(OH)2 heterostructure for enhanced photocatalytic hydrogen evolution.

Nickel-based materials have been used in electrochemical water splitting and as a co-catalyst to effectively improve photocatalytic activity. However, the mechanism of the catalytic effect on hydrogen evolution of NiO and Ni(OH)2 needs further investigation because of the high risk in self-reduction with photo-induced electrons. In this work, the self-reduction of Ni2+ was confirmed during the photocatalytic H2 evolution in the CdS/Ni(OH)2 hybrid materials. Meanwhile, in situ formed metallic Ni plays an important role in the increase in the catalytic activity. Fortunately, only a few photo-induced electrons participate in the reduction of Ni2+ in CdS/Ni(OH)2 hybrid materials. The existence of metallic Ni would prevent more Ni2+ from self-reduction. The synergistic effect of Ni(OH)2 and metallic Ni contributes to the improvement of H2 evolution of CdS nanorods.

Effects of a 3D-printed orthosis compared to a low-temperature thermoplastic plate orthosis on wrist flexor spasticity in chronic hemiparetic stroke patients: a randomized controlled trial.

OBJECTIVE: The aim of this study was to compare the effects of two kinds of wrist-hand orthosis on wrist flexor spasticity in chronic stroke patients. DESIGN: This is a randomized controlled trial. SETTING: The study was conducted in a rehabilitation center. PARTICIPANTS: A total of 40 chronic hemiparetic stroke patients with wrist flexor spasticity were involved in the study. INTERVENTIONS: Patients were randomly assigned to either an experimental group (conventional rehabilitation therapy + 3D-printed orthosis, 20 patients) or a control group (conventional rehabilitation therapy + low-temperature thermoplastic plate orthosis, 20 patients). The time of wearing orthosis was about 4-8 hours per day for six weeks. MAIN MEASURES: Primary outcome measure: Modified Ashworth Scale was assessed three times (at baseline, three weeks, and six weeks). Secondary outcome measures: passive range of motion, Fugl-Meyer Assessment score, visual analogue scale score, and the swelling score were assessed twice (at baseline and six weeks). The subjective feeling score was assessed at six weeks. RESULTS: No significant difference was found between the two groups in the change of Modified Ashworth Scale scores at three weeks (15% versus 25%, P = 0.496). At six weeks, the Modified Ashworth Scale scores (65% versus 30%, P = 0.02), passive range of wrist extension (P < 0.001), ulnar deviation (P = 0.028), Fugl-Meyer Assessment scores (P < 0.001), and swelling scores (P < 0.001) showed significant changes between the experimental group and the control group. No significant difference was found between the two groups in the change of visual analogue scale scores (P = 0.637) and the subjective feeling scores (P = 0.243). CONCLUSION: 3D-printed orthosis showed greater changes than low-temperature thermoplastic plate orthosis in reducing spasticity and swelling, improving motor function of the wrist and passive range of wrist extension for stroke patients.

[Dietary exposure assessment of cadmium of adults in Jiangxi Province in 2016].

OBJECTIVE: To evaluate dietary exposure of cadmium and their potential health risks of adults in Jiangxi Province. METHODS: The concentration data of cadmium of 11 kinds of foods were obtained from food safety monitoring in Jiangxi Province in 2012-2017. The food consumption data was obtained from food consumption survey in Jiangxi Province in 2016. Based on the deterministic assessment model, the dietary exposure of cadmium of adults in Jiangxi Province was calculated. RESULTS: The average dietary exposure of cadmium was 18. 426 µg/kg per month, accounting for 73. 7% of the provisional tolerable monthly intake(PTMI). The large portion exposure(P95) of cadmium was 29. 724 µg/kg per month, accounting for 118. 9% of PTMI. The average and the large portion(P95) dietary exposure range of cadmium in different age groups were 16. 224-19. 774 and 24. 059-33. 387 µg/kg per month, respectively. It was indicated that the main dietary sources of cadmium were rice and vegetables, which were contributed more than 92% of total dietary exposure of cadmium. CONCLUSION: The potential health risks caused by dietary exposure to cadmium of adults in Jiangxi Province was at an acceptable level. But there were some potential health risks in high exposure population.

BplMYB46 from Betula platyphylla Can Form Homodimers and Heterodimers and Is Involved in Salt and Osmotic Stresses.

MYB proteins play important roles in the regulation of plant growth, development, and stress responses. Overexpression of BplMYB46 from Betula platyphylla improved plant salt and osmotic tolerances. In the present study, the interaction of eight avian myeloblastosis viral oncogene homolog (MYB) transcription factors with BplMYB46 was investigated using the yeast two-hybrid system, which showed that BplMYB46 could form homodimers and heterodimers with BplMYB6, BplMYB8, BplMYB11, BplMYB12, and BplMYB13. Relative beta-glucuronidase activity and chromatin immunoprecipitation assays showed that the interaction between BplMYB46 and the five MYBs increased the binding of BplMYB46 to the MYBCORE motif. A subcellular localization study showed that these MYBs were all located in the nucleus. Real-time fluorescence quantitative PCR results indicated that the expressions of BplMYB46 and the five MYB genes could be induced by salt and osmotic stress, and the BplMYB46 and BplMYB13 exhibited the most similar expression patterns. BplMYB46 and BplMYB13 co-overexpression in tobacco using transient transformation technology improved tobacco's tolerance to salt and osmotic stresses compared with overexpressing BplMYB13 or BplMYB46 alone. Taken together, these results demonstrated that BplMYB46 could interact with five other MYBs to form heterodimers that activate the transcription of target genes via an enhanced binding ability to the MYBCORE motif to mediate reactive oxygen species scavenging in response to salt and osmotic stresses.