Domain-specific phenotypes in LINS1-related disorder-A Chinese family with the Q92X variant and literature review.

LINS1 is the human homolog of the Drosophila segment polarity gene that encodes an essential regulator of the wingless/Wnt signaling. By 2011, only seven pedigrees (16 patients) with eight causative variants in LINS1 gene have been reported. These cases mainly presented with infancy-/child-onset neurodevelopmental disorders, facial dysmorphia, and other clinical features, and a wide spectrum of clinically distinct phenotypes were also manifested. In our study, two brothers in a family were admitted and diagnosed with child-onset movement disorders, slight intellectual disability, psychological symptoms, eye problems, urinary and bowel dysfunction, mitral value prolapse, and Q-T prolongation. By exome sequencing, we identified a nonsense homozygous pathogenic variant (LINS1: c.274C > T (p.Q92X)), which had been reported in a case diagnosed with intellectual disability and psychiatric disorders (such as schizophrenia and anxiety). Compared with this case, the clinical features of our cases were distinct. In particular, our cases displayed unusual features of heart and blood system. Furthermore, the genotype-phenotype relationship analysis suggested that distinct phenotypes presented in cases carrying variants in different domains of the LINS1 gene. In conclusions, our findings suggest the high clinical variations in the LINS1 variants-related disorders. Moreover, the Q92X might be a recurrent variant in Hans of Southern China.

Clinical, genetic, and neuroimaging profiles of autosomal recessive spinocerebellar ataxia type 4 caused by novel VPS13D variants in Chinese.

Autosomal recessive spinocerebellar ataxias (SCARs) are a heterogeneous group of neurodegenerative disorders. VPS13D gene is currently the only gene associated with autosomal recessive spinocerebellar ataxia type 4 (SCAR4), also known as VPS13D dyskinesia. SCAR4 is a rare inherited disease, with only 34 reported cases reported worldwide. In this study, we reported three independent SCAR4 cases with adolescent onsets caused by five novel variants of the VPS13D gene. Each patient carried one frameshift and one missense variant: Patient 1 with c.10474del and c.9734C > A (p.Leu3492Tyrfs*43 and p.Thr3245Asn), Patient 2 with c.6094_6107delGTTCTCTTGATCCC and c.9734C > A (p.Val2032Argfs*7 and p.Thr3245Asn), and Patient 3 with c.11954_11963del and c.9833 T > G (p.Phe3985Serfs*10 and p.Ile3278Ser). Two of the three patients shared nystagmus with an identical variant c.9734C > A. Magnetic resonance imaging indicated thoracic spinal atrophy in all three patients and corpus callosum atrophy in one patient, along with other typical manifestations of white matter degradation, cerebral atrophy, and cerebellar atrophy. These findings expanded the genetic, clinical, and neuroimaging spectrum of SCAR4, and provided new insights into the genetic counseling, molecular mechanisms, and differential diagnosis of the disease.

Genetic profiles of multiple system atrophy revealed by exome sequencing, long-read sequencing and spinocerebellar ataxia repeat expansion analysis.

BACKGROUND AND PURPOSE: Multiple system atrophy (MSA) is a progressive, adult-onset neurodegenerative disorder clinically characterized by combinations of autonomic failure, parkinsonism, cerebellar ataxia and pyramidal signs. Although a few genetic factors have been reported to contribute to the disease, its mutational profiles have not been systemically studied. METHODS: To address the genetic profiles of clinically diagnosed MSA patients, exome sequencing and triplet repeat detection was conducted in 205 MSA patients, including one familial case. The pathogenicity of variants was determined according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology guidelines. RESULTS: In the familial patient, a novel heterozygous COQ2 pathogenic variant (p.Ala351Thr) was identified in the MSA pedigree. In the sporadic patients, 29 pathogenic variants were revealed in 21 genes, and the PARK7 p.Ala104Thr variant was significantly associated with MSA (p = 0.0018). Moreover, burden tests demonstrated that the pathogenic variants were enriched in cerebellar ataxia-related genes in patients. Furthermore, repeat expansion analyses revealed that two patients carried the pathogenic CAG repeat expansion in the CACNA1A gene (SCA6), one patient carried the (ACAGG)exp/(ACAGG)exp expansion in RFC1 and one carried the GAA-pure expansion in FGF14 gene. CONCLUSION: In conclusion, a novel COQ2 pathogenic variant was identified in a familial MSA patient, and repeat expansions in CACNA1A, RFC1 and FGF14 gene were detected in four sporadic patients. Moreover, a PARK7 variant and the burden of pathogenic variants in cerebellar ataxia-related genes were associated with MSA.

Novel mutations and molecular pathways identified in patients with brain iron accumulation disorders.

Brain iron accumulation disorders (BIADs) are a group of diseases characterized by iron overload in deep gray matter nuclei, which is a common feature of neurodegenerative diseases. Although genetic factors have been reported to be one of the etiologies, much more details about the genetic background and molecular mechanism of BIADs remain unclear. This study aimed to illustrate the genetic characteristics of BIADs and clarify their molecular mechanisms. A total of 84 patients with BIADs were recruited from April 2018 to October 2022 at Xuanwu Hospital. Clinical characteristics including family history, consanguineous marriage history, and age at onset (AAO) were collected and assessed by two senior neurologists. Neuroimaging data were conducted for all the patients, including cranial magnetic resonance imaging (MRI) and susceptibility-weighted imaging (SWI). Whole-exome sequencing (WES) and capillary electrophoresis for detecting sequence mutation and trinucleotide repeat expansion, respectively, were conducted on all patients and part of their parents (whose samples were available). Variant pathogenicity was assessed according to the American College of Medical Genetics and Association for Molecular Pathology (ACMG/AMP). The NBIA and NBIA-like genes with mutations were included for bioinformatic analysis, using Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genome (KEGG). GO annotation and KEGG pathway analysis were performed on Metascape platform. In the 84 patients, 30 (35.7%) were found to carry mutations, among which 20 carried non-dynamic mutations (missense, stop-gained, frameshift, inframe, and exonic deletion) and 10 carried repeat expansion mutations. Compared with sporadic cases, familial cases had more genetic variants (non-dynamic mutation: P=0.025, dynamic mutation: P=0.003). AAO was 27.85±10.42 years in cases with non-dynamic mutations, which was significantly younger than those without mutations (43.13±17.17, t=3.724, P<0.001) and those with repeated expansions (45.40±8.90, t=4.550, P<0.001). Bioinformatic analysis suggested that genes in lipid metabolism, autophagy, mitochondria regulation, and ferroptosis pathways are more likely to be involved in the pathogenesis of BIADs. This study broadens the genetic spectrum of BIADs and has important implications in genetic counselling and clinical diagnosis. Patients diagnosed as BIADs with early AAO and family history are more likely to carry mutations. Bioinformatic analysis provides new insights into the molecular pathogenesis of BIADs, which may shed lights on the therapeutic strategy for neurodegenerative diseases.

Fermented Cerasus humilis fruits protect against high-fat diet induced hyperlipidemia which is associated with alteration of gut microbiota.

BACKGROUND: Hyperlipidemia is regarded as a public health matter, and its effective prevention and treatment are urgently required. However, the treatment of hyperlipidemia is still relatively scarce. RESULTS: Fermented Cerasus humilis fruit (FCHF) had higher total flavonoid, total phenolic, procyanidin, and organic and free amino acid content, and lower total sugar content, than non-fermented C. humilis fruit (NFCHF). Both FCHF and NFCHF treatment significantly prevent putting on weight. Furthermore, FCHF administration ameliorated hyperlipidemia and cholesterol over-accumulation. In addition, FCHF administration activated the antioxidase system and decreased the malondialdehyde content to relieve oxidative stress, and showed more efficaciously than NFCHF administration. FCHF treatments significantly reverse the fat deposition in high-fat diet rat liver. FCHF supplementation can relieve the dysbacteriosis induced by hyperlipidemia, and regulate the composition of rat gut microbiota by increasing the abundance of Prevotella and norank_f_Muribaculaceae. CONCLUSION: Lactobacillus plantarum and Saccharomyces cerevisiae fermentation enhanced the antihyperlipidemic property of C. humilis fruits by promoting gut microbiota regulation. © 2022 Society of Chemical Industry.

The complete chloroplast genome sequence of Vincetoxicum mongolicum (Apocynaceae), a perennial medicinal herb.

Vincetoxicum mongolicum Maxim. (1876), is a perennial medicinal herb, widely distributed in the Loess Plateau of China. Here, we sequenced, assembled, and annotated the complete chloroplast (cp) genome of V. mongolicum, and compared the highly variable gene regions and phylogenetic positions between V. mongolicum and other related species. Results showed that the complete cp genome of V. mongolicum was 160,157 bp in length, containing a large single copy (LSC) region of 91,263 bp, a pair of inverted repeats (IR) region of 23,892 bp, and a small single copy (SSC) region of 21,110 bp. The GC content accounts for 37.8%, and we annotated 131 single genes, which include 86 protein-coding genes, 8 rRNA genes, and 37 tRNA genes. By comparing and analyzing the variable region of the cp gene of V. mongolicum and other Vincetoxicum, we found that the variable sequences of rpoC1-rpoB, ycf4-cemA, ndhF, ndhF-rpl32, and rpl32-ccsA fragments were highly significant, which could be targeted as the DNA barcodes for evidence of V. mongolicum and its relatives in Apocynaceae. Maximum-likelihood (ML) phylogenetic tree analysis elucidated that V. mongolicum was sister to V. pycnostelma with strong support. Our results provide useful information for future phylogenetic studies and plastid super-barcodes of the family Apocynaceae.

Hartnup disease presenting as hereditary spastic paraplegia and severe peripheral neuropathy.

Hartnup disease cases were rare, and the genotype-phenotype correlation was not fully understood. Here we reported two unrelated young men diagnosed as Hartnup disease, who carried novel compound heterozygote mutations in the SLC6A19 gene and presented with new phenotypes. Other than intermittent encephalopathy and photosensitive rashes, they displayed symptoms and signs of spastic paraplegia and severe peripheral nerve damages. Magnetic resonance imaging showed mild bilateral cerebellar atrophy and thinning of the thoracic spinal cord. Electromyogram detected mixed sensorimotor polyneuropathy in lower limbs. Sural nerve biopsy and pathological study indicated the moderately reduced neural fibers in the periphery nerves. Urinary amino acid analysis showed increased levels of multiple neutral amino acids. Moreover, muscle strengths in the lower limbs and the walking ability have been improved in both cases (MRC 3/5 to 4/5 in Patient 1; walking distance elongated from 50 to 100 m in Patient 2) after the treatment with oral nicotinic acid and intravenous injection of multiple amino acids. Exome sequencing revealed and confirmed the existence of the novel compound heterozygous SLC6A19 mutations: c.533G>A (p.Arg178Gln) and c.1379-1G>C mutations in patient1, and c.1433delG (p.Gly478AlafsTer44) and c.811G>A (p.Ala271Thr) in patient 2. Taken together, these findings expanded the clinical, neuroimaging, pathology, and genetic spectrum of Hartnup disease. However, the co-existence of HSP and peripheral neuropathy was only inferred based on clinical observations, and pathological and molecular studies are needed to further dissect the underlying mechanisms.

Non-Destructive Testing of Alfalfa Seed Vigor Based on Multispectral Imaging Technology.

Seed vigor is an important index to evaluate seed quality in plant species. How to evaluate seed vigor quickly and accurately has always been a serious problem in the seed research field. As a new physical testing method, multispectral technology has many advantages such as high sensitivity and accuracy, nondestructive and rapid application having advantageous prospects in seed quality evaluation. In this study, the morphological and spectral information of 19 wavelengths (365, 405, 430, 450, 470, 490, 515, 540, 570, 590, 630, 645, 660, 690, 780, 850, 880, 940, 970 nm) of alfalfa seeds with different level of maturity and different harvest periods (years), representing different vigor levels and age of seed, were collected by using multispectral imaging. Five multivariate analysis methods including principal component analysis (PCA), linear discriminant analysis (LDA), support vector machine (SVM), random forest (RF) and normalized canonical discriminant analysis (nCDA) were used to distinguish and predict their vigor. The results showed that LDA model had the best effect, with an average accuracy of 92.9% for seed samples of different maturity and 97.8% for seed samples of different harvest years, and the average sensitivity, specificity and precision of LDA model could reach more than 90%. The average accuracy of nCDA in identifying dead seeds with no vigor reached 93.3%. In identifying the seeds with high vigor and predicting the germination percentage of alfalfa seeds, it could reach 95.7%. In summary, the use of Multispectral Imaging and multivariate analysis in this experiment can accurately evaluate and predict the seed vigor, seed viability and seed germination percentages of alfalfa, providing important technical methods and ideas for rapid non-destructive testing of seed quality.

The Transcriptome of Cunninghamia lanceolata male/female cone reveal the association between MIKC MADS-box genes and reproductive organs development.

BACKGROUND: Cunninghamia lanceolata (Chinese fir), a member of the conifer family Cupressaceae, is one of the most popular cultivated trees for wood production in China. Continuous research is being performed to improve C. lanceolata breeding values. Given the high rate of seed abortion (one of the reasons being the failure of ovule and pollen development) in C. lanceolata, the proper formation of female/male cones could theoretically increase the number of offspring in future generations. MIKC MADS-box genes are well-known for their roles in the flower/cone development and comprise the typical/atypical floral development model for both angiosperms and gymnosperms. RESULTS: We performed a transcriptomic analysis to find genes differentially expressed between female and male cones at a single, carefully determined developmental stage, focusing on the MIKC MADS-box genes. We finally obtained 47 unique MIKC MADS-box genes from C. lanceolata and divided these genes into separate branches. 27 out of the 47 MIKC MADS-box genes showed differential expression between female and male cones, and most of them were not expressed in leaves. Out of these 27 genes, most B-class genes (AP3/PI) were up-regulated in the male cone, while TM8 genes were up-regulated in the female cone. Then, with no obvious overall preference for AG (class C + D) genes in female/male cones, it seems likely that these genes are involved in the development of both cones. Finally, a small number of genes such as GGM7, SVP, AGL15, that were specifically expressed in female/male cones, making them candidate genes for sex-specific cone development. CONCLUSIONS: Our study identified a number of MIKC MADS-box genes showing differential expression between female and male cones in C. lanceolata, illustrating a potential link of these genes with C. lanceolata cone development. On the basis of this, we postulated a possible cone development model for C. lanceolata. The gene expression library showing differential expression between female and male cones shown here, can be used to discover unknown regulatory networks related to sex-specific cone development in the future.

Dynamic growth models for Caragana korshinskii shrub biomass in China.

The Caragana korshinskii shrub is a widely distributed plant found in arid regions and plays an important role in ecological environment protection. Accurate estimations of shrub biomass are particularly important for natural resource management decision making. 114 individual C. korshinskii shrubs from three regions were collected in northwest China in this study. With regions as fixed (dummy variables) and random effects, the nonlinear least square (NLS) regression approach, nonlinear fixed effects (NLFE) approach and nonlinear mixed effects (NLME) approach were developed to predict dynamic growth of total, aboveground, stem, foliage, and root biomass values of C. korshinskii shrub based on logistic function. Results revealed that both NLFE and NLME models performed better than NLS, which indicated that regions were important factors influenced shrub biomass dynamic growth. Additionally, NLME models had a smaller Bayesian information criterion (BIC) than NLFE models. For NLME models, the random effects of regions mainly influenced the growth rate and asymptotic value of the dynamic growth curve, and there was no significant influence on the values associated with the curve shape. Moreover, the modified NLME models with heteroscedasticity exhibited extremely significant differences (p < 0.0001) when compared to NLME models by the likelihood ratio (LR) test. The NLME models were proved to be an efficient approach for considering the random effects on shrub biomass dynamic growth and accounted for the heteroscedasticity of shrub biomass data.

The mediating role of intention of learning behaviour in learning behaviour.

Improving the quality of postgraduate study is one that must be addressed with the increase in the number of postgraduate students. This study aims to analyse the effects of learning attitude, learning motivation and self-efficacy on learning behaviour through the intention of learning behaviour, and the effect of learning behaviour on learning outcome. Measurements were made on 560 postgraduate students after the development of a scale. The scale was analysed for reliability and exploratory factor analysis using SPSS software. The date were then analysed using structural equation modelling (SEM) analysis techniques with path analysis and bootstrap methods. The results of the study showed that students' attitudes towards learning and self-efficacy had a significant indirect on learning behaviour through the mediating involvement of intention to learn behaviours, and learning behaviour had a significant effect on learning outcome. Therefore, there is a need to improve learning behaviour by improving students' intention to learn behaviour so that they can have good learning outcome.

microRNA-mRNA expression profiles in the skeletal muscle of myotonic dystrophy type 1.

OBJECTIVES: Myotonic dystrophy type 1 (DM1) is the most common muscular dystrophy in adults, yet there are currently no disease-modifying treatments. Disrupted miRNA expressions may lead to dysregulation of target mRNAs and dysfunction involved in DM1 pathogenic mechanism. METHODS: We used microarray platforms to examine the miRNA/mRNA expression profiles in skeletal muscle biopsies derived from DM1 patients and matched controls. Bioinformatics analysis and dual-luciferase reporter assay were conducted to provide insight into miRNA-mRNA regulatory networks altered in DM1. RESULTS: Twenty-three differentially expressed miRNAs and 135 differentially expressed genes were identified. qPCR confirmed that miR-3201, myogenic factor 5 (MYF5), myogenic differentiation 1 (MYOD1), CUGBP, Elav-like family member 1 (CELF1), and CELF2 were significantly up-regulated, while miR-196a, miR-200c, and miR-146a were significantly down-regulated. Enriched functions and pathways such as multicellular organismal development, RNA splicing, cell differentiation, and spliceosome are relevant to DM1. The miRNA-mRNA interaction network revealed that miR-182, miR-30c-2, and miR-200c were the critical nodes that potentially interacted with hub genes. Luciferase reporter assay confirmed the direct interaction between miR-196a and CELF2. CONCLUSION: Those results implied that the observed miRNA/mRNA dysregulation could contribute to specific functions and pathways related to DM1 pathogenesis, highlighting the dysfunction of miR-196a and CELF2.

PCDHA9 as a candidate gene for amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease. To identify additional genetic factors, we analyzed exome sequences in a large cohort of Chinese ALS patients and found a homozygous variant (p.L700P) in PCDHA9 in three unrelated patients. We generated Pcdhα9 mutant mice harboring either orthologous point mutation or deletion mutation. These mice develop progressive spinal motor loss, muscle atrophy, and structural/functional abnormalities of the neuromuscular junction, leading to paralysis and early lethality. TDP-43 pathology is detected in the spinal motor neurons of aged mutant mice. Mechanistically, we demonstrate that Pcdha9 mutation causes aberrant activation of FAK and PYK2 in aging spinal cord, and dramatically reduced NKA-α1 expression in motor neurons. Our single nucleus multi-omics analysis reveals disturbed signaling involved in cell adhesion, ion transport, synapse organization, and neuronal survival in aged mutant mice. Together, our results present PCDHA9 as a potential ALS gene and provide insights into its pathogenesis.

Coexistence of peripheral myelin protein 22 and dystrophin mutations in a chinese boy.

INTRODUCTION: We describe a 10-year-old Chinese boy with features of Charcot-Marie-Tooth disease (CMT) and Duchenne muscular dystrophy (DMD). METHODS: Case report. RESULTS: Weakness and mild sensory loss in the distal extremities, pes cavus, and nerve conduction findings suggested demyelinating neuropathy, while moderate calf pseudohypertrophy, proximal muscle weakness, a myopathic pattern on electromyography, and deficiency of dystrophin immunohistochemical staining on muscle biopsy indicated DMD. Genetic testing revealed a large deletion spanning exon 50 in the gene coding for dystrophin and duplications in the gene coding for peripheral myelin protein 22. CONCLUSIONS: This is an interesting and very rare case of CMT type 1A comorbid with DMD. This results in an unusual phenotype and rapid deterioration of motor function. Usage of both target region capture and next generation sequencing is a powerful tool for predicting precisely the range of the large DNA fragment deletion in DMD.

[Electrophysiological features of patients with myotonic dystrophy type 1].

OBJECTIVE: To explore the electromyography (EMG) and nerve conduction (NC) features of patients with myotonic dystrophy type 1 (DM1). METHODS: Routine PCR and triplet primed-PCR (TP-PCR) were performed for 33 clinically diagnosed DM1 cases at our clinic from June 2009 to June 2012. The EMG and NC results of 30 patients with a genetic diagnosis of DM1 were collected and analyzed. RESULTS: Myotonic discharges were found in all patients and EMG revealed myogenic changes in 29 patients. Among all 123 muscles examined, the incidence of myotonic discharges was, a little higher than that of myogenic changes (91.87% vs 90.24%). The rate of myotonic discharges in distal muscles was higher than that of myotonic discharges in proximal muscles (100% vs 83.61%). And the difference was statistically significant. No difference existed in myogenic changes between distal and proximal muscles.(87.10% vs 93.44%) Nerve conduction was all normal. CONCLUSIONS: Myotonic discharges and myogenic changes are important EMG features in DM1. In early stage of DM1, myotonic discharges may be the isolated EMG abnormality. Myotonic discharges are predominantly detected in distal muscles. The involved regions detected by EMG are wider than those of clinical findings. EMG is an important screening tool for subclinical or early atypical DM1 patients.

The complete chloroplast genome sequence of Astragalus melilotoides (Fabaceae), a leguminous forage in Northern China.

Astragalus melilotoides Pall. 1776 is a perennial leguminous forage, widely distributed in northern China, with cold, drought and disease resistance characteristics. Here, we determined the complete chloroplast (cp) genome sequence of A. melilotoides. It was 123,827 bp in length and 36.97% GC content with IR loss. The cp genome contained 110 complete genes, including 76 protein-coding genes, 30 tRNA genes, and four rRNA genes. A maximum likelihood (ML) phylogenetic tree revealed that A. melilotoides was related to A. americanus, A. gummifer, A. mongholicus, A. nakaianus, A. mongholicus var. nakaianus, and A. membranaceus var. membranaceus. The cp genome analysis of A. melilotoides will provide a reference for the phylogenetic study of Astragalus in the future.

Negative effects of phosphorus addition outweigh effects of arbuscular mycorrhizal fungi and nitrogen addition on grassland temporal stability in the eastern Eurasian desert steppe.

The temporal stability of grassland plant communities is substantially affected by soil nutrient enrichment. However, the potential main and interactive effects of arbuscular mycorrhizal fungi (AMF) and soil nitrogen (N) and phosphorus (P) enrichment on the stability of plant productivity have not yet been clarified. We combined a three-year in situ field experiment to assess the impacts of soil fertilization and AMF on the stability of plant productivity. P addition decreased the stability of plant productivity by increasing the standard deviation relative to the mean of plant productivity. However, compared to species richness, the stability of C3 grasses and other functional groups asynchrony were the most important drivers changing the stability of plant productivity. The negative impacts of P addition overrode the impacts of AMF on the stability of plant productivity. Overall, our study suggests the importance of soil nutrient availability over AMF in terms of shaping the stability of plant productivity. Our results also suggest that three-year anthropogenic soil nutrient enrichment could reduce the stability of plant communities in grassland regardless of AMF in the P-limited grassland ecosystem.

Responses of soil bacterial and fungal communities to altered precipitation in a desert steppe.

To investigate the response mechanisms of soil bacterial and fungal communities to the changes of preci-pitation in a desert steppe of Ningxia, we conducted a three-year precipitation control experiment following completely randomized design. There were five treatments, natural precipitation (T0), 50% less in precipitation (T1), 25% less in precipitation (T2), 25% more in precipitation (T3) and 50% more in precipitation (T4). By using Illumina high-throughput sequencing and bioinformatics analysis, we investigated the effects of increased and decreased precipitation on soil bacterial and fungal communities, and examined the correlations between soil physicochemical properties, plant communities and soil bacterial and fungal communities. The result showed that the richness of soil bacteria and fungi was highest in the T4 treatment. In addition, the relative abundance of Chloroflexi, the predominant phyla of soil bacteria was more sensitive to precipitation change. However, the relative abundance of only Ascomycota, a rare fungal taxon, responded to precipitation changes. Results of redundancy analysis showed that the first two axes accounted for 92.8% and 87.4% of the total variance for soil bacterial and fungal community composition, respectively. Precipitation and soil pH were the most important environmental factors driving changes in soil bacterial diversity and community composition. On the one hand, precipitation had a direct positive effect on bacterial diversity and community composition. On the other hand, precipitation changed pH by affecting soil moisture, which in turn had a significant indirect effect on bacterial diversity and community composition. Plant community biomass, plant species richness, and soil pH were the most influential environmental factors affecting fungal diversity and community composition. Precipitation had no direct effect on soil fungal community, but had a significant indirect effect by changing plant community richness and soil pH. The response mechanisms of bacterial and fungal communities in soil differed significantly under different precipitation regimes in the desert grasslands of Ningxia.

Applications of Machine Learning to Diagnosis of Parkinson's Disease.

BACKGROUND: Accurate diagnosis of Parkinson's disease (PD) is challenging due to its diverse manifestations. Machine learning (ML) algorithms can improve diagnostic precision, but their generalizability across medical centers in China is underexplored. OBJECTIVE: To assess the accuracy of an ML algorithm for PD diagnosis, trained and tested on data from different medical centers in China. METHODS: A total of 1656 participants were included, with 1028 from Beijing (training set) and 628 from Fuzhou (external validation set). Models were trained using the least absolute shrinkage and selection operator-logistic regression (LASSO-LR), decision tree (DT), random forest (RF), eXtreme gradient boosting (XGboost), support vector machine (SVM), and k-nearest neighbor (KNN) techniques. Hyperparameters were optimized using five-fold cross-validation and grid search techniques. Model performance was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve, accuracy, sensitivity (recall), specificity, precision, and F1 score. Variable importance was assessed for all models. RESULTS: SVM demonstrated the best differentiation between healthy controls (HCs) and PD patients (AUC: 0.928, 95% CI: 0.908-0.947; accuracy: 0.844, 95% CI: 0.814-0.871; sensitivity: 0.826, 95% CI: 0.786-0.866; specificity: 0.861, 95% CI: 0.820-0.898; precision: 0.849, 95% CI: 0.807-0.891; F1 score: 0.837, 95% CI: 0.803-0.868) in the validation set. Constipation, olfactory decline, and daytime somnolence significantly influenced predictability. CONCLUSION: We identified multiple pivotal variables and SVM as a precise and clinician-friendly ML algorithm for prediction of PD in Chinese patients.

Multidisciplinary molecular consultation increases the diagnosis of pediatric epileptic encephalopathy and neurodevelopmental disorders.

BACKGROUND: Epilepsy (EP) is a common neurological disease in which 70-80% are thought to have a genetic cause. In patients with epilepsy, neurodevelopmental delay (NDD) was prevalent. Next generation of sequencing has been widely used in diagnosing EP/NDD. However, the diagnostic yield remains to be 40%-50%. Many reanalysis pipelines and software have been developed for automated reanalysis and decision making for the diseases. Nevertheless, it is a highly challenging task for smaller genetic centers or a routine pediatric practice. To address the clinical and genetic "diagnostic odyssey," we organized a Multidisciplinary Molecular Consultation (MMC) team for molecular consultation for 202 children with EP/NDD patients referred by lower level hospitals. METHODS: All the patients had undergone an aligned and sequential consultations and discussions by a "triple reanalysis" procedure by clinical, genetic specialists, and researchers. RESULTS: Among the 202 cases for MMC, we totally identified 47 cases (23%) harboring causative variants in 24 genes and 15 chromosomal regions after the MMC. In the 15 cases with positive CNVs, 3 cases harbor the deletions or duplications in 16p11.2, and 2 cases for 1p36. The bioinformatical reanalysis revealed 47 positive cases, in which 12 (26%) were reported to be negative, VUS or incorrectly positive in pre-MMC reports. Additionally, among 87 cases with negative cases, 4 (5%) were reported to be positive in pre-MMC reports. CONCLUSION: We established a workflow allowing for a "one-stop" collaborative assessments by experts of multiple fields and helps for correct the diagnosis of cases with falsenegative and -positive and VUS genetic reports and may have significant influences for intervention, prevention and genetic counseling of pediatric epilepsy and neurodevelopmental disorders.