Electronic tongue (E-Tongue), as a novel taste analysis tool, shows a promising perspective for taste recognition. In this paper, we constructed a voltammetric E-Tongue system and measured 13 ...different kinds of liquid samples, such as tea, wine, beverage, functional materials, etc. Owing to the noise of system and a variety of environmental conditions, the acquired E-Tongue data shows inseparable patterns. To this end, from the viewpoint of algorithm, we propose a local discriminant preservation projection (LDPP) model, an under-studied subspace learning algorithm, that concerns the local discrimination and neighborhood structure preservation. In contrast with other conventional subspace projection methods, LDPP has two merits. On one hand, with local discrimination it has a higher tolerance to abnormal data or outliers. On the other hand, it can project the data to a more separable space with local structure preservation. Further, support vector machine, extreme learning machine (ELM), and kernelized ELM (KELM) have been used as classifiers for taste recognition in E-Tongue. Experimental results demonstrate that the proposed E-Tongue is effective for multiple tastes recognition in both efficiency and effectiveness. Particularly, the proposed LDPP-based KELM classifier model achieves the best taste recognition performance of 98%. The developed benchmark data sets and codes will be released and downloaded in http://www.leizhang.tk/ tempcode.html.
•A relatively inactive dynamic brain status occurred more often in SSNHL participants. Early-stage SSNHL participants showed decreased brain status transition number.•Disturbed neurovascular coupling ...restricted to the primary auditory cortex occurred in the intermediate- and late-stage SSNHL patients.•A significant shrinkage of the left medial superior frontal gyrus developed at the late stage.•Our study offered neuroimaging evidence for evolvement from functional to structural brain alterations of SSNHL patients with disease duration less than 1 month.
A cortical plasticity after long-duration single side deafness (SSD) is advocated with neuroimaging evidence while little is known about the short-duration SSDs. In this case-cohort study, we recruited unilateral sudden sensorineural hearing loss (SSNHL) patients and age-, gender-matched health controls (HC), followed by comprehensive neuroimaging analyses. The primary outcome measures were temporal alterations of varied dynamic functional network connectivity (dFNC) states, neurovascular coupling (NVC) and brain region volume at different stages of SSNHL. The secondary outcome measures were pure-tone audiograms of SSNHL patients before and after treatment. A total of 38 SSNHL patients (21 55% male; mean standard deviation age, 45.05 15.83 years) and 44 HC (28 64% male; mean standard deviation age, 43.55 12.80 years) were enrolled. SSNHL patients were categorized into subgroups based on the time from disease onset to the initial magnetic resonance imaging scan: early- (n = 16; 1-6 days), intermediate- (n = 9; 7-13 days), and late- stage (n = 13; 14-30 days) groups. We first identified slow state transitions between varied dFNC states at early-stage SSNHL, then revealed the decreased NVC restricted to the auditory cortex at the intermediate- and late-stage SSNHL. Finally, a significantly decreased volume of the left medial superior frontal gyrus (SFGmed) was observed only in the late-stage SSNHL cohort. Furthermore, the volume of the left SFGmed is robustly correlated with both disease duration and patient prognosis. Our study offered neuroimaging evidence for the evolvement from functional to structural brain alterations of SSNHL patients with disease duration less than 1 month, which may explain, from a neuroimaging perspective, why early-stage SSNHL patients have better therapeutic responses and hearing recovery.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Objective Recent studies have indicated that circular RNAs (circRNAs) might play important roles in various diseases. However, little is known about the functions of circRNAs in the skeletal ...system, and the role of circRNAs in the mechanism by which bone morphogenetic protein 2 (BMP2) promotes bone differentiation remains unknown. Here, we performed RNA-seq to analyze differential expression of circRNA during different osteoblast differentiation stages and investigated the relevant mechanisms. Materials and methods Alkaline phosphatase (ALP) staining and activity were performed to assess osteogenic differentiation in MC3T3-E1 cells. The expression of osteogenic markers in MC3T3-E1 cells and the differential expression levels of circRNAs were measured and validated by qRT-PCR. Osteogenic marker proteins were measured by western blot. RNA-seq was performed to detect differential expression of circRNAs during the osteogenic differentiation of MC3T3-E1 cells induced by BMP2. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and PANTHER pathway analyses were performed to predict the functions of differentially expressed circRNAs and potentially co-expressed target genes. The microRNA (miRNA) targets of the circRNAs and circRNA–miRNA interactions were predicted by miRanda. The circRNA–miRNA co-expression network was constructed based on the correlation analysis between the differentially expressed circRNAs and miRNAs. A graph of the circRNA–miRNA network was created using Cytoscape 3.01. Results The Cell Counting Kit 8 (CCK-8) assay showed that BMP2 promoted the proliferation of osteoblasts in vitro . Both the intracellular ALP content and activity were increased in BMP2-treated MC3T3-E1 cells. In addition, the mRNA and protein levels of the osteoblastic markers ALP, Sp7 transcription factor (SP7) and runt-related transcription factor 2 (RUNX2) were substantially up-regulated. In the present study, 158 circRNAs were differentially expressed by a fold-change ≥2.0, P < 0.05 and false discovery rate <0.05. Among these, 74 circRNAs were up-regulated, while 84 circRNAs were down-regulated. In addition, the expression levels of circRNA.5846, circRNA.19142 and circRNA.10042 were significantly increased in the BMP2 group. Furthermore, by analyzing the target mRNAs of miR-7067-5p using GO and PANTHER pathway analyses, circ19142 and circ5846 were found to be not only strongly associated with the biological process of the positive regulation of developmental processes but also related to the fibroblast growth factor, epidermal growth factor, platelet-derived growth factor and Wnt signaling pathways, which are involved in cell growth and differentiation. Conclusion The present study identified circ19142 and circ5846 as being associated with osteoblast differentiation and BMP2 may induce osteogenic differentiation through a circ19142/circ5846-targeted miRNA–mRNA axis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Type 2 diabetes mellitus (T2DM) is a significant risk factor for mild cognitive impairment (MCI) and the acceleration of MCI to dementia. The high glucose level induce disturbance of neurovascular ...(NV) coupling is suggested to be one potential mechanism, however, the neuroimaging evidence is still lacking. To assess the NV decoupling pattern in early diabetic status, 33 T2DM without MCI patients and 33 healthy control subjects were prospectively enrolled. Then, they underwent resting state functional MRI and arterial spin labeling imaging to explore the hub-based networks and to estimate the coupling of voxel-wise cerebral blood flow (CBF)-degree centrality (DC), CBF-mean amplitude of low-frequency fluctuation (mALFF) and CBF- mean regional homogeneity (mReHo). We further evaluated the relationship between NV coupling pattern and cognitive performance (false discovery rate corrected). T2DM without MCI patients displayed significant decrease in the absolute CBF-mALFF, CBF-mReHo coupling of CBFnetwork and in the CBF-DC coupling of DCnetwork. Besides, networks which involved CBF and DC hubs mainly located in the default mode network (DMN). Furthermore, less severe disease and better cognitive performance in T2DM patients were significantly correlated with higher coupling of CBF-DC, CBF-mALFF or CBF-mReHo, especially for the cognitive dimensions of general function and executive function. Thus, coupling of CBF-DC, CBF-mALFF and CBF-mReHo may serve as promising indicators to reflect NV coupling state and to explain the T2DM related early cognitive impairment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
: To investigate the white matter (WM) integrity and hippocampal functional connectivity (FC) in type 2 diabetes mellitus (T2DM) patients without mild cognitive impairment (MCI) by using diffusion ...tensor imaging (DTI) and resting-state functional magnetic resonance imaging (rs-fMRI), respectively.
: Twelve T2DM patients without MCI and 24 age, sex and education matched healthy controls (HC) were recruited. DTI and rs-fMRI data were subsequently acquired on a 3.0T MR scanner. Tract-based spatial statistics (TBSS) combining region of interests (ROIs) analysis was used to investigate the alterations of DTI metrics (fractional anisotropy (FA), mean diffusivity (MD), λ
and λ
) and FC measurement was performed to calculate hippocampal FC with other brain regions. Cognitive function was evaluated by using Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Brain volumes were also evaluated among these participants.
: There were no difference of MMSE and MoCA scores between two groups. Neither whole brain nor regional brain volume decrease was revealed in T2DM patients without MCI. DTI analysis revealed extensive WM disruptions, especially in the body of corpus callosum (CC). Significant decreases of hippocampal FC with certain brain structures were revealed, especially with the bilateral frontal cortex. Furthermore, the decreased FA in left posterior thalamic radiation (PTR) and increased MD in the splenium of CC were closely related with the decreased hippocampal FC to caudate nucleus and frontal cortex.
: T2DM patients without MCI showed extensive WM disruptions and abnormal hippocampal FC. Moreover, the WM disruptions and abnormal hippocampal FC were closely associated.
-T2DM patients without MCI demonstrated no obvious brain volume decrease.-Extensive white matter disruptions, especially within the body of corpus callosum, were revealed with DTI analysis among the T2DM patients.-Despite no MCI in T2DM patients, decreased functional connectivity between hippocampal region and some critical brain regions were detected.-The alterations in hippocampal functional connectivity were closely associated with those of the white matter structures in T2DM patients. This trial was registered to ClinicalTrials.gov (NCT02420470, https://www.clinicaltrials.gov/).
Extreme learning machine (ELM) is a popular method in machine learning with extremely few parameters, fast learning speed and model efficiency. Unsupervised feature learning based ELM receives rising ...research focus. Recently the ELM auto-encoder (ELM-AE) was proposed for this task, which develops the ELM based compact feature learning without sacrificing elegant solution. Compared with ELM-AE and following
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-regularized ELM-AE, we introduce a sparse Bayesian learning scheme into ELM-AE for better generalization capability. A parallel training strategy is also integrated to improve time-efficiency of multi-output sparse Bayesian learning. Furthermore, pruning hidden nodes for better performance and efficiency according to estimated variances of prior distribution of output weights is achieved. Experiments on several datasets verify the effectiveness and efficiency of our proposed ELM-AE for unsupervised feature learning, compared with PCA, NMF, ELM-AE and
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-regularized ELM-AE.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Uniparental-inherited haploid genetic marker of Ychromosome single nucleotide polymorphisms (Y-SNP) have the power to provide a deep understanding of the human evolutionary past, forensic pedigree, ...and bio-geographical ancestry information. Several international cross-continental or regional Y-panels instead of Y-whole sequencing have recently been developed to promote Y-tools in forensic practice. However, panels based on next-generation sequencing (NGS) explicitly developed for Chinese populations are insufficient to represent the Chinese Y-chromosome genetic diversity and complex population structures, especially for Chinese-predominant haplogroup O. We developed and validated a 639-plex panel including 633 Y-SNPs and 6 Y-Insertion/deletions, which covered 573 Y haplogroups on the Y-DNA haplogroup tree. In this panel, subgroups from haplogroup O accounted for 64.4% of total inferable haplogroups. We reported the sequencing metrics of 354 libraries sequenced with this panel, with the average sequencing depth among 226 individuals being 3,741x. We illuminated the high level of concordance, accuracy, reproducibility, and specificity of the 639-plex panel and found that 610 loci were genotyped with as little as 0.03 ng of genomic DNA in the sensitivity test. 94.05% of the 639 loci were detectable in male-female mixed DNA samples with a mix ratio of 1:500. Nearly all of the loci were genotyped correctly when no more than 25 ng/muL tannic acid, 20 ng/muL humic acid, or 37.5 muM hematin was added to the amplification mixture. More than 80% of genotypes were obtained from degraded DNA samples with a degradation index of 11.76. Individuals from the same pedigree shared identical genotypes in 11 male pedigrees. Finally, we presented the complex evolutionary history of 183 northern Chinese Hans and six other Chinese populations, and found multiple founding lineages that contributed to the northern Han Chinese gene pool. The 639-plex panel proved an efficient tool for Chinese paternal studies and forensic applications.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Delayed passage of meconium or constipation during the perinatal period is traditionally regarded as a signal to initiate further work up to evaluate for serious diagnoses such as Hirschsprung’s ...disease (HD), meconium ileus due to Cystic Fibrosis, etc. The diagnosis of HD particularly warrants invasive testing to confirm the diagnosis, such as anorectal manometry or rectal suction biopsy. What if there was another etiology of perinatal constipation, that is far lesser known? Cow’s milk protein allergy (CMPA) is often diagnosed in infants within the first few weeks of life, however, there are studies that show that the CMPA allergen can be passed from mother to an infant in-utero, therefore allowing symptoms to show as early as day one of life. The presentation is more atypical, with perinatal constipation rather than with bloody stools, diarrhea, and vomiting. The diagnosis and management would be avoidance of cow's milk protein within the diet, with results and symptom improvement in patients immediately. Therefore, we discuss whether an alternative pathway to address perinatal constipation should be further discussed and implemented to potentially avoid invasive techniques in patients. This entails first ruling out CMPA with safe, noninvasive techniques with diet modification, and if unsuccessful, then moving forward with further diagnostic modalities.
•Nitric oxide inhibits EMP-TCA pathway via reducing HXK, PGI, PDH and SDH activities.•Nitric oxide reduces ETC by inhibiting NAD(H), CCO and SDH but rising NADH/NAD.•Nitric oxide increased PPP as ...NADK activity and NADP(H) contents were improved.•Nitric oxide-regulated respiratory pathways led to delayed cottony softening.•PGI, CS, SDH and CCO might be key factors in the nitric oxide-inhibited respiration.
This study investigated the impacts of nitric oxide (NO) fumigation on the respiratory metabolism of postharvest wax apple fruit and its impact on fruit cottony softening. NO treatment inhibited the respiration rate of wax apple fruit and delayed the development of cottony softening; NO treatment suppressed the activities of hexokinase, phosphohexose isomerase (PGI), pyruvate dehydrogenase, and succinate dehydrogenase (SDH) in fruit pulp, but improved the activities of pyruvate kinase and citrate synthase (CS), and maintained the contents of glucose and pyruvic acid, indicating a reduction in the EMP-TCA pathway. Moreover, the NADH content and the activities of SDH and cytochrome C oxidase (CCO) were decreased with NO treatment, while the NADH/NAD ratio increased, suggesting that the electron transport chain complexes of wax apple fruit were reduced. Besides, NO treatment enhanced the activity of NADK in wax apple fruit, which lowered the levels of NAD and NADH but increased levels of NADP and NADPH, indicating an increase in pentose phosphate pathway. Additionally, CATPCA and heatmap analysis show that the PGI, CS, SDH, and CCO played a crucial role in NO-inhibited respiration. Collectively, these findings indicate that NO treatment suppressed the respiratory metabolism of postharvest wax apple fruit via regulating respiratory pathways, which reduces fruit senescence and delays cottony softening.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
IMPORTANCE: Intravenous thrombolysis is increasingly used in patients with minor stroke, but its benefit in patients with minor nondisabling stroke is unknown. OBJECTIVE: To investigate whether dual ...antiplatelet therapy (DAPT) is noninferior to intravenous thrombolysis among patients with minor nondisabling acute ischemic stroke. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, open-label, blinded end point, noninferiority randomized clinical trial included 760 patients with acute minor nondisabling stroke (National Institutes of Health Stroke Scale NIHSS score ≤5, with ≤1 point on the NIHSS in several key single-item scores; scale range, 0-42). The trial was conducted at 38 hospitals in China from October 2018 through April 2022. The final follow-up was on July 18, 2022. INTERVENTIONS: Eligible patients were randomized within 4.5 hours of symptom onset to the DAPT group (n = 393), who received 300 mg of clopidogrel on the first day followed by 75 mg daily for 12 (±2) days, 100 mg of aspirin on the first day followed by 100 mg daily for 12 (±2) days, and guideline-based antiplatelet treatment until 90 days, or the alteplase group (n = 367), who received intravenous alteplase (0.9 mg/kg; maximum dose, 90 mg) followed by guideline-based antiplatelet treatment beginning 24 hours after receipt of alteplase. MAIN OUTCOMES AND MEASURES: The primary end point was excellent functional outcome, defined as a modified Rankin Scale score of 0 or 1 (range, 0-6), at 90 days. The noninferiority of DAPT to alteplase was defined on the basis of a lower boundary of the 1-sided 97.5% CI of the risk difference greater than or equal to −4.5% (noninferiority margin) based on a full analysis set, which included all randomized participants with at least 1 efficacy evaluation, regardless of treatment group. The 90-day end points were assessed in a blinded manner. A safety end point was symptomatic intracerebral hemorrhage up to 90 days. RESULTS: Among 760 eligible randomized patients (median IQR age, 64 57-71 years; 223 31.0% women; median IQR NIHSS score, 2 1-3), 719 (94.6%) completed the trial. At 90 days, 93.8% of patients (346/369) in the DAPT group and 91.4% (320/350) in the alteplase group had an excellent functional outcome (risk difference, 2.3% 95% CI, −1.5% to 6.2%; crude relative risk, 1.38 95% CI, 0.81-2.32). The unadjusted lower limit of the 1-sided 97.5% CI was −1.5%, which is larger than the −4.5% noninferiority margin (P for noninferiority <.001). Symptomatic intracerebral hemorrhage at 90 days occurred in 1 of 371 participants (0.3%) in the DAPT group and 3 of 351 (0.9%) in the alteplase group. CONCLUSIONS AND RELEVANCE: Among patients with minor nondisabling acute ischemic stroke presenting within 4.5 hours of symptom onset, DAPT was noninferior to intravenous alteplase with regard to excellent functional outcome at 90 days. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03661411
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