Search

Abstract Deep phenotyping can enhance the power of genetic analysis, including genome-wide association studies (GWAS), but the occurrence of missing phenotypes compromises the potential of such resources. Although many phenotypic imputation methods have been developed, the accurate imputation of millions of individuals remains challenging. In the present study, we have developed a multi-phenotype imputation method based on mixed fast random forest (PIXANT) by leveraging efficient machine learning (ML)-based algorithms. We demonstrate by extensive simulations that PIXANT is reliable, robust and highly resource-efficient. We then apply PIXANT to the UKB data of 277,301 unrelated White British citizens and 425 traits, and GWAS is subsequently performed on the imputed phenotypes, 18.4% more GWAS loci are identified than before imputation (8710 vs 7355). The increased statistical power of GWAS identified some additional candidate genes affecting heart rate, such as RNF220, SCN10A, and RGS6, suggesting that the use of imputed phenotype data from a large cohort may lead to the discovery of additional candidate genes for complex traits.

Nuclear protein delivery underlies an array of biotechnological and therapeutic applications. While many variations of protein delivery methods have been described, it can still be difficult or inefficient to introduce exogenous proteins into plants. A major barrier to progress is the cell wall which is primarily composed of polysaccharides and thus only permeable to small molecules. Here, we report a partial enzymatic cell wall digestion-mediated uptake method that efficiently delivers protein into the nucleus of plant cells. Such a method allowed efficient nuclear delivery of green fluorescent protein (GFP) flanked by two nuclear localization sequences (NLS) into Arabidopsis thaliana epidermal root cells without the usual need for large doses of nanoparticles or tissue cultures. We also show that switching from daylight to far-red light-grown conditions promotes effective protein penetration into deep cell layers. This study establishes that a partial enzymatic cell wall degradation could be applied to other cell organelles by changing the localization sequence, paving the way toward the rational engineering of plants.

Abstract Background Whole genome variants offer sufficient information for genetic prediction of human disease risk, and prediction of animal and plant breeding values. Many sophisticated statistical methods have been developed for enhancing the predictive ability. However, each method has its own advantages and disadvantages, so far, no one method can beat others. Results We herein propose an Ensemble Learning method for Prediction of Genetic Values (ELPGV), which assembles predictions from several basic methods such as GBLUP, BayesA, BayesB and BayesCπ, to produce more accurate predictions. We validated ELPGV with a variety of well-known datasets and a serious of simulated datasets. All revealed that ELPGV was able to significantly enhance the predictive ability than any basic methods, for instance, the comparison p-value of ELPGV over basic methods were varied from 4.853E−118 to 9.640E−20 for WTCCC dataset. Conclusions ELPGV is able to integrate the merit of each method together to produce significantly higher predictive ability than any basic methods and it is simple to implement, fast to run, without using genotype data. is promising for wide application in genetic predictions.

Chinese cabbage is an economically important Brassica vegetable worldwide, and clubroot, which is caused by the soil-borne protist plant pathogen Plasmodiophora brassicae is regarded as a destructive disease to Brassica crops. Previous studies on the gene transcripts related to Chinese cabbage resistance to clubroot mainly employed RNA-seq technology, although it cannot provide accurate transcript assembly and structural information. In this study, PacBio RS II SMRT sequencing was used to generate full-length transcriptomes of mixed roots at 0, 2, 5, 8, 13, and 22 days after P. brassicae infection in the clubroot-resistant line DH40R. Overall, 39 376 high-quality isoforms and 26 270 open reading frames (ORFs) were identified from the SMRT sequencing data. Additionally, 426 annotated long noncoding RNAs (lncRNAs), 56 transcription factor (TF) families, 1 883 genes with poly(A) sites and 1 691 alternative splicing (AS) events were identified. Furthermore, 1 201 of the genes had at least one AS event in DH40R. A comparison with RNA-seq data revealed six differentially expressed AS genes (one for disease resistance and five for defensive response) that are potentially involved in P. brassicae resistance. The results of this study provide valuable resources for basic research on clubroot resistance in Chinese cabbage.

Abstract Background Accumulating data indicate that N6-methyladenosine (m6A) RNA methylation and lncRNA deregulation act crucial roles in cancer progression. Heterogeneous nuclear ribonucleoprotein A2B1 (HNRNPA2B1) as an m6A “reader” has been reported to be an oncogene in multiple malignancies. We herein aimed to elucidate the role and underlying mechanism by which HNRNPA2B1-mediated m6A modification of lncRNAs contributes to non-small cell lung cancer (NSCLC). Methods The expression levels of HNRNPA2B1 and their association with the clinicopathological characteristics and prognosis in NSCLC were determined by RT-qPCR, Western blot, immunohistochemistry and TCGA dataset. Then, the role of HNRNPA2B1 in NSCLC cells was assessed by in vitro functional experiments and in vivo tumorigenesis and lung metastasis models. HNRNPA2B1-mediated m6A modification of lncRNAs was screened by m6A-lncRNA epi-transcriptomic microarray and verified by methylated RNA immunoprecipitation (Me-RIP). The lncRNA MEG3-specific binding with miR-21-5p was evaluated by luciferase gene report and RIP assays. The effects of HNRNPA2B1 and (or) lncRNA MEG3 on miR-21-5p/PTEN/PI3K/AKT signaling were examined by RT-qPCR and Western blot analyses. Results We found that upregulation of HNRNPA2B1 was associated with distant metastasis and poor survival, representing an independent prognostic factor in patients with NSCLC. Knockdown of HNRNPA2B1 impaired cell proliferation and metastasis in vitro and in vivo, whereas ectopic expression of HNRNPA2B1 possessed the opposite effects. Mechanical investigations revealed that lncRNA MEG3 was an m6A target of HNRNPA2B1 and inhibition of HNRNPA2B1 decreased MEG3 m6A levels but increased its mRNA levels. Furthermore, lncRNA MEG3 could act as a sponge of miR-21-5p to upregulate PTEN and inactivate PI3K/AKT signaling, leading to the suppression of cell proliferation and invasion. Low expression of lncRNA MEG3 or elevated expression of miR-21-5p indicated poor survival in patients with NSCLC. Conclusions Our findings uncover that HNRNPA2B1-mediated m6A modification of lncRNA MEG3 promotes tumorigenesis and metastasis of NSCLC cells by regulating miR-21-5p/PTEN axis and may provide a therapeutic target for NSCLC.

Owing to the poor cold tolerance of Stenotaphrum Trin and the urgent need for shade-tolerant grass species in temperate regions of East China, this study evaluated the cold tolerance of 55 Stenotaphrum accessions, aiming to provide shade-tolerant materials for temperate regions. A fine cold-tolerant turfgrass should have both the advantages of delayed fall dormancy and early spring green-up. However, previous research on the cold resistance of turfgrass has mainly focused on the performance of the spring green-up, with less attention paid to the fall dormancy, which has affected the ornamental and application value of turfgrass. This study first dynamically investigated the leaf colour of each accession during the fall dormancy and the coverage during the spring green-up and evaluated the cold resistance of the accession through membership functions and cluster analysis. Significant differences in the cold resistance were found with the assignment of breeding lines to four categories. The weak correlation (R2 = 0.1682) between leaf colour during the fall dormancy and coverage during the spring green-up indicates that using the performance of a single period to represent the cold resistance of accessions is not appropriate. To test whether using the laboratory-based LT50 and stolon regrowth rating analysis can replace the above-improved method, we conducted a related analysis and found that the fit between these two methods is very poor. This phenomenon is attributed to the poor correlation between the laboratory-based parameters and the pot-investigated data. Therefore, this study presents a cold resistance evaluation method for Stenotaphrum that integrates performance in both the fall dormancy and spring green-up periods. This improved evaluation method cannot be simplified by the growth performance of a single period or replaced by using laboratory-based LT50 and stolon regrowth tests. With the help of this improved method, several excellent cold tolerance accessions (ST003, S13, and S12) were identified for temperate regions of East China.

Abstract Background Genetic variation in regulatory sequences that alter transcription factor (TF) binding is a major cause of phenotypic diversity. Brassinosteroid is a growth hormone that has major effects on plant phenotypes. Genetic variation in brassinosteroid-responsive cis-elements likely contributes to trait variation. Pinpointing such regulatory variations and quantitative genomic analysis of the variation in TF-target binding, however, remains challenging. How variation in transcriptional targets of signaling pathways such as the brassinosteroid pathway contributes to phenotypic variation is an important question to be investigated with innovative approaches. Results Here, we use a hybrid allele-specific chromatin binding sequencing (HASCh-seq) approach and identify variations in target binding of the brassinosteroid-responsive TF ZmBZR1 in maize. HASCh-seq in the B73xMo17 F1s identifies thousands of target genes of ZmBZR1. Allele-specific ZmBZR1 binding (ASB) has been observed for 18.3% of target genes and is enriched in promoter and enhancer regions. About a quarter of the ASB sites correlate with sequence variation in BZR1-binding motifs and another quarter correlate with haplotype-specific DNA methylation, suggesting that both genetic and epigenetic variations contribute to the high level of variation in ZmBZR1 occupancy. Comparison with GWAS data shows linkage of hundreds of ASB loci to important yield and disease-related traits. Conclusion Our study provides a robust method for analyzing genome-wide variations of TF occupancy and identifies genetic and epigenetic variations of the brassinosteroid response transcription network in maize.

Objective: Assessing carotid and radial pulses is an essential sphygmology method in traditional Chinese medicine (TCM). It is believed in TCM and by doctors that pulse force is markedly linked with the physiological state of a human, including body mass index (BMI) and temperature. However, comprehensive analysis elucidating these potential correlations remains undetermined. Therefore, this investigation aimed to assess the association of pulse strength with human metabolism. Materials and Methods: The mean blood flow velocity (MBFV) of the carotid artery and pulse force of 122 healthy adults included in this investigation were assessed using ultrasound and manual palpation. Their thermal texture map was also acquired. Results: No substantial variation was observed in the carotid arterial MBFV among normal individuals (P > 0.05) regardless of body side and gender. However, young individuals had higher blood velocity than middle-aged individuals (P < 0.05). Furthermore, it was identified that MBFV was negatively associated with BMI and torso temperature; however, it was positively linked with hand temperature. Conclusions: This investigation revealed that carotid arterial MBFV could indicate the physical state of humans, including BMI and temperature, and therefore, is valuable for elucidating the effect of TCM on yin–yang. The data validated some TCM beliefs and supported the implementation of sphygmology in TCM.

Abstract Wearable electronics, as essential components of the Internet of Things (IoT), have attracted widespread attention, and the trend is to configure attractive wearable smart microsystems by integrating sensing, powering, and other functions. Herein, we developed an elastic hybrid triboelectric–electromagnetic microenergy harvester (named EHTE) to realize hybrid sensing and microenergy simultaneously. This EHTE is a highly integrated triboelectric nanogenerator (TENG) and electromagnetic nanogenerator (EMG). Based on the triboelectric–electromagnetic hybrid mechanism, an enhanced electrical output of the EHTE was achieved successfully, which demonstrates the feasibility of the EHTE for microelectronics powering. Moreover, with the merits of the EMG, the developed hybrid microenergy harvester integrated both active frequency sensing and passive inductive sensing capabilities. Specifically, the almost linear correlation of the electromagnetic outputs to the frequencies of the external stimulus endowed the proposed EHTE with an outstanding active frequency sensing ability. In addition, due to the unique structural configuration of the EMG (i.e., a conductive permanent magnet (PM), hybrid deformation layer, and flexible printed circuit board (FPCB) coil), an opportunity was provided for the developed EHTE to serve as a passive inductive sensor based on the eddy current effect (i.e., a form of electromagnetic induction). Therefore, the developed EHTE successfully achieved the integration of hybrid sensing (i.e., active frequency sensing and passive inductive sensing) and microenergy (i.e., the combination of electromagnetic effect and triboelectric effect) within a single device, which demonstrates the potential of this newly developed EHTE for wearable electronic applications, especially in applications of compact active microsystems.

ObjectiveEnteral feeding after intestinal atresia has always been a concern for clinicians. But the present studies mainly focused on single factors. This research aimed to comprehensively analyze the multiple factors on complete enteral nutrition after primary anastomosis, and establish the convenient prediction model.MethodsWe retrospectively collected reliable information in neonates with intestinal atresia form January 2010 to June 2022. The cox regression analysis was performed to select independent risk factors and develop nomogram. Subsequently, ROC curve, calibration curve and decision curve were drawn to thoroughly evaluate the accuracy and applicability of the model.ResultsThe predictors finally included in the model were gestational age, meconium peritonitis, distance from the anastomosis to the ileocecal region, diameter ratio of proximal to distal bowels, and time of initial feeding. The nomogram of predicting the probability of week 2, week 3 and week 4 was drawn and their area under the curve were 0.765, 0.785 and 0.747, respectively. Similarly, calibration and decision curve indicated that the prediction model had a great prediction performance.ConclusionThe clinical value of predictive models can be recognized. The hope is that the predictive model can help pediatricians reduce hospital costs and parental anxiety.

Purpose: Pelvic fractures are characterized by high energy injuries and often accompanied with abdominal and pelvic organ injury. CT has been applied for several decades to evaluate blunt pelvic trauma patients. However, it has a certain rate of inaccurate diagnosis of abdominal hollow viscus injury (HVI), especially in the early stage after injury. The delayed diagnosis of HVI could result in a high morbidity and mortality. The bowel injury prediction score (BIPS) applied 3 clinical variables to determine whether an early surgical intervention for blunt HVI was necessary. We recently found another clinical variable (iliac ecchymosis, IE) which appeared at the early stage of injury, could be predicted for HVI. The main objective of this study was to explore the novel combination of IE and BIPS to enhance the early diagnosis rate of HVI, and thus reduce complications and mortalities. Methods: We conducted a retrospective analysis from January 2008 to December 2018 and recorded blunt pelvic trauma patients in our hospital. The inclusion criteria were patients who were verified with pelvic fractures using abdomen and pelvis CT scan in the emergency department before any surgical intervention. The exclusion criteria were abdominal CT insufficiency before operation, abdominal surgery before CT scan, and CT mesenteric injury grade being 5. The MBIPS was defined as BIPS plus IE, which was calculated according to 4 variables: white blood cell counts of 17.0 or greater, abdominal tenderness, CT scan grade for mesenteric injury of 4 or higher, and the location of IE. Each clinical variable counted 1 score, totally 4 scores. The location and severity of IE was also noted. Results: In total, 635 cases were hospitalized and 62 patients were enrolled in this study. Of these included patients, 77.4% (40 males and 8 females) were operated by exploratory laparotomy and 22.6% (8 males and 6 females) were treated conservatively. In the 48 patients underwent surgical intervention, 46 were confirmed with HVI (45 with IE and 1 without IE). In 46 patients confirmed without HVI, only 3 patients had IE and the rest had no IE. The sensitivity and specificity of IE in predicting HVI was calculated as 97.8% (45/46) and 81.3% (13/16), respectively. The median MBIPS score for surgery group was 2, while 0 for the conservative treatment group. The incidence of HVI in patients with MBIPS score ≥ 2 was significantly higher than that in patients with MBIPS score less than ≤ 2 (OR = 17.3, p < 0.001). Conclusion: IE can be recognized as an indirect sign of HVI because of the high sensitivity and specificity, which is a valuable sign for HVI in blunt pelvic trauma patients. MBIPS can be used to predict HVI in blunt pelvic trauma patients. When the MBIPS score is ≥ 2, HVI is strongly suggested.

ObjectiveThe purpose of this study was to establish a predictive model of postoperative fever in children with acute appendicitis through retrospective analysis, and the prediction ability of the model is demonstrated by model evaluation and external validation.MethodsMedical records information on children undergoing surgery for acute appendicitis within 2 years were retrospectively collected, prospective collection was performed for external validation in the next 3 months. The patients were divided into two groups according to whether the postoperative body temperature exceeded 38.5°C. Multivariate logistic regression analysis was used to determine independent risk factors and develop regression equations and nomogram. ROC curve, calibration curve and decision curve were made for model evaluation. Finally, the clinical implication of the prediction model was clarified by associating postoperative fever with prognosis.ResultsHigh risk factors of postoperative fever included in the prediction model were onset time (X1), preoperative temperature (X2), leukocyte count (X3), C-reactive protein (X4) and operation time (X5). The regression equation is logit (P) = 0.005X1+0.166X2+0.056X3+0.004X4+0.005X5-9.042. ROC curve showed that the area under the curve (AUC) of the training set was 0.660 (0.621, 0.699), and the AUC of the verification set was 0.712 (0.639, 0.784). The calibration curve suggested that the prediction probability was close to the actual probability. Decision curve analysis (DCA) showed that patients could benefit from clinician’s judgment. Furthermore, prognostic analysis showed children presenting with postoperative fever had the more duration of postoperative fever, hospitalization stays and cost, except for rehospitalization.ConclusionAll the results revealed that the model had good predictive ability. Pediatricians can calculate the probability of postoperative fever and make timely interventions to reduce pain for children and parents.

We have designed and synthesized a novel simple colorimetric fluorescent probe with aggregation-induced emission (AIE) properties. Probe 5-(4-(diphenylamine)phenyl) thiophen-2-formaldehyde W exhibited a turn-on fluorescent response to cyanide ion (CN−), which induces distinct visual color changes. Probe W exhibited a highly selective and sensitive ratiometric fluorescence response for the detection of CN− over a wide pH range (4–11) and in the presence of common interferents. The linear detection of CN− over the concentration range of 4.00–38.00 µM (R2 = 0.9916, RSD = 0.02) was monitored by UV-Vis absorption spectrometry (UV-Vis) with the limit of detection determined to be 0.48 µM. The linear detection of CN− over the concentration range of 8.00–38.00 µM was examined by fluorescence spectrophotometry (R2 = 0.99086, RSD = 0.031), and the detection limit was found to be 68.00 nM. The sensing mechanisms were confirmed by 1H NMR spectroscopic titrations, X-ray crystallographic analysis, and HRMS. Importantly, probe W was found to show rapid response, high selectivity, and sensitivity for cyanide anions in real water samples, over the range of 100.17∼100.86% in artificial lake water and 100.54∼101.64% in running water by UV-Vis absorption spectrometry, and over the range of 99.42∼100.71% in artificial lake water and 100.59∼101.17% in running water by fluorescence spectrophotometry. Importantly, this work provides a simple and effective approach which uses an economically cheap and uncomplicated synthetic route for the selective, sensitive, and quantitative detection of CN− ions in systems relevant to the environment and health.

N6-methyladenine (6mA) DNA modification has been detected in several eukaryotic organisms, in some of them, it plays important role in the regulation process of stress-resistance response. However, the genome-wide distribution patterns and potential functions of 6mA DNA modification in halophyte Seashore paspalum (Paspalum vaginatum) remain largely unknown. Here, we examined the 6mA landscape in the P. vaginatum genome by adopting single molecule real-time sequencing technology and found that 6mA modification sites were broadly distributed across the P. vaginatum genome. We demonstrated distinct 6mA methylation levels and 6mA distribution patterns in different types of transcription genes, which hinted at different epigenetic rules. Furthermore, the moderate 6mA density genes in P. vaginatum functionally correlated with stress resistance, which also maintained a higher transcriptional level. On the other hand, a specific 6mA distribution pattern in the gene body and near TSS was observed in gene groups with higher RNA expression, which maybe implied some kind of regularity between 6mA site distribution and the protein coding genes transcription was possible. Our study provides new insights into the association between 6mA methylation and gene expression, which may also contribute to key agronomic traits in P. vaginatum.

AtACINUS is an Arabidopsis homolog of a mammalian splicing regulator and previously found to be O-GlcNAcyated. Here Bi et al. characterize the interactors and targets of AtACINUS, show it is required for development and stress responses and provide evidence that its O-glycosylation affects alternative splicing.

Seashore paspalum (Paspalum vaginatum) is an important warm-season turfgrass distributed in tropical and coastal areas. It has excellent resistance to abiotic stresses, such as salinity, drought, and low temperature. However, the research on genetic diversity of local P. vaginatum collections from China is limited. In this study, the genetic diversity among 58 P. vaginatum accessions from four different provinces in China and four cultivars were assessed using simple sequence repeat (SSR) markers. The results indicated that a total of 45 alleles were detected by 19 polymorphic markers, with a range of 2 to 4 and an average of 2.4 alleles per marker. The genetic similarity coefficients between each pair of the 58 P. vaginatum accessions and four cultivars ranged from 0.51 to 1.00, with an average of 0.77. The range of variation of Shannon diversity index of each SSR marker was 0.047 to 1.075, with an average of 0.486. The polymorphic information content of each SSR marker varies from 0.016 to 0.577, with an average of 0.249. The results of cluster analysis and principal component analysis (PCA) showed that 58 P. vaginatum accessions and four cultivars were divided into four groups. These results provide the theoretical basis for the genetic diversity assessments and molecular marker–assisted breeding of P. vaginatum species.

Metabolic labeling using stable isotopes is widely used for the relative quantification of proteins in proteomic studies. In plants, metabolic labeling using 15N has great potential, but the associated complexity of data analysis has limited its usage. Here, we present the 15N stable-isotope labeled protein quantification workflow utilizing open-access web-based software Protein Prospector. Further, we discuss several important features of 15N labeling required to make reliable and precise protein quantification. These features include ratio adjustment based on labeling efficiency, median and interquartile range for protein ratios, isotope cluster pattern matching to flag incorrect monoisotopic peak assignment, and caching of quantification results for fast retrieval.

BackgroundSpinocerebellar ataxia type 3 (SCA3) is one of the most common hereditary neurodegenerative diseases. Postural control dysfunction is the main symptom of SCA3, and the proprioceptive system is a critical sensory component of postural control. Accordingly, proprioception quantification assessment is necessary in monitoring the progression of SCA3.ObjectiveWe aimed to quantitatively assess lower limb proprioception and investigate the relationship between proprioception and clinical characteristics in patients with SCA3.MethodsA total of 80 patients with SCA3 and 62 health controls were recruited, and their lower limb proprioception was measured using the Pro-kin system. Clinical characteristics of the SCA3 patients were collected. Multivariable linear regression was used to investigate potential affected factors for lower limb proprioception.ResultsWe found that the patients with SCA3 experience poorer lower limb proprioception characterized by significant impairment in the average trace error (ATE) and time to carry out the test time execution (TTE) compared to controls (P < 0.05). Moreover, there were significant differences in TTE between the right and left lower limbs (P < 0.05) of the patients. Regression analyses revealed that increasing age at onset (AAO) predicts poorer lower limb proprioception for both ATE (β = 2.006, P = 0.027) and TTE (β = 1.712, P = 0.043) and increasing disease duration predicts poorer lower limb proprioception for ATE (β = 0.874, P = 0.044). AAO (β = 0.328, P = 0.019) along with the expanded alleles (β = 0.565, P = 0.000) could affect the severity of ataxia. By contrast, ATE (β = 0.036, P = 0.800) and TTE (β = −0.025, P = 0.862) showed no significant predictors.ConclusionsLower limb proprioception in patients with SCA3 is significantly impaired when compared to healthy controls. Increasing AAO and disease duration are related to impaired lower limb proprioception.

The electrophysiological recording can be used to quantify the clinical features of central poststroke pain (CPSP) caused by different lesion locations. We aimed to explore the relationship between clinical features and lesion location in patients with CPSP using the current perception threshold (CPT) approach. Here, patients underwent the standardized CPT measure at five detection sites on both the contralesional and ipsilesional sides, using a constant alternating-current sinusoid waveform stimulus at three frequencies: 2000 Hz, 250 Hz, and 5 Hz. 57 CPSP patients were recruited in this cross-sectional study, including 13 patients with thalamic lesions and 44 patients with internal capsule lesions. Patients with a thalamic lesion had more frequent abnormal Aδ and C fibers than those with an internal capsule lesion (69.2% versus 36.4%, p value = 0.038; 53.8% versus 63.6%, p value = 0.038). The patients with internal capsule lesions had more frequent abnormal Aβ fibers than those with thalamic lesions (53.8% versus 63.6%, p value < 0.001). The sensory dysfunction in the patients with thalamic lesions was more likely to occur in the upper limbs (i.e., the shoulder (p value = 0.027) and the finger (p value = 0.040)). The lower limbs (i.e., the knee (p value = 0.040) and the toe (p value = 0.005)) were more likely to experience sensory dysfunction in the patients with internal capsule lesions. Hyperesthesia was more likely to occur in the thalamic patients, and hypoesthesia was more likely to occur in the patients with internal capsule lesions (p value < 0.001). In patients with thalamic lesions, Visual Analogue Scale (VAS) had a positive correlation with 5 Hz CPT on the shoulder (r=0.010, p value = 0.005), 250 Hz CPT on the finger (r=0.690, p value = 0.009) from the contralesional side, and 2000 Hz CPT on the knee (r=0.690, p value = 0.009). In patients with internal capsule lesions, VAS had a positive correlation with 2000 Hz CPT on the knee (r=0.312, p value = 0.039) and foot (r=0.538, p value < 0.001). In conclusion, the abnormal fiber types, sensory dysfunction territory, and clinical signs of CPSP in thalamic stroke differ from those in internal capsule stroke. Implementation of the portable and convenient CPT protocol may help clarify the locations of different stroke lesions in various clinical settings.

Objective. High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has been proposed as a promising therapeutic intervention for patients with disorders of consciousness (DOC). However, its therapeutic effects in the literature are inconsistently documented. The primary aim of this study was to explore the alterations in neural connectivity and neurobehavioral reactivity during rTMS modulation in patients with DOC. In addition, safety was investigated as a secondary aim. Methods. The presence of bilateral N20 components in DOC patients was determined by somatosensory-evoked potential (SEP) before enrollment in the study. A total of 64 patients were enrolled and randomly placed into the active and sham groups. Ultimately, 50 patients completed the study. Twenty-five patients in the active group underwent real HF-rTMS, and 25 patients in the sham group underwent sham HF-rTMS, which was delivered over the left dorsolateral prefrontal cortex (DLPFC). The outcome measures of performed pre- and postintervention included the latencies of the N20 and N20-P25 amplitudes of SEP, brainstem auditory-evoked potential (BAEP) grade, JFK Coma Recovery Scale-Revised (CRS-R) score, and Glasgow Coma Scale (GCS) score; any adverse events were recorded at any time during the intervention. Result. Following six weeks of treatment, a significant increase was observed in the total CRS-R and GCS scores, and the N20-P25 amplitudes of patients in the two groups were compared with that obtained from preintervention (all p values < 0.05). The waves of BAEP in the two groups also showed a trend toward normalized activity compared with preintervention grades (p values < 0.05). A significant decrease in the latencies of N20 (p values < 0.001) was observed in the active group compared with measurements obtained from preintervention, whereas no significant decrease was observed in the sham group (p values = 0.013). The improvement in total CRS-R scores (p values = 0.002), total GCS scores (p values = 0.023), and N20-P25 amplitudes (p values = 0.011) as well as the decrease in latencies of N20 (p values = 0.018) and change in BAEP grades (p values = 0.013) were significantly different between the two groups. The parameters in neural connectivity (N20-P25 amplitudes, N20 latencies, and BAEP grades) were significantly correlated with the total CRS-R and GCS scores at postintervention, and the changes of CRS-R before and after interventions have a positive relationship with N20-P25 amplitudes. No adverse events related to the rTMS protocol were recorded. Conclusion. Neural connectivity levels are affected by HF-rTMS and are significantly related to clinical responses in DOC patients with the presence of bilateral N20. The elevation of neural connectivity levels may lay a foundation for successful HF-rTMS treatment for DOC patients.

The cholinergic anti-inflammatory pathway (CAIP) has been proposed to regulate gastrointestinal inflammation via acetylcholine released from the vagus nerve activating α7 nicotinic receptor (α7nAChR) on macrophages. Parkinson’s disease (PD) patients and PD rats with substantia nigra (SN) lesions exhibit gastroparesis and a decayed vagal pathway. To investigate whether activating α7nAChR could ameliorate inflammation and gastric dysmotility in PD rats, ELISA, western blot analysis, and real-time PCR were used to detect gastric inflammation. In vitro and in vivo gastric motility was investigated. Proinflammatory mediator levels and macrophage numbers were increased in the gastric muscularis of PD rats. α7nAChR was located on the gastric muscular macrophages of PD rats. The α7nAChR agonists PNU-282987 and GTS-21 decreased nuclear factor κB (NF-κB) activation and monocyte chemotactic protein-1 mRNA expression in the ex vivo gastric muscularis of PD rats, and these effects were abolished by an α7nAChR antagonist. After treatment with PNU-282987 in vivo, the PD rats showed decreased NF-κB activation, inflammatory mediator production, and contractile protein expression and improved gastric motility. The present study reveals that α7nAChR is involved in the development of gastroparesis in PD rats and provides novel insight for the treatment of gastric dysmotility in PD patients.

By comprehensive first-principles calculations, we predict that monolayer Tl-based monochalcogenides TlX (X = S, Se, and Te) are a class of stable direct bandgap semiconductors with band edges lying at a pair of inequivalent valleys. The interplay between inversion symmetry breaking and spin-orbit coupling within active Tl-px,y and X-px,y states triggers robust spin-valley coupling, yielding sizable valley spin splittings in the conduction and valence bands with complete valley-contrasting physics under time-reversal symmetry. As a consequence, the valley and spin Hall effects naturally occur in the n- and p-doped TlX samples without any contamination from the other part of the Brillouin zone near the Fermi level. Also, valley polarization can be realized by the illumination of circularly polarized light with frequencies in the near-infrared and visible regions. These appealing physical properties and their strain sustainability together with feasible fabrication render monolayer TlX a competitive class of valleytronic materials for valley-based electronic and optoelectronic applications. [ABSTRACT FROM AUTHOR]

Abstract. Background:. In our previous paper, we demonstrated that Connexin 43 (CX43) was highly expressed in bladder cancer (BC) tissues. But the molecular mechanism about microRNAs (miRNAs) regulation upstream of CX43 in BC has not been well elucidated and remains to be further studied. MicroRNA-139-5p (miR-139-5p) is a tumor suppressor in progression of multifarious cancers including BC. Nevertheless, the underlying mechanisms of CX43/miR-139-5p in tumorigenesis of BC are still not well illustrated. The specific objective of our study was to inquiry the effect of CX43/miR-139-5p on BC progression and its underlying mechanism. Methods:. The bioinformatics analysis softwares were applied to predict the miRNAs in the upstream of CX43. First, the expression levels of miR-139-5p in BC tissues (tumor) and paracancer tissues (normal) were investigated using the data from The Cancer Genome Atlas database. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression level of miR-139-5p in three human BC cell lines 5637, T24, ECV-304 and a human bladder epithelial immortalized cell line SV-HUC-1 (normal control). Then si-CX43, si-control, miR-139-5p mimic, and its negative control (NC) were transfected into BC cell line ECV-304. The relationship of miR-139-5p and CX43 was analyzed by dual-luciferase reporter assay. The qRT-PCR and Western blotting were used to test the mRNA and protein expression level of CX43. The proliferation of ECV-304 and T24 cells were examined by cell counting kit-8. The migration and invasion of ECV-304 cells were tested by transwell assay. To determine whether miR-139-5p would affect cell proliferation, migration and invasion by targeting CX43, we executed the rescue assay. The comparison between two groups was analyzed by Student's t test, and comparisons among multiple samples were performed by one-way analysis of variance and a Bonferroni post hoc test. Results:. The expression of miR-139-5p was remarkably down-regulated in BC tissues (tumor vs. normal, 2.286 ± 0.017 vs. 3.211 ± 0.034, t = 11.540, P

Braconid parasitoids reared from Malus sieversii and Malus domestica trees in NW China infested by Agrilus mali Matsumura (Coleoptera, Buprestidae) are illustrated and discussed. Six species were found parasitising Agrilus mali in NW China, namely, Atanycolus ivanowi (Kokujev) (Braconinae), Doryctes undulatus (Ratzeburg), Pareucorystes varinervis Tobias, Polystenus rugosus Foerster, Spathius sinicus Chao, and Spathius brevicaudis Ratzeburg (Doryctinae). All listed species are newly recorded parasitoids of Agrilus mali. Pareucorystes varinervis and Spathius brevicaudis are new records for the Chinese fauna, but Spathius brevicaudis has been recorded from Taiwan before. Both sexes of Spathius brevicaudis are redescribed here to allow inclusion in the recent revision of the Chinese Spathius species. An identification key to the six braconid parasitoids of Agrilus mali in NW China is provided.

Abstract Background In clinical practice, a large number of post-stroke survivors require nasogastric tube (NGT) placement and nasal feeding for a relatively long period. However, its impact on the swallowing function remains largely unknown. This study examines the impact of prolonged placement of an NGT on the swallowing function of elderly post-stroke patients. Methods The participants of this study were 30 elderly post-stroke patients who had been using an NGT for more than 2 months. A videofluoroscopic swallowing study (VFSS) was performed before and 5 h after removal of the NGT. The following parameters were analyzed and compared, the functional dysphagia scale (FDS), residue in the valleculae, residue in the pyriform sinuses, and the penetration-aspiration scale (PAS). In addition, prior to the VFSS, the pharynx and larynx were examined using a fiberoptic laryngoscope. Results Significant differences were observed between the total scores of the FDS, pharyngeal transit times (PTTs), the residue in the valleculae, and the residue in the pyriform sinuses before and after the NGT removal, suggesting an improved swallowing function following the removal of the NGT. A significantly lower penetration-aspiration degree was found after removing the NGT compared with that before its removal. In addition, examinations using the fiberoptic laryngoscope showed that laryngopharyngeal edema was present in three quarters of the patients. Conclusions Our results demonstrate that prolonged placement of the NGT had a negative impact on the swallowing function of elderly post-stroke dysphagia patients, mainly on the pharyngeal phase.

Sugar, light, and hormones are major signals regulating plant growth and development, however, the interactions among these signals are not fully understood at the molecular level. Recent studies showed that sugar promotes hypocotyl elongation by activating the brassinosteroid (BR) signaling pathway after shifting Arabidopsis seedlings from light to extended darkness. Here, we show that sugar inhibits BR signaling in Arabidopsis seedlings grown under light. BR induction of hypocotyl elongation in seedlings grown under light is inhibited by increasing concentration of sucrose. The sugar inhibition of BR response is correlated with decreased effect of BR on the dephosphorylation of BZR1, the master transcription factor of the BR signaling pathway. This sugar effect is independent of the sugar sensors Hexokinase 1 (HXK1) and Target of Rapamycin (TOR), but requires the GSK3-like kinase Brassinosteroid-Insensitive 2 (BIN2), which is stabilized by sugar. Our study uncovers an inhibitory effect of sugar on BR signaling in plants grown under light, in contrast to its promotive effect in the dark. Such light-dependent sugar-BR crosstalk apparently contributes to optimal growth responses to photosynthate availability according to light-dark conditions.

Alzheimer’s disease (AD) is the most common form of dementia. Although the incidence of AD is high, the rates of diagnosis and treatment are relatively low. Moreover, effective means for the diagnosis and treatment of AD are still lacking. MicroRNAs (miRNAs, miRs) are non-coding RNAs that play regulatory roles by targeting mRNAs. The expression of miRNAs is conserved, temporal, and tissue-specific. Impairment of microRNA function is closely related to AD pathogenesis, including the beta-amyloid and tau hallmarks of AD, and there is evidence that the expression of some microRNAs differs significantly between healthy people and AD patients. These properties of miRNAs endow them with potential diagnostic and therapeutic value in the treatment of this debilitating disease. This review provides comprehensive information about the regulatory function of miRNAs in AD, as well as potential applications as diagnostic biomarkers.

Abstract Background Brassinosteroids (BRs) play a crucial role in plant vegetative growth and reproductive development. The transcription factors BZR1 and BES1/BZR2 are well characterized as downstream regulators of the BR signaling pathway in Arabidopsis and rice. Soybean contains four BZR1-like proteins (GmBZLs), and it was reported that GmBZL2 plays a conserved role in BR signaling regulation. However, the roles of other GmBZLs have not been thoroughly studied, and the targets of GmBZLs in soybean remain unclear. Results In this study, we first characterized GmBZL3 in soybean from gene expression patterns, conserved domains in coding sequences, and genomic replication times of four GmBZL orthologous. The results indicated that GmBZL3 might play conserved roles during soybean development. The overexpression of GmBZL3 P219L in the Arabidopsis BR-insensitive mutant bri1–5 partially rescued the phenotypic defects including BR-insensitivity, which provides further evidence that GmBZL3 functions are conserved between soybean and the homologous Arabidopsis genes. In addition, the identification of the GmBZL3 target genes through ChIP-seq technology revealed that BR has broad roles in soybean and regulates multiple pathways, including other hormone signaling, disease-related, and immunity response pathways. Moreover, the BR-regulated GmBZL3 target genes were further identified, and the results demonstrate that GmBZL3 is a major transcription factor responsible for BR-regulated gene expression and soybean growth. A comparison of GmBZL3 and AtBZR1/BES1 targets demonstrated that GmBZL3 might play conserved as well as specific roles in the soybean BR signaling network. Finally, the identification of two natural soybean varieties of the GmBZL3 mutantion by SNP analysis could facilitate the understanding of gene function during soybean development in the future. Conclusions We illustrate here that GmBZL3 orchestrates a genome-wide transcriptional response that underlies BR-mediated soybean early vegetative growth, and our results support that BRs play crucial regulatory roles in soybean morphology and gene expression levels.

Qian-Zheng-San, a traditional Chinese prescription consisting of Typhonii Rhizoma, Bombyx Batryticatus, Scorpio, has been found to play an active therapeutic role in central nervous system diseases. However, it is unclear whether Qian-Zheng-San has therapeutic value for peripheral nerve injury. Therefore, we used Sprague-Dawley rats to investigate this. A sciatic nerve crush injury model was induced by clamping the right sciatic nerve. Subsequently, rats in the treatment group were administered 2 mL Qian-Zheng-San (1.75 g/mL) daily as systemic therapy for 1, 2, 4, or 8 weeks. Rats in the control group were not administered Qian-Zheng-San. Rats in sham group did not undergo surgery and systemic therapy. Footprint analysis was used to assess nerve motor function. Electrophysiological experiments were used to detect nerve conduction function. Immunofluorescence staining was used to assess axon counts and morphological analysis. Immunohistochemical staining was used to observe myelin regeneration of the sciatic nerve and the number of motoneurons in the anterior horn of the spinal cord. At 2 and 4 weeks postoperatively, the sciatic nerve function index, nerve conduction velocity, the number of distant regenerated axons and the axon diameter of the sciatic nerve increased in the Qian-Zheng-San treatment group compared with the control group. At 2 weeks postoperatively, nerve fiber diameter, myelin thickness, and the number of motor neurons in the lumbar spinal cord anterior horn increased in the Qian-Zheng-San treatment group compared with the control group. These results indicate that Qian-Zheng-San has a positive effect on peripheral nerve regeneration.