Search

Predicting responsvienss to repetitive transcranial magnetic stimulation (rTMS) can facilitate personalized treatments with improved efficacy; however, predictive features related to this response are still lacking. We explored whether resting-state electroencephalography (rsEEG) functional connectivity measured at baseline or during treatment could predict the response to 10-day rTMS targeted to the right dorsolateral prefrontal cortex (DLPFC) in 36 patients with chronic insomnia disorder (CID). Pre- and post-treatment rsEEG scans and the Pittsburgh Sleep Quality Index (PSQI) were evaluated, with an additional rsEEG scan conducted after four rTMS sessions. Machine-learning approaches were employed to assess the ability of each connectivity measure to distinguish between responders (PSQI improvement > 25%) and non-responders (PSQI improvement ≤ 25%). Furthermore, we analyzed the connectivity trends of the two subgroups throughout the treatment. Our results revealed that the machine learning model based on baseline theta connectivity achieved the highest accuracy (AUC = 0.843) in predicting treatment response. Decreased baseline connectivity at the stimulated site was associated with higher responsiveness to TMS, emphasizing the significance of functional connectivity characteristics in rTMS treatment. These findings enhance the clinical application of EEG functional connectivity markers in predicting treatment outcomes.

Abstract Objective Sound touch elastography (STE) and sound touch quantification (STQ) are novel imaging methods to evaluate tissue stiffness. This study aims to investigate renal stiffness in patients with chronic kidney disease (CKD) by STE and STQ, using renal biopsy as ‘gold standard’. Methods Between 2019 January and 2022 June, 60 patients who underwent renal biopsy for proteinuria (cases) and 45 healthy volunteers (controls) at our hospital were included in this study. The maximum and mean elastic modulus (Emax, Emean) of region of interest in right kidney were measured by STE and STQ techniques. Biochemical profiles and renal biopsy findings were recorded. Results Both Emax and Emean measured by STE were significantly different between cases and controls. ROC analysis of STE measurements revealed using a cutoff of 13.53 kPa for Emax and 10.16 kPa for Emean, the area under the curve (AUC) to distinguish nephropathy from healthy was 0.718 and 0.744. Analysis of ROC for STQ measurements showed that using a cutoff value of 15.87 kPa for Emax and 9.95 kPa for Emean, the AUC for the nephropathy was 0.612 and 0.569. Emax and Emean values were significantly different among CKD patients with mild, moderate and severe pathological stage. The Emax value for STE was positively related to Scr, β2-MG (r = 0.257, 0.292, p

Wheat (Triticum aestivum L.) is one of the most important cereal crops worldwide, and its production is challenged by global climate change and a shortage of resources. The root system plays a vital role in uptaking water and nutrients and sensing soil environmental signals, and it has great potential to improve the final yield and stress tolerance of wheat. In order to further explore the genes regulating root development, this study focused on qRS-6D, located on chromosome 6D and spanning from 462,701,391 to 465,068,943, which was significantly associated with the total root length, root volume, root surface, and root fresh weight in our previous GWAS analysis. Firstly, its genetic effects were validated using an F6 segregating population by comparing the root-related traits of homologous lines harboring the alternative haplotypes of this QTL. Then, the number of causal genes of this QTL was narrowed down to four with a transcriptome-wide association study. Additionally, qRS-6D has been demonstrated to have genetic effects on several yield- (kernel length, kernel width, and thousand-kernel weight) and plant structure-related traits (plant height, peduncle length, total tiller number, productive tiller number, flag leaf length, and flag leaf angle). Relatively, the frequency of the favorable haplotype increased with the wheat breeding practice. This study provides a reliable genetic locus to improve root development and structure and evaluate its application potential in wheat breeding improvement.

Summary: Autophagy is a fundamental biological process critical to all eukaryotic cellular life. Although autophagy has been increasingly studied, how its process is precisely coordinated remains an open question. ATG14 (ATG14L/Barkor) is known to play a crucial role in both autophagosome formation and autophagosome-lysosome fusion. However, how ATG14 is regulated, especially at the post-translation level, is still not clear. Here, we report that MARCH7 (membrane-associated ring-CH-type finger 7), an E3 ubiquitin ligase, inhibits autophagy by ubiquitinating ATG14. MARCH7 significantly promotes K6-, K11-, and K63-linked mixed polyubiquitination on ATG14, triggering the aggregation of ATG14 and reducing its solubility in cells. Functionally, we find that MARCH7 depletion decreases the number of aggresome-like induced structures (ALISs). Mechanistically, we show that ubiquitinated ATG14 has fewer interactions with STX17, leading to the inhibition of autophagy flux. Collectively, our study reveals a mechanism in regulating autophagy and suggests a potential strategy for the treatment of autophagy-related diseases.

Introduction Idiopathic aplastic anaemia (IAA) is a heterogeneous autoimmune disease characterised by pancytopenia and bone marrow failure. The objective of the study was to investigate the clusters of lymphocyte subset in newly diagnosed IAA patients and explore their correlation with clinical characteristics.Methods A total of 124 newly diagnosed IAA patients were enrolled. Lymphocyte subset was detected by flow cytometry. Cluster analysis was conducted to identify subgroups of patients based on lymphocyte subset.Results Cluster analysis classified patients into four distinctive subgroups: Cluster 1 (CD4+ T cells dominant), Cluster 2 (CD8+ T cells dominant), Cluster 3 (NK cells dominant) and Cluster 4 (B cells dominant). Patients in Clusters 1 and 4 suffered more severe disease status than ones in Clusters 2 and 3 (p = .013). And with it, patients in Cluster 2 had the highest white blood cell count, haemoglobin level, reticulocyte count and reticulocyte percentage, while patients in Cluster 3 had the lowest lymphocyte percentage and the highest neutrophil count (all p

IntroductionPatients with aggressive lymphomas are at high risk of losing body resources, resulting in malnutrition, immunodeficiency and inferior outcomes. Nutritional status is closely associated with survival, but often neglected in the prognostic assessment. This study aimed to explore the significance of nutritional status in extranodal NK/T-cell lymphoma (ENKTL).MethodsUnivariate and multivariate Cox regression analyses were conducted to examine the significance of nutritional index on overall survival (OS) and progression-free survival (PFS). A nutrition-incorporated score system was constructed based on the multivariate results, and its calibration, discrimination and clinical utility were tested in the training and validation cohort.ResultsMultivariate analysis revealed controlling nutritional status (CONUT) score could independently predict OS (HR 10.247, P=0.001) and PFS (HR 5.587, P=0.001) in addition to prognostic index of natural killer lymphoma plus EBV (PINK-E). Herein, a reformative model, CONUT-PINK-E, was developed and further verified in external validation cohort. CONUT-PINK-E classified patients into three risk grades with significant survival differences (P < 0.001). Compared with the current models, CONUT-PINK-E presented superior discrimination, calibration and clinical benefit.DiscussionIn this study, we firstly verified that CONUT score was efficient to screen prognosis-related malnutrition in ENKTL. Moreover, we developed the first nutritional assessment-covered scoring system, CONUT-PINK-E, which might be a promising tool to provide references for clinical decision-making of ENKTL patients.

BackgroundRepetitive transcranial magnetic stimulation (rTMS) has been increasingly used as a treatment modality for chronic insomnia disorder (CID). However, our understanding of the mechanisms underlying the efficacy of rTMS is limited.ObjectiveThis study aimed to investigate rTMS-induced alterations in resting-state functional connectivity and to find potential connectivity biomarkers for predicting and tracking clinical outcomes after rTMS.MethodsThirty-seven patients with CID received a 10-session low frequency rTMS treatment applied to the right dorsolateral prefrontal cortex. Before and after treatment, the patients underwent resting-state electroencephalography recordings and a sleep quality assessment using the Pittsburgh Sleep Quality Index (PSQI).ResultsAfter treatment, rTMS significantly increased the connectivity of 34 connectomes in the lower alpha frequency band (8–10 Hz). Additionally, alterations in functional connectivity between the left insula and the left inferior eye junction, as well as between the left insula and medial prefrontal cortex, were associated with a decrease in PSQI score. Further, the correlation between the functional connectivity and PSQI persisted 1 month after the completion of rTMS as evidenced by subsequent electroencephalography (EEG) recordings and the PSQI assessment.ConclusionBased on these results, we established a link between alterations in functional connectivity and clinical outcomes of rTMS, which suggested that EEG-derived functional connectivity changes were associated with clinical improvement of rTMS in treating CID. These findings provide preliminary evidence that rTMS may improve insomnia symptoms by modifying functional connectivity, which can be used to inform prospective clinical trials and potentially for treatment optimization.

Drought stress is one of the major abiotic stresses to wheat worldwide, with negative effects on wheat growth and yield. Assessing genetic variation and drought stress tolerance of key agronomic and physiological traits of spring wheat and screening germplasm resources for higher drought tolerance and yield stability are a prerequisite for developing new, better-adapted spring wheat varieties. This study evaluated nine important agronomic and physiological traits in 152 spring wheat cultivars under non-stress (NS) and drought-stress (DS) conditions. Under DS conditions, grain yield per plot (GYP) and grain weight per spike (GWE) were significantly reduced by 33.8% and 31.7%, and their drought-tolerance indexes (DIs) were only 0.66 and 0.69, respectively, indicating that GYP and GWE are the most susceptible traits to drought stress. The SPAD value of flag leave at flowering stage decreased by 13.9% under DS conditions, and the DI of SPAD was 0.86. In addition, DI-SPAD was significantly positively correlated with DIs of plant height (PH), grain number per spikelet (GPS), grain number per spike (GNS), GWE and GYP, indicating that the drought tolerance and yield of wheat are closely related to chlorophyll retention. Six wheat germplasm accessions were identified for their ability to sustain grain yield and improve drought tolerance simultaneously. These results provide insights into the genetic co-variation between grain yield and drought stress tolerance and provide a theoretical basis for the development of new wheat cultivars with excellent drought tolerance and high yields in the presence and absence of drought.

Abstract Background and objective End-tidal PCO2 (PetCO2) patterns during exercise testing as well as ventilatory equivalents for CO2 have been reported for different pulmonary vascular diseases but seldomly for the significant differences in exercise response depending on the etiology of pulmonary hypertension. We aimed to compare PetCO2 change pattern in IPAH and CTEPH with varying severity during incremental cardiopulmonary exercise testing (CPET). Methods 164 IPAH patients and 135 CTEPH patients referred to Shanghai Pulmonary Hospital between 2012 and 2019 were retrospectively recruited into the study. All patients performed CPET and also underwent right-heart catheterization (RHC). Forty-four healthy subjects also performed CPET and were included as controls. Results PetCO2 was significantly lower in IPAH and CTEPH patients as compared to normal subjects. Moreover, the PetCO2 did not rise, in fact fell from rest to anaerobic threshold (AT), then further decreased until peak in both IPAH and CTEPH. PetCO2 value at rest, unloaded, AT and peak were proportionately reduced as the World Health Organization functional class (WHO-Fc) increased in both IPAH and CTEPH patients. The PETCO2 in IPAH patients had significant differences during all phases of exercise between WHO-Fc I-II and III-IV subgroup. CTEPH also demonstrated significant difference except for PetCO2 at peak. PetCO2 values were significantly higher in IPAH during all phases of exercise as compared to CTEPH patients (all P

Abstract Purpose Aberrant epigenetic changes, like DNA methylation, histone modifications, or ubiquitination, could trigger metabolic disorders in human cancer cells. This study planed to uncover the biological roles of epigenetic SPOP/CHAF1A axis in modulating tumor autophagy during Diffuse large B-cell lymphoma (DLBCL) tumorigenesis. Materials and methods The Immunohistochemistry (IHC) was performed to assess the CHAF1A expressions. The expression data of CHAF1A was derived from The Cancer Genome Atlas (TCGA), GSE32918 and GSE83632 datasets. Bioinformatic assays contain differential analysis, functional enrichment analysis and Kaplan–Meier survival curve analysis. The colony generation assay, Transwell assay and CCK-8 assays were conducted for the in vitro assays. The in vivo ubiquitination assays were used to assess regulations of SPOP on CHAF1A. The Chromatin immunoprecipitation (ChIP) assays were used to uncover epigenetic regulations of CHAF1A on TFEB. The relevant DLBCL cells were subcutaneously injected to SCID beige mice to establish the xenograft models. Results Bioinformatic results revealed that CHAF1A expressed highly in DLBCL that were validated in patients samples. Patients with high CHAF1A suffered from inferior prognosis with shorter survival months relative to those with low CHAF1A. High CHAF1A enhanced DLBCL aggressiveness, including cell proliferation, migration and in vivo growth. Mechanistically, E3 ubiquitin ligase SPOP binds to and induces the degradative ubiquitination of CHAF1A via recognizing a consensus SPOP-binding motif in CHAF1A. SPOP is down-regulated in DLBCL and habours two DLBCL-associated mutations. Deficient SPOP leads to accumulated CHAF1A proteins that promote malignant features of DLBCL. Subsequently, ChIP-qPCR assay revealed that CHAF1A directly binds to TFEB promoters to activate the expressions. High CHAF1A could enhance the transcriptional activity of TFEB and downstream genes. The SPOP/CHAF1A axis modulates TFEB-dependent transactivation to regulate the lysosomal biogenesis and autophagy. The in vivo models suggested that TFEB inhibition is effective to suppress growth of SPOP-deficient DLBCLs. Conclusions CHAF1A is aberrantly elevated in SPOP-deficient DLBCL. The in‐depth mechanism understanding of SPOP/CHAF1A/TFEB axis endows novel targets for DLBCL treatment.

Poking palpebral conjunctiva evoked upper-eyelid retraction during ophthalmic surgery. Iatrogenic eyelid ptosis occurred if eyelid branch of lachrymal nerve was sectioned. Mesencephalic trigeminal nucleus (Vme) neurons were labeled when tracer injected into lachrymal nerve innervating eyelid Mueller's muscle. Masseter afferent Vme neurons projecting to oculomotor nucleus (III) was observed in toad and rat, which helps amphibians to stare prey when they open mouth widely to prey. We hypothesized single Vme neurons may have peripheral collaterals to both eyelid and masseter muscles. WGA-594 was injected into upper eyelid, and WGA-488 was simultaneously delivered into ipsilateral masseter muscle in the same rat. Then, double labeled Vme neurons were found under both conventional and confocal microscope. Meanwhile, contact of WGA-594 positive eyelid afferent Vme neurons with WGA-488 labeled masseter afferent ones were observed sometimes. Combined with our previous observation of oculomotor projection Vme neurons, we thought WGA-594/488 double labeled Vme cells, at least some of them, are oculomotor projecting ones. Contact between eyelid and masseter afferent Vme neurons are supposed to be electrotonically coupled, based on a line of previous studies. If exogenous or genetic factors make these Vme neurons misinterpret masseter input as eyelid afferent signals, these Vme neurons might feedforward massages to eyelid retractor motoneurons in the III. Besides, oculomotor projecting Vme neurons might be co-fired by adjacent masseter afferent Vme neurons through electrotonic coupling once the masseter muscle is activated. In these cases, Marcus Gunn Syndrome might occur. This finding leads to a new hypothesis for the Syndrome.

Genetic and epigenetic reprogramming caused by disease states in other tissues is always systemically reflected in peripheral blood leukocytes (PBLs). Accurate transcriptional readouts of Messenger RNA (mRNA) and Long non-coding RNA (lncRNA) in peripheral blood leukocytes are fundamental for disease-related study, diagnosis and treatment. However, little is known about the impact of preanalytical variables on RNA quality and downstream messenger RNA and Long non-coding RNA readouts. In this study, we explored the impact of RNA extraction kits and timing of blood placement on peripheral blood leukocyte-derived RNA quality. A novel enhanced evaluation system including RNA yields, purity, RNA integrity number (RIN) values and β-actin copies was employed to more sensitively identify RNA quality differences. The expression levels of informative mRNAs and Long non-coding RNAs in patients with chronic obstructive pulmonary disease (COPD) or triple-negative breast cancer (TNBC) were measured by Quantitative reverse transcription polymerase chain reaction (qRT–PCR) to investigate the impact of RNA quality on transcriptional readouts. Our results showed that the quality of RNA extracted by different kits varies greatly, and commercial kits should be evaluated and managed before batch RNA extraction. In addition, the quality of extracted RNA was highly correlated with the timing of blood placement, and the copy number of β-actin was significantly decreased after leaving blood at RT over 12 h. More importantly, compromised RNA leads to skewed transcriptional readouts of informative mRNAs and Long non-coding RNAs in patients with chronic obstructive pulmonary disease or triple-negative breast cancer. These findings have significant implications for peripheral blood leukocyte-derived RNA quality management and suggest that quality control is necessary prior to the analysis of patient messenger RNA and Long non-coding RNA expression.

Abstract Background C-C motif chemokine ligand 2 (CCL2) is reported to be involved in the pathogenesis of various neurological and/or psychiatric diseases. Tissue or cellular expression of CCL2, in normal or pathological condition, may play an essential role in recruiting monocytes or macrophages into targeted organs, and be involved in a certain pathogenic mechanism. However, few studies focused on tissue and cellular distribution of the CCL2 peptide in brain grey and white matters (GM, WM), and the changes of the GM and WM cellular CCL2 level in septic or endotoxic encephalopathy was not explored. Hence, the CCL2 cellular distribution in the front brain cortex and the corpus callosum (CC) was investigated in the present work by using immunofluorescent staining. Results (1) CCL2 like immunoreactivity (CCL2-ir) in the CC is evidently higher than the cortex. When the measurement includes ependymal layer attached to the CC, CCL2-ir intensity is significantly higher than cortex. (2) Structures in perivascular areas, most of them are GFAP positive, contribute major CCL2-ir positive profiles in both GM and WM, but apparently more in the CC, where they are bilaterally distributed in the lateral CC between the cingulate cortex and ventricles. (3) The neuron-like CCL2-ir positive cells in cortex are significantly more than in the CC, and that number is significantly increased in the cortex following systemic lipopolysaccharide (LPS), but not in the CC. (4) In addition to CCL2-ir positive perivascular rings, more CCL2-ir filled cashew shape elements are observed, probably inside of microvasculature, especially in the CC following systemic LPS. (5) Few macrophage/microglia marker-Iba-1 and CCL2-ir co-labeled structures especially the soma is found in normal cortex and CC; the co-localizations are significantly augmented following systemic LPS, and co-labeled amoeba like somata are presented. (6) CCL2-ir and astrocyte marker GFAP or Iba-1 double labeled structures are also observed within the ependymal layer. No accumulation of neutrophils was detected. Conclusion There exist differences in the cellular distribution of the CCL2 peptide in frontal cortex GM and subcortical WM–CC, in both the physiological condition and experimental endotoxemia. Which might cause different pathological change in the GM and WM.

The Ice, Cloud, and Land Elevation Satellite-2 (ICESat-2) is equipped with the Advanced Topographic Laser Altimeter System (ATLAS), which can achieve high-precision ground detection. However, due to its low pulse energy and high sensitivity, it is also affected by noise when obtaining data. Therefore, data denoising is critical to the subsequent processing and application. In this study, a multilevel filtering algorithm is proposed to denoise the daytime photon cloud data with high background noise. Firstly, the Random Sample Consensus (RANSAC) algorithm is used to roughly denoise the daytime photon cloud data with high background noise, and a signal point cloud buffer is established to remove most of the noise points. Subsequently, the horizontal continuity parameter is calculated based on the photon cloud data following the rough denoising process. Based on this parameter, the shape and size of the search domain of the results of the subsequent fine denoising algorithm are adaptively improved. Finally, three filtering directions (a horizontal direction, an intra-group unified direction, and an adaptive direction for each photon) are proposed, and a hybrid algorithm combining the Ordering Points to Identify the Clustering Structure (OPTICS) density clustering algorithm and the Relative Neighboring Relationship K-nearest neighbors-based noise removal (RNR−KNNB) algorithm is employed to accurately denoise the photon cloud data in the three filtering directions. Furthermore, the RANSAC algorithm based on a sliding overlap window is used to remove outliers for the weak beam fine denoising photon cloud data. The results indicate that, for the strong beams, the denoising accuracy of the multilevel filtering algorithm in the three filtering directions is comparable (Rs ≥ 0.96, F ≥ 0.67), and they are all better than that of the ATL08 algorithm (Rs/Rn/p/F = 0.85/0.67/0.52/0.65). For weak beams, the denoising accuracy of the multilevel filtering algorithm in the horizontal direction and the intra-group unified direction is similar (Rs = 0.92, F = 0.69), and it is superior to the denoising results in the adaptive direction of each photon and the ATL08 algorithm (Rs/Rn/p/F = 0.94/0.84/0.51/0.65, 0.88/0.87/0.55/0.67, respectively). For strong and weak beams, the p-value and F-value of the denoising results of multilevel filtering algorithms in three different filtering directions increase with the increase of SNR value. It is demonstrated that SNR is an important factor affecting the denoising results of algorithms. The multilevel filtering algorithm proposed in the study can effectively achieve precise denoising of daytime photon cloud data with high background noise, and the three different filtering directions have different effects on the denoising results of strong and weak beam photon cloud data. This can provide technical and methodological guidance for subsequent photon cloud data filtering processing.

Mussel is an economically and ecologically important species widely distributed throughout the world. The mussel adheres to the attachment substrate by secreting byssus external to the body. Various environmental and biological factors influence the process of byssus secretion, and the present study investigated the effect of starvation on byssal secretion in the hard-shelled mussel Mytilus coruscus. Histological changes in mussel foot secretory glands and gene expression of mussel foot proteins were also determined. The experimental setup consisted of starvation treatments for 7, 14 and 21 days, and the control groups. The results showed that the number of produced byssus was higher in the starvation group compared to the control (CTR) group, and the starvation group had a significantly higher of byssal shedding number from 6 days of starvation treatment onwards (p < 0.05). The byssal thread diameter was significantly reduced in all starvation treatment groups (p < 0.05). However, starvation treatment had no effect on the length of the byssal thread (p > 0.05). After 21 days of starvation treatment, the byssal thread volume was significantly lower than that of the CTR group (p < 0.05). A significant decrease in the breaking force of the byssal thread was observed after 14 and 21 days of starvation treatment (p < 0.05), along with an upward shift in the breakpoints. Starvation treatment significantly reduced the percentage of foot secretory glands area to total tissue (p < 0.05). The expression of the mussel foot protein genes (Mcfp-1P and Mcfp-1T) was significantly up-regulated at 7 days of starvation treatment (p < 0.05). These findings reveal that starvation weakens byssal thread performance by influencing mussel foot secretory glands, which increases the dislodgment risks of suspended-cultured mussels.

Abstract Background Primary breast double-hit lymphoma (PB-DHL) is a rare, highly aggressive malignancy that poses challenges regarding accurate diagnosis and selecting optimal treatment regimens. Methods We retrospectively reviewed 48 cases of patients diagnosed with PB-DHL in six academic centres between June 2014 and June 2020 in China. Study-specific data were recorded, including treatment options, therapeutic evaluation, prognostic factors and relapse patterns, and the overall survival (OS) and progression-free survival (PFS) were evaluated. Results In total, 48 patients were enrolled, with 14 patients treated with DA-EPOCH-R/MA (rituximab, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, alternating with high-dose methotrexate and cytarabine), 18 patients treated with DA-EPOCH-R (rituximab, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin), and 16 patients treated with R-HyperCVAD (rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, alternating with cytarabine plus methotrexate). The overall 5-year OS and PFS rates were 41.7% (95% confidence interval [CI], 27.6–56.8%) and 37.5% (95% CI, 24.0–52.6%), respectively. Of the three treatment regimens, the 5-year OS was higher in DA-EPOCH-R/MA group than in the DA-EPOCH-R or R-HyperCVAD subgroups (57.1% vs. 38.9% vs. 31.3%; P = 0.016), as was the 5-year PFS (50.0% vs. 38.9% vs. 25.0%; P = 0.035). Autologous stem cell transplantation (ASCT) prolonged the OS and PFS compared with non-ASCT patients (5-year OS: 72.2% vs. 23.3%; P

Abstract Larval metamorphosis in bivalves is a key event for the larva-to-juvenile transformation. Previously we have identified a thyroid hormone receptor (TR) gene that is crucial for larvae to acquire “competence” for the metamorphic transition in the mussel Mytilus courscus (Mc). The mechanisms of thyroid signaling in bivalves are still largely unknown. In the present study, we molecularly characterized the full-length of two iodothyronine deiodinase genes (McDx and McDy). Phylogenetic analysis revealed that deiodinases of molluscs (McDy, CgDx and CgDy) and vertebrates (D2 and D3) shared a node representing an immediate common ancestor, which resembled vertebrates D1 and might suggest that McDy acquired specialized function from vertebrates D1. Anti-thyroid compounds, methimazole (MMI) and propylthiouracil (PTU), were used to investigate their effects on larval metamorphosis and juvenile development in M. coruscus. Both MMI and PTU significantly reduced larval metamorphosis in response to the metamorphosis inducer epinephrine. MMI led to shell growth retardation in a concentration-dependent manner in juveniles of M. coruscus after 4 weeks of exposure, whereas PTU had no effect on juvenile growth. It is hypothesized that exposure to MMI and PTU reduced the ability of pediveliger larvae for the metamorphic transition to respond to the inducer. The effect of MMI and PTU on larval metamorphosis and development is most likely through a hormonal signal in the mussel M. coruscus, with the implications for exploring the origins and evolution of metamorphosis.

Abstract Background Linear ubiquitination is a novel type of ubiquitination that plays important physiological roles in signalling pathways such as tumour necrosis factor (TNF) signalling. However, little is known about the regulatory mechanisms of linear ubiquitination, except the well-described enzymatic regulators E3 ligase linear ubiquitin chain assembly complex (LUBAC) and deubiquitinase OTULIN. Results Previously, we identified SNX27, a member of the sorting nexin family protein, as a selective linear ubiquitin chain interactor in mass spectrometry-based ubiquitin interaction screening. Here, we demonstrated that the interaction between the linear ubiquitin chain and SNX27 is mediated by the OTULIN. Furthermore, we found that SNX27 inhibits LUBAC-mediated linear ubiquitin chain formation and TNFα-induced signalling activation. Mechanistic studies showed that, upon TNFα stimulation, OTULIN-SNX27 is localised to membrane-associated TNF receptor complex, where OTULIN deubiquitinates the linear polyubiquitin chain that formed by the LUBAC complex. Significantly, chemical inhibition of SNX27-retromer translocation by cholera toxin inhibits OTULIN membrane localization. Conclusions In conclusion, our study demonstrated that SNX27 inhibits TNFα induced NF-κB signalling activation via facilitating OTULIN to localize to TNF receptor complex.

BackgroundReports of the clinical outcomes associated with the co-occurrence of atrial cardiomyopathy (ACM) and lung cancer (LC) are limited.ObjectivesThis study aims to investigate the influence of ACM on the prognosis of LC patients and related clinical determinants.MethodsNewly diagnosed LC patients from January 1st, 2015, to December 31st, 2020, were retrospectively enrolled at the First Affiliated Hospital of Xi’an Jiaotong University. The demographics and overall survival (OS) of the patients with or without ACM were compared. The survival rate was analyzed using the Kaplan–Meier method and multivariate Cox regression analysis. Binary logistic regression analysis was used to determine the risk factors for ACM.ResultsA total of 306 patients (65.04 ± 10.30 years of age, 72.88% male) were analyzed. The prevalence of ACM in the non-small cell lung cancer (241, 78.76%) and small cell lung cancer (65, 21.24%) population was not statistically different. Overall, 53 (17.32%) LC patients had coexisting ACM. ACM patients were older (69 vs. 64, p = 0.0013) and had higher D-dimer levels (1.0 vs. 0.6, p = 0.001), lower serum calcium levels (2.23 vs. 2.31, p = 0.001), lower left ventricular ejection fraction (LVEF) values (67% vs. 69%, p = 0.036) and had more frequent coronary comorbidity disease (16.98% vs. 8.82%, p = 0.031). The median OS for patients with or without ACM was 15 months and 25 months, respectively (p = 0.018). Coexisting ACM compared to non-ACM was associated with worse OS in patients with LC (HR = 1.543, 95% CI: 1.042–2.283, p = 0.030).ConclusionCoexisting ACM is associated with undesirable survival outcomes in patients with LC. These findings could help us to better understand the cardiac burden in these patients and provide additional risk stratification for them.

The metamorphosis process is a critical life-changing event for marine invertebrate planktonic larvae to transform into benthic adults, which is crucial for the shellfish bed’s ecosystem stability and seed production in aquaculture. The mechanism of neuroendocrine regulation in the larval metamorphosis of bivalves remains ambiguous. In the present study, the expression of two deiodinase genes, McDx and McDy, was analyzed by whole-mount in situ hybridization at four larval stages in the hard-shelled mussel Mytilus coruscus. The McDx and McDy localized in visceral tissues, nervous system, mantle, and velum, indicating that two deiodinase genes are essential for larval development in M. coruscus. Knockdown of the McDx and McDy in the pediveliger larvae of M. coruscus using electroporation of siRNA significantly (p < 0.001) reduced McDx and McDy expression. McDx and McDy knockdown reduced larval metamorphosis in 45% and 49% of the pediveliger larvae induced by epinephrine (EPI). It is hypothesised that the knockdown effects of McDx and McDy repress metamorphic induction rather than larval viability, which does not elicit a lethal effect. The present study corroborates a synergistic action of the adrenergic and thyroid hormones signalling pathway in M. coruscus, and suggests the role of McDx and McDy in larval development and metamorphic transition.

Shape segmentation in urban environments forms the foundation for tasks such as classification and reconstruction. Most artificial buildings with complex structures are composed of multiple simple geometric primitives. Based on this assumption, this paper proposes a divisive hierarchical clustering algorithm that uses shape classification and outliers reassignment to segment LiDAR point clouds in order to effectively identify the various shapes of structures that make up buildings. The proposed method adopts a coarse-to-fine strategy. Firstly, based on the geometric properties of different primitives in a Gaussian sphere space, coarse extraction is performed using Gaussian mapping and the DBSCAN algorithm to identify the primary structure of various shapes. Then, the error functions are constructed after parameterizing the recognized shapes. Finally, a minimum energy loss function is built by combining the error functions and binary integer programming (BIP) to redistribute the outlier points. Thereby, the accurate extraction of geometric primitives is achieved. Experimental evaluations on real point cloud datasets show that the indicators of precision, accuracy, and F1 score of our method are 0.98, 0.95, and 0.96 (point assignment) and 0.97, 0.95, and 0.95 (shape recognition), respectively. Compared with other state-of-the-art methods, the proposed method can efficiently segment planar and non-planar structures with higher quality from building point clouds.

Abstract Background Soybean cyst nematode, Heterodera glycines, is one of the most devastating pathogens of soybean and causes severe annual yield losses worldwide. Different soybean varieties exhibit different responses to H. glycines infection at various levels, such as the genomic, transcriptional, proteomic and metabolomic levels. However, there have not yet been any reports of the differential responses of incompatible and compatible soybean varieties infected with H. glycines based on combined metabolomic and transcriptomic analyses. Results In this study, the incompatible soybean variety PI437654 and three compatible soybean varieties, Williams 82, Zhonghuang 13 and Hefeng 47, were used to clarify the differences in metabolites and transcriptomics before and after the infection with HG1.2.3.5.7. A local metabolite-calibrated database was used to identify potentially differential metabolites, and the differences in metabolites and metabolic pathways were compared between the incompatible and compatible soybean varieties after inoculation with HG1.2.3.5.7. In total, 37 differential metabolites and 20 KEGG metabolic pathways were identified, which were divided into three categories: metabolites/pathways overlapped in the incompatible and compatible soybeans, and metabolites/pathways specific to either the incompatible or compatible soybean varieties. Twelve differential metabolites were found to be involved in predicted KEGG metabolite pathways. Moreover, 14 specific differential metabolites (such as significantly up-regulated nicotine and down-regulated D-aspartic acid) and their associated KEGG pathways (such as the tropane, piperidine and pyridine alkaloid biosynthesis, alanine, aspartate and glutamate metabolism, sphingolipid metabolism and arginine biosynthesis) were significantly altered and abundantly enriched in the incompatible soybean variety PI437654, and likely played pivotal roles in defending against HG1.2.3.5.7 infection. Three key metabolites (N-acetyltranexamic acid, nicotine and D,L-tryptophan) found to be significantly up-regulated in the incompatible soybean variety PI437654 infected by HG1.2.3.5.7 were classified into two types and used for combined analyses with the transcriptomic expression profiling. Associated genes were predicted, along with the likely corresponding biological processes, cellular components, molecular functions and pathways. Conclusions Our results not only identified potential novel metabolites and associated genes involved in the incompatible response of PI437654 to soybean cyst nematode HG1.2.3.5.7, but also provided new insights into the interactions between soybeans and soybean cyst nematodes.

Image segmentation is an important task in image processing and analysis but due to the same ground object having different spectra and different ground objects having similar spectra, segmentation, particularly on high-resolution remote sensing images, can be significantly challenging. Since the spectral distribution of high-resolution remote sensing images can have complex characteristics (e.g., asymmetric or heavy-tailed), an innovative image segmentation algorithm is proposed based on the hierarchical Student’s-t mixture model (HSMM) and spatial constraints with adaptive smoothing. Considering the complex distribution of spectral intensities, the proposed algorithm constructs the HSMM to accurately build the statistical model of the image, making more reasonable use of the spectral information and improving segmentation accuracy. The component weight is defined by the attribute probability of neighborhood pixels to overcome the influence of image noise and make a simple and easy-to-implement structure. To avoid the effects of artificially setting the smoothing coefficient, the gradient optimization method is used to solve the model parameters, and the smoothing coefficient is optimized through iterations. The experimental results suggest that the proposed HSMM can accurately model asymmetric, heavy-tailed, and bimodal distributions. Compared with traditional segmentation algorithms, the proposed algorithm can effectively overcome noise and generate more accurate segmentation results for high-resolution remote sensing images.

Many marine invertebrate larvae undergo complex morphological and physiological changes during the planktonic—benthic transition (a.k.a. metamorphosis). In this study, transcriptome analysis of different developmental stages was used to uncover the molecular mechanisms underpinning larval settlement and metamorphosis of the mussel, Mytilus coruscus. Analysis of highly upregulated differentially expressed genes (DEGs) at the pediveliger stage revealed enrichment of immune-related genes. The results may indicate that larvae co-opt molecules of the immune system to sense and respond to external chemical cues and neuroendocrine signaling pathways forecast and trigger the response. The upregulation of adhesive protein genes linked to byssal thread secretion indicates the anchoring capacity required for larval settlement arises prior to metamorphosis. The results of gene expression support a role for the immune and neuroendocrine systems in mussel metamorphosis and provide the basis for future studies to disentangle gene networks and the biology of this important lifecycle transformation.

Abstract Background Family history (FH) information, including family members, side of family of family members (i.e., maternal or paternal), living status of family members, observations (diseases) of family members, etc., is very important in the decision-making process of disorder diagnosis and treatment. However FH information cannot be used directly by computers as it is always embedded in unstructured text in electronic health records (EHRs). In order to extract FH information form clinical text, there is a need of natural language processing (NLP). In the BioCreative/OHNLP2018 challenge, there is a task regarding FH extraction (i.e., task1), including two subtasks: (1) entity identification, identifying family members and their observations (diseases) mentioned in clinical text; (2) family history extraction, extracting side of family of family members, living status of family members, and observations of family members. For this task, we propose a system based on deep joint learning methods to extract FH information. Our system achieves the highest F1- scores of 0.8901 on subtask1 and 0.6359 on subtask2, respectively.

The baseline International Prognostic Index (IPI) is not sufficient for the initial risk stratification of patients with diffuse large B-cell lymphoma (DLBCL) treated with R‐CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone). The aims of this study were to evaluate the prognostic relevance of early risk stratification in DLBCL and develop a new stratification system that combines an interim evaluation and IPI. This multicenter retrospective study enrolled 314 newly diagnosed DLBCL patients with baseline and interim evaluations. All patients were treated with R-CHOP or R-CHOP-like regimens as the first-line therapy. Survival differences were evaluated for different risk stratification systems including the IPI, interim evaluation, and the combined system. When stratified by IPI, the high-intermediate and high-risk groups presented overlapping survival curves with no significant differences, and the high-risk group still had >50% of 3-year overall survival (OS). The interim evaluation can also stratify patients into three groups, as 3-year OS and progression-free survival (PFS) rates in patients with stable disease (SD) and progressive disease (PD) were not significantly different. The SD and PD patients had significantly lower 3-year OS and PFS rates than complete remission and partial response patients, but the percentage of these patients was only ~10%. The IPI and interim evaluation combined risk stratification system separated the patients into low-, intermediate-, high-, and very high-risk groups. The 3-year OS rates were 96.4%, 86.7%, 46.4%, and 40%, while the 3-year PFS rates were 87.1%, 71.5%, 42.5%, and 7.2%. The OS comparison between the high-risk group and very high-risk group was marginally significant, and OS and PFS comparisons between any other two groups were significantly different. This combined risk stratification system could be a useful tool for the prognostic prediction of DLBCL patients.

Backgrounds: Nowadays, risks of Cognitive Impairment (CI) [highly suspected Alzheimer's disease (AD) in this study] threaten the quality of life for more older adults as the population ages. The emergence of Transcranial Magnetic Stimulation-Electroencephalogram (TMS-EEG) enables noninvasive neurophysiological investi-gation of the human cortex, which might be potentially used for CI detection.Objectives: The aim of this study is to explore whether the spatiotemporal features of TMS Evoked Potentials (TEPs) could classify CI from healthy controls (HC).Methods: Twenty-one patients with CI and 22 HC underwent a single-pulse TMS-EEG stimulus in which the pulses were delivered to the left dorsolateral prefrontal cortex (left DLPFC). After preprocessing, seven regions of interest (ROIs) and two most reliable TEPs' components: N100 and P200 were selected. Next, seven simple and interpretable linear features of TEPs were extracted for each region, three common machine learning algorithms including Support Vector Machine (SVM), Random Forest (RF), and K-Nearest Neighbor (KNN) were used to detect CI. Meanwhile, data augmentation and voting strategy were used for a more robust model. Finally, the performance differences of features in classifiers and their contributions were investigated.Results: 1. In the time domain, the features of N100 had the best performance in the SVM classifier, with an accuracy of 88.37%. 2. In the aspect of spatiality, the features of the right frontal region and left parietal region had the best performance in the SVM classifier, with an accuracy of 83.72%. 3. The Local Mean Field Power (LMFP), Average Value (AVG), Latency and Amplitude contributed most in classification.Conclusions: The TEPs induced by TMS over the left DLPFC has significant differences spatially and temporally between CI and HC. Machine learning based on the spatiotemporal features of TEPs have the ability to separate the CI and HC which suggest that TEPs has potential as non-invasive biomarkers for CI diagnosis.

ObjectiveCognitive impairment occurs frequently in Parkinson’s disease (PD) and negatively impacts the patient’s quality of life. However, its pathophysiological mechanism remains unclear, hindering the development of new therapies. Changes in brain connectivity are related to cognitive impairment in patients with PD, with the dorsolateral prefrontal cortex (DLPFC) being considered the essential region related to PD cognitive impairment. Nevertheless, few studies have focused on the global connectivity responsible for communication with the DLPFC node, the posterior division of the middle frontal gyrus (PMFG) in patients with PD; this was the focus of this study.MethodsWe applied resting-state electroencephalography (EEG) and calculated a reliable functional connectivity measurement, the debiased weighted phase lag index (dWPLI), to examine inter-regional functional connectivity in 68 patients with PD who were classified into two groups according to their cognitive condition.ResultsWe observed that altered left and right PMFG-based functional connectivity associated with cognitive impairment in patients with PD in the theta frequency bands under the eyes closed condition (r = −0.426, p < 0.001 and r = −0.437, p < 0.001, respectively). Exploratory results based on the MoCA subdomains indicated that poorer visuospatial function was associated with higher right PMFG-based functional connectivity (r = −0.335, p = 0.005), and poorer attention function was associated with higher left and right PMFG-based functional connectivity (r = −0.380, p = 0.001 and r = −0.256, p = 0.035, respectively). Further analysis using logistic regression and receiver operating characteristic (ROC) curves found that this abnormal functional connectivity was an independent risk factor for cognitive impairment [odds ratio (OR): 2.949, 95% confidence interval (CI): 1.294–6.725, p = 0.01 for left PMFG; OR: 11.278, 95% CI: 2.578–49.335, p = 0.001 for right PMFG, per 0.1 U], and provided moderate classification power to discriminate between cognitive abilities in patients with PD [area under the ROC curve (AUC) = 0.770 for left PMFG; AUC = 0.809 for right PMFG].ConclusionThese preliminary findings indicate that abnormal PMFG-based functional connectivity patterns associated with cognitive impairment in the theta frequency bands under the eyes closed condition and altered functional connectivity patterns have the potential to act as reliable biomarkers for identifying cognitive impairment in patients with PD.

Background: Increasing evidence demonstrates that repetitive transcranial magnetic stimulation (rTMS) treatment of the dorsolateral prefrontal cortex is beneficial for improving cognitive function in patients with Alzheimer’s disease (AD); however, the underlying mechanism of its therapeutic effect remains unclear.Objectives/Hypothesis: The aim of this study was to investigate the impact of rTMS to the dorsolateral prefrontal cortex on functional connectivity along with treatment response in AD patients with different severity of cognitive impairment.Methods: We conducted a 2-week treatment course of 10-Hz rTMS over the left dorsolateral prefrontal cortex in 23 patients with AD who were split into the mild or moderate cognitive impairment subgroup. Resting state electroencephalography and general cognition was assessed before and after rTMS. Power envelope connectivity was used to calculate functional connectivity at the source level. The functional connectivity of AD patients and 11 cognitively normal individuals was compared.Results: Power envelope connectivity was higher in the delta and theta bands but lower in the beta band in the moderate cognitive impairment group, compared to the cognitively normal controls, at baseline (p < 0.05). The mild cognitive impairment group had no significant abnormities. Montreal Cognitive Assessment scores improved after rTMS in the moderate and mild cognitive impairment groups. Power envelope connectivity in the beta band post-rTMS was increased in the moderate group (p < 0.05) but not in the mild group. No significant changes in the delta and theta band were found after rTMS in both the moderate and mild group.Conclusion: High-frequency rTMS to the dorsolateral prefrontal cortex modulates electroencephalographic functional connectivity while improving cognitive function in patients with AD. Increased beta connectivity may have an important mechanistic role in rTMS therapeutic effects.

Volatile organic compounds (VOC) harm human health seriously in the air. Therefore, it is essential to recognize VOC gases qualitatively and quantitatively. The dynamic measurement method can improve the selectivity of metal oxide semiconductor (MOS) gas sensors to VOC, but there is a problem of the insufficient number of characteristic peaks. From the experimental point of view, the primary judgment basis for the correct qualitative and quantitative recognition of VOC gases by the dynamic measurement method is the characteristic peak of the dynamic response signal. However, the traditional dynamic measurement method generally only has two characteristic peaks. In this experiment, the voltage was changed at the time of the second characteristic peak by controlling the constant dynamic response period. Taking ethyl alcohol as an example, the experimental results show that the characteristic peak of the dynamic response signal does not increase when the voltage is constant. However, a new characteristic peak will appear based on a continuously rising heating voltage. The characteristic peaks of the dynamic response of n-propyl alcohol, isopropyl alcohol, and n-butyl alcohol were also increased based on the rising heating voltage waveform. Based on the K-Nearest-Neighbors algorithm, the qualitative and quantitative recognition rate of the four alcohol homologue gases reached 100%.

Oxidative stress is more likely to cause damage to neuronal cells and mediates some neurodegenerative disorders. It is well known that natural antioxidants can prevent oxidative stress damage and become a potential therapeutic strategy. Noni juice obtained from the fruit of the tree Morinda citrifolia, as a folk medicine, has been used for over two thousand years. In the current study, the neuroprotective effect and mechanism of noni juice extracts against tert-Butyl hydroperoxide (TBHP)-induced SH-SY5Y cell damage were investigated. The results demonstrated that chloroform fraction (CF) and aqueous fraction (AF) of noni juice protected SH-SY5Y cells against TBHP-induced oxidative stress and the associated apoptosis effectively. CF and AF treatment significantly weakened the TBHP-induced cytotoxicity, reactive oxygen species generation, mitochondrial membrane depolarization, and apoptotic features. CF and AF restored cellular antioxidant enzyme activity; upregulated expression of heme oxygenase-1, catalase, and superoxide dismutase-1; and increased the nuclear accumulation of nuclear factor-erythroid 2 related factor 2 (Nrf2). The antioxidant and neuroprotection potential of CF may account for its high total phenolic and flavonoid content, while AF may be rich in polysaccharides. These results suggest that CF and AF exhibit antioxidant defense through the upregulation of Nrf2 along with endogenous antioxidants and reduce apoptosis via inhibiting the mitochondrial pathway to protect SH-SY5Y cells damaged by TBHP. CF and AF might be developed as agents for neurodegeneration prevention or therapy.

Classification of Alzheimer's Disease (AD) has been becoming a hot issue along with the rapidly increasing number of patients. This task remains tremendously challenging due to the limited data and the difficulties in detecting mild cognitive impairment (MCI). Existing methods use gait [or EEG (electroencephalogram)] data only to tackle this task. Although the gait data acquisition procedure is cheap and simple, the methods relying on gait data often fail to detect the slight difference between MCI and AD. The methods that use EEG data can detect the difference more precisely, but collecting EEG data from both HC (health controls) and patients is very time-consuming. More critically, these methods often convert EEG records into the frequency domain and thus inevitably lose the spatial and temporal information, which is essential to capture the connectivity and synchronization among different brain regions. This paper proposes a cascade neural network with two steps to achieve a faster and more accurate AD classification by exploiting gait and EEG data simultaneously. In the first step, we propose attention-based spatial temporal graph convolutional networks to extract the features from the skeleton sequences (i.e., gait) captured by Kinect (a commonly used sensor) to distinguish between HC and patients. In the second step, we propose spatial temporal convolutional networks to fully exploit the spatial and temporal information of EEG data and classify the patients into MCI or AD eventually. We collect gait and EEG data from 35 cognitively health controls, 35 MCI, and 17 AD patients to evaluate our proposed method. Experimental results show that our method significantly outperforms other AD diagnosis methods (91.07 vs. 68.18%) in the three-way AD classification task (HC, MCI, and AD). Moreover, we empirically found that the lower body and right upper limb are more important for the early diagnosis of AD than other body parts. We believe this interesting finding can be helpful for clinical researches.

A 64-year old Chinese male patient was admitted to our hospital because of severe jaundice that persisted for 2 months. No swollen lymph nodes or hepatosplenomegaly was detected on physical examination. His laboratory data indicated high levels of direct bilirubin, alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase. No abnormality was revealed on abdominal computed tomography (CT). However, positron emission tomography (PET)-CT revealed diffuse hypermetabolism in the liver and spleen. Ultimately, liver biopsy guided by PET-CT was performed, revealing that atypical lymphocytes diffusely infiltrated the liver. The immunohistochemical analysis demonstrated that the tumor cells were positive for CD20, Bcl-2, Bcl-6, MUM1, and c-Myc but negative for CD3, CD4, CD8, and CD10. Based on these findings, this patient was diagnosed with primary hepatosplenic diffuse large B-cell lymphoma. After the definite diagnosis, he received chemotherapy and remained in good health as of September 2019.

The heat shock transcription factor (HSF) binds to cis-regulatory motifs known as heat shock elements (HSEs) to mediate the transcriptional response of HSF target genes. However, the HSF–HSEs interaction is not clearly understood. Using the newly released genome reference sequence of bread wheat, we identified 39,478 HSEs (95.6% of which were non-canonical HSEs) and collapsed them into 30,604 wheat genes, accounting for 27.6% wheat genes. Using the intensively heat-responsive transcriptomes of wheat, we demonstrated that canonical HSEs have a higher propensity to induce a response in the closest downstream genes than non-canonical HSEs. However, the response magnitude induced by non-canonical HSEs was comparable to that induced by canonical HSEs. Significantly, some non-canonical HSEs that contain mismatched nucleotides at specific positions within HSEs had a larger response magnitude than that of canonical HSEs. Consistently, most of the HSEs identified in the promoter regions of heat shock proteins were non-canonical HSEs, suggesting an important role for these non-canonical HSEs. Lastly, distinct diverged biological processes were observed between genes containing different HSE types, suggesting that sequence variation in HSEs plays a key role in the evolution of heat responses and adaptation. Our results provide a new perspective to understand the regulatory network underlying heat responses.

Abstract Background Blood–brain barrier (BBB) breakdown and inflammatory responses are the major causes of tissue-type plasminogen activator (tPA)-induced hemorrhagic transformation (HT), while high-mobility group box 1 (HMGB1) exacerbates inflammatory damage to BBB during the process of brain ischemia/reperfusion. This study aimed to investigate the change of HMGB1 after thrombolytic therapy and whether blocking HMGB1 could ameliorate the neurovasculature complications secondary to tPA treatment in stroke rats. Methods Sera from acute stroke patients and rats with thrombolytic therapy were collected to investigate HMGB1 secretion. Male Sprague-Dawley rats with 2 h or 4.5 h middle cerebral artery occlusion were continuously infused with tPA followed by administration of membrane permeable HMGB1-binding heptamer peptide (HBHP). The mortality rate, neurological score, HT, brain swelling, BBB permeability, and inflammatory factors were determined. Results The results revealed that HMGB1 levels were elevated in both stroke patients and rats after tPA treatment. Blocking HMGB1 signaling by HBHP in the rat model of 4.5 h brain ischemia significantly attenuated tPA-related complications, including mortality rate, the degree of hemorrhage, brain swelling, neurological deficits, BBB impairment, microglia activation, and the expressions of inflammatory cytokines. Conclusions tPA treatment might induce HMGB1 secretion while blocking HMGB1 with HBHP could markedly reduce the risk of thrombolysis-associated brain hemorrhage and mortality through attenuating BBB damage and inflammatory reactions. These results indicate that HMGB1 may potentiate the risk of HT in tPA administration and that blocking HMGB1 signaling would be helpful in preventing complications brought by thrombolysis in ischemic stroke. Trial registration http://www.chictr.org.cn. Unique identifier: ChiCTR-OOC-16010052. Registered 30 November 2016.

Abstract Background The cuticle covers the surface of the polysaccharide cell wall of leaf epidermal cells and forms an essential diffusion barrier between the plant and the environment. The cuticle is composed of cutin and wax. Cuticular wax plays an important role in the survival of plants by serving as the interface between plants and their biotic and abiotic environments, especially restricting nonstomatal water loss. Leaf cuticular waxes of hexaploid wheat at the seedling stage mainly consist of primary alcohols, aldehydes, fatty acids, alkane and esters. Primary alcohols account for more than 80% of the total wax load. Therefore, we cloned several genes encoding fatty acyl-coenzyme A reductases from wheat and analyzed their function in yeast and plants. We propose the potential use of these genes in wheat genetic breeding. Results We reported the cloning and characterization of three TaFARs, namely TaFAR6, TaFAR7 and TaFAR8, encoding fatty acyl-coenzyme A reductases (FAR) in wheat leaf cuticle. Expression analysis revealed that TaFAR6, TaFAR7 and TaFAR8 were expressed at the higher levels in the seedling leaf blades, and were expressed moderately or weakly in stamen, glumes, peduncle, flag leaf blade, sheath, spike, and pistil. The heterologous expression of three TaFARs in yeast (Saccharomyces cerevisiae) led to the production of C24:0 and C26:0 primary alcohols. Transgenic expression of the three TaFARs in tomato (Solanum lycopersicum) and rice (Oryza sativa) led to increased accumulation of C24:0–C30:0 primary alcohols. Transient expression of GFP protein-tagged TaFARs revealed that the three TaFAR proteins were localized to the endoplasmic reticulum (ER), the site of wax biosynthesis. The three TaFAR genes were transcriptionally induced by drought, cold, heat, powdery mildew (Blumeria graminis) infection, abscisic acid (ABA) and methyl jasmonate (MeJa) treatments. Conclusions These results indicated that wheat TaFAR6, TaFAR7 and TaFAR8 are involved in biosynthesis of very-long-chain primary alcohols in hexaploid wheat and in response to multiple environmental stresses.

Oxidation reactions play a critical role in processes involving energy utilization, chemical conversion, and pollutant elimination. However, due to its spin-forbidden nature, the reaction of molecular dioxygen (O2) with a substrate is difficult under mild conditions. Herein, we describe a system that activates O2 via the direct modulation of its spin state by mechanical energy-induced triboelectric corona plasma, enabling the CO oxidation reaction under normal temperature and pressure. Under optimized reaction conditions, the activity was 7.2 μmol h−1, and the energy consumption per mole CO was 4.2 MJ. The results of kinetic isotope effect, colorimetry, and density functional theory calculation studies demonstrated that electrons generated in the triboelectric plasma were directly injected into the antibonding orbital of O2 to form highly reactive negative ions O2−, which effectively promoted the rate-limiting step of O2 dissociation. The barrier of the reaction of O2− ions and CO molecular was 3.4 eV lower than that of O2 and CO molecular. This work provides an effective strategy for using renewable and green mechanical energy to realize spin-forbidden reactions of small molecules.

Awns play important roles in seed dispersal, protection against predators, and photosynthesis. The characterization of genes related to the formation of awns helps understand the regulation mechanisms of awn development. In the present study, the “double-awn” wheat 4045, which features super-long lemma awns and long glume awns, and an awnless wheat line, Zhiluowumai, were used to investigate QTLs or genes involved in awn development. QTL analysis identified three loci—Qawn-1D, Qawn-5A, and Qawn-7B—using a population of 101 4045 × ZLWM F2 plants. Fine mapping with a total of 9018 progenies narrowed the mapping interval of Qawn-5A to an 809-kb region, which was consistent with the B1 locus, containing five genes on chromosome 5AL. Gene structure and expression analysis indicated that TraesCS5A02G542800 was the causal gene, which was subsequently verified by overexpression of TraesCS5A02G542800 in a “double-awn” wheat, Yangmai20. The retained “double-awn” phenotype of transgenic plants suggested that B1 represses the elongation but does not influence the emergence of the awns. Moreover, 4045 harbors a new allele of B1 with a 261-bp insertion in the promoter region and a lack of the EAR2 motif in the encoding region, which influences several important agronomic traits. In this study, we identify two novel QTLs and a novel allele of B1, providing new resources for exploration of awn development.

Abstract Wheat (Triticum aestivum), one of the world’s most important crops, is facing unprecedented challenges due to global warming. To evaluate the gene resources for heat adaptation in hexaploid wheat, small heat shock proteins (sHSPs), the key plant heat protection genes, were comprehensively analysed in wheat and related species. We found that the sHSPs of hexaploid wheat were massively expanded in A and B subgenomes with intrachromosomal duplications during polyploidization. These expanded sHSPs were under similar purifying selection and kept the expressional patterns with the original copies. Generally, a strong purifying selection acted on the α-crystallin domain (ACD) and theoretically constrain conserved function. Meanwhile, weaker purifying selection and strong positive selection acted on the N-terminal region, which conferred sHSP flexibility, allowing adjustments to a wider range of substrates in response to genomic and environmental changes. Notably, in CI, CV, ER, MI and MII subfamilies, gene duplications, expression variations and functional divergence occurred before wheat polyploidization. Our results indicate the massive expansion of active sHSPs in hexaploid wheat may also provide more raw materials for evolving functional novelties and generating genetic diversity to face future global climate changes, and highlight the expansion of stress response genes with wheat polyploidization.

The Gaussian mixture model (GMM) plays an important role in image segmentation, but the difficulty of GMM for modeling asymmetric, heavy-tailed, or multimodal distributions of pixel intensities significantly limits its application. One effective way to improve the segmentation accuracy is to accurately model the statistical distributions of pixel intensities. In this study, an innovative high-resolution remote sensing image segmentation algorithm is proposed based on a flexible hierarchical GMM (HGMM). The components are first defined by the weighted sums of elements, in order to accurately model the complicated distributions of pixel intensities in object regions. The elements of components are defined by Gaussian distributions to model the distributions of pixel intensities in local regions of the object region. Following the Bayesian theorem, the segmentation model is then built by combining the HGMM and the prior distributions of parameters. Finally, a novel birth or death Markov chain Monte Carlo (BDMCMC) is designed to simulate the segmentation model, which can automatically determine the number of elements and flexibly model complex distributions of pixel intensities. Experiments were implemented on simulated and real high-resolution remote sensing images. The results show that the proposed algorithm is able to flexibly model the complicated distributions and accurately segment images.

Plants, as sessile organisms, evolved a complex and functionally diverse heat shock factor (HSF) gene family to cope with various environmental stresses. However, the limited evolution studies of the HSF gene family have hindered our understanding of environmental adaptations in plants. In this study, a comprehensive evolution analysis on the HSF gene family was performed in 51 representative plant species. Our results demonstrated that the HSFB group which lacks a typical AHA activation domain, was the most ancient, and is under stronger purifying selection pressure in the subsequent evolutionary processes. While, dramatic gene expansion and functional divergence occurred at evolution timescales corresponding to plant land inhabit, which contribute to the emergence and diversification of the HSFA and HSFC groups in land plants. During the plant evolution, the ancestral functions of HSFs were maintained by strong purifying pressure that acted on the DNA binding domain, while the variable oligomerization domain and motif organization of HSFs underwent functional divergence and generated novel subfamilies. At the same time, variations were further accumulated with plant evolution, and this resulted in remarkable functional diversification among higher plant lineages, including distinct HSF numbers and selection pressures of several HSF subfamilies between monocots and eudicots, highlighting the fundamental differences in different plant lineages in response to environmental stresses. Taken together, our study provides novel insights into the evolutionary origin, pattern and selection pressure of plant HSFs and delineates critical clues that aid our understanding of the adaptation processes of plants to terrestrial environments.

The branched spike phenotype is an important supernumerary spikelet trait of Triticum turgidum L. associated with the production of significantly more grains per spike, thereby offering a higher potential yield. However, the genetic basis of branch meristem (BM) development remains to be fully elucidated in wheat. TAW1, an ALOG (Arabidopsis LSH1 and Oryza G1) family gene, has been shown to function as a unique regulator in promoting BM development in rice. In this study, we found that the development pattern of the BMs of the branched spike in wheat was similar to the indeterminate BMs of rice. Moreover, phylogenetic analysis classified the ALOG genes into 12 groups. This family of genes was found to have evolved independently in eudicots and monocots and was evolutionarily conserved between wheat and rice as well as during wheat polyploidization. Furthermore, experiments revealed that TtALOG2-1A, a TAW1-homologous gene, plays a significant role in regulating the transition of indeterminate BM fate. Finally, large-scale RNA-sequencing studies and quantitative real-time polymerase chain reaction (qRT-PCR) experiments revealed that members of the TtALOGs may act upstream of the TtMADS22, TtMADS47, and TtMADS55 genes to promote indeterminate BM activities. Our findings further knowledge on BM development in wheat.

To identify the pulmonary hypertension (PH) patients who develop an exercise induced venous-to-systemic shunt (EIS) by performing the cardiopulmonary exercise test (CPET), analyse the changes of CPET measurements during exercise and compare the exercise physiology and resting pulmonary hemodynamics between shunt-PH and no-shunt-PH patients.Retrospectively, resting pulmonary function test (PFT), right heart catheterization (RHC), and CPET for clinical evaluation of 104 PH patients were studied.Considering all 104 PH patients by three investigators, 37 were early EIS+, 61 were EIS-, 3 were late EIS+, and 3 others were placed in the discordant group. PeakVO2, AT and OUES were all reduced in the shunt-PH patients compared with the no-shunt-PH subjects, whereas VE/VCO2 slope and the lowest VE/VCO2 increased. Besides, the changes and the response characteristics of the key CPET parameters at the beginning of exercise in the shunt group were notably different from those of the no shunt one. At cardiac catheterization, the shunt patients had significantly increased mean pulmonary artery pressure (mPAP), mean right atrial pressure (mRAP) and pulmonary vascular resistance (PVR), reduced cardiac output (CO) and cardiac index (CI) compared with the no shunt ones (P

Objective. The aims of this study were to investigate the effects of synchronized dual pulse gastric electrical stimulation (SGES) on gastric motility in different periods for diabetic rats and try to explore the possible mechanisms of the effects. Methods. Forty-six rats were used in the study. Gastric slow waves were recorded at baseline, 7–14-day diabetes and 56–63-day diabetes before and after stimulation and the age-matched control groups. SGES-60 mins and SGES-7 days (60 mins/day) were performed to test the effects on gastric motility and to evaluate glial marker S100B expression in stomach. Results. (1) Gastric emptying was accelerated in 7–14-day diabetes and delayed in 56–63-day diabetes. (2) The S100B expression in 56–63-day diabetes decreased and the ultrastructure changed. (3) The age-associated loss of EGC was observed in 56–63-day control group. (4) SGES was able to not only accelerate gastric emptying but also normalize gastric slow waves. (5) The S100B expression increased after SGES and the ultrastructure of EGC was partially restored. The effect of SGES-7 days was superior to SGES-60 mins. Conclusions. Delayed gastric emptying due to the growth of age may be related to the EGC inactivation. The effects of the SGES on gastric motility may be associated with EGC activation.