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Background : Cardiogenic shock (CS) is the leading cause of the death in patients with ST elevation myocardial infarction (STEMI). Thyroid dysfunction is related to prognosis of patients with myocardial infarction. Hence, the aim of this study is to explore the relationship between thyroid hormones (free triiodothyronine [FT3] and free thyroxine [FT4]) and CS. Method : A total of 1270 patients with STEMI treated with percutaneous coronary intervention (PCI) were consecutively enrolled in our study. Patients were classified into two groups according to with or without CS during hospitalization. Stepwise multivariate logistic analysis was conducted to investigate the association of thyroid hormones and CS. Restricted cubic spline method was employed to further explore relationship between CS and thyroid hormones. Results : Patients who developed CS (n=103) had lower FT3 and higher FT4 on admission. The stepwise logistic analysis showed both FT3 (P=0.038) and FT4 (P=0.024) were independently related to CS. Restricted cubic splines indicated that lower FT3 ( 1.25 ng/dl) was correlated with higher prevalence of CS. Over 2.5 years’ follow-up, patients (n=294) with low FT3 ( =0.88 ng/dl) had the highest all-cause mortality (18.2%), whereas patients (n=293) with high FT3 and low FT4 had the lowest all-cause mortality (3.8%) (P for trend Conclusions : Both FT3 and FT4 are independently associated with in-hospital CS development in patients with STEMI treated with PCI. Patients with lower range of FT3 and upper range of FT4 had the worst outcomes in a long-term follow-up.

N-Dealkylation of amines by metal oxo intermediates (M Created by potrace 1.16, written by Peter Selinger 2001-2019 O) is related to drug detoxification and DNA repair in biological systems. In this study, we report the first example of N-dealkylation of various alkylamines by a luminescent osmium(vi) nitrido complex induced by visible light., The visible light-induced N-dealkylation of various alkylamines by a luminescent osmium(vi) nitrido complex has been investigated. We provide definitive evidence that these reactions occur via an ET/PT mechanism.

Objective One barrier hindering high frequency brain signals (HFBS, >80 Hz) from wide clinical applications is that the brain generates both pathological and physiological HFBS. This study was to find specific biomarkers for localizing epileptogenic zones (EZs). Methods Twenty three children with drug-resistant epilepsy and age/sex matched healthy controls were studied with magnetoencephalography (MEG). High frequency oscillations (HFOs, > 4 oscillatory waveforms) and high frequency spikes (HFSs, > 1 spiky or sharp waveforms) in 80–250 Hz and 250–600 Hz bands were blindly detected with an artificial intelligence method and validated with visual inspection. The magnitude of HFOs and HFSs were quantified with spectral analyses. Sources of HFSs and HFOs were localized and compared with clinical EZs determined by invasive recordings and surgical outcomes. Results HFOs in 80–250 Hz and 250–600 Hz were identified in both epilepsy patients (18/23, 12/23, respectively) and healthy controls (6/23, 4/23, respectively). HFSs in 80–250 Hz and 250–600 Hz were detected in patients (16/23, 11/23, respectively) but not in healthy controls. A combination of HFOs and HFSs localized EZs for 22 (22/23, 96%) patients. Conclusions The results indicate, for the first time, that HFSs are a newer and more specific biomarker than HFOs for localizing EZs because HFOs appeared in both epilepsy patients and healthy controls while HFSs appeared only in epilepsy patients.

Objective: To investigate the influence of liver function damage in patients with hepatocellular carcinoma (HCC) after microwave ablation (MWA) on the prognosis and to establish an algorithm to predict liver function damage.Methods: This is a retrospective study. A total of 745 patients were enrolled and classified into the modeling group and the validation group. The risk factors of liver function damage were analyzed by using logistic regression model. The β coefficients derived from a logistic analysis were used to calculate the risk score. Diagnostic accuracy based on risk score was assessed by the area under the curve (AUC).Results: 69 patients in the modeling group suffered from liver function damage. The 1-,3-,5- and 7-year progression free survival were 69.4%, 37.2%, 22.6% and 12.4% for patients without liver function damage and 69.5%, 33.0%, 14.4% and 0% for patients with liver function damage, respectively (P = 0.537). The 1-, 3-, 5- and 7-year overall survival were 94.3%, 75.9%, 61.5% and 54.5% for patients without liver function damage and 81.3%, 57.1%, 42.7% and 42.7% for those with liver function damage (P = 0.004), respectively. The AUC of the risk score for predicting liver function damage was 0.798 for the modeling group and 0.832 for the validation group. The sensitivity and specificity of the risk score to identify liver function damage was 65.2%, 84.4% in the modeling group and 60.6%, 88.3% in the validation group, respectively.Conclusion: Liver function damage after MWA is unfavorable the long-term prognosis. The prediction algorithm based on five risk factors is robust and can be used to predict possible liver function damage.

TEOSINTE BRANCHED 1/CYCLOIDEA/PROLIFERATING CELL FACTOR 1 (TCP) transcription factors control multiple aspects of growth and development in various plant species. However, few genes were reported to be directly targeted and regulated by them through their specific binding sites, and then uncover their functions in plants. A consensus DNA-binding site motif of TCP2 was identified by random binding site selection (RBSS). DNA recognized by TCP2 contained the motif G(G/T)GGNCC(A/C), which showed high consistency with motifs bound by other TCP domain proteins. Consequently, this motif was regarded as the specific DNA-binding sites of TCP2. Circadian clock associated 1 (CCA1) and EARLY FLOWERING 3 (ELF3) were subsequently considered as potential target genes owing to the containing of the similar TCP2 binding sites or core binding sites GGNCC and found to be positively regulated by TCP2 via DNA binding. Phenotype analysis results showed that mutation and over-expression of TCP2 resulted in variations in leaf morphogenesis, especially the double or triple mutations of TCP2, 4 and 10. Mutations in TCPs caused late flowering. Finally, TCP2 was shown to influence hypocotyl elongation by mediating the jasmonate signaling pathway. Overall, these results provide a basis for future studies aimed at distinguishing the target genes of TCP2 and elucidating the important roles of TCP2 in plant growth and development.

Acute respiratory distress syndrome/acute lung injury (ARDS/ALI) is histologically characterized by extensive alveolar barrier disruption and excessive fibroproliferation responses. Protectin DX (PDX) displays anti‐inflammatory and potent inflammation pro‐resolving actions. We sought to investigate whether PDX attenuates LPS (lipopolysaccharide)‐induced lung injury via modulating epithelial cell injury repair, apoptosis and fibroblasts activation. In vivo, PDX was administered intraperitoneally (IP) with 200 ng/per mouse after intratracheal injection of LPS, which remarkedly stimulated proliferation of type II alveolar epithelial cells (AT II cells), reduced the apoptosis of AT II cells, which attenuated lung injury induced by LPS. Moreover, primary type II alveolar cells were isolated and cultured to assess the effects of PDX on wound repair, apoptosis, proliferation and transdifferentiation in vitro. We also investigated the effects of PDX on primary rat lung fibroblast proliferation and myofibroblast differentiation. Our result suggests PDX promotes primary AT II cells wound closure by inducing the proliferation of AT II cells and reducing the apoptosis of AT II cells induced by LPS, and promotes AT II cells transdifferentiation. Furthermore, PDX inhibits transforming growth factor‐β1 (TGF‐β1) induced fibroproliferation, fibroblast collagen production and myofibroblast transformation. Furthermore, the effects of PDX on epithelial wound healing and proliferation, fibroblast proliferation and activation partly via the ALX/ PI3K signalling pathway. These data present identify a new mechanism of PDX which targets the airway epithelial cell and fibroproliferation are potential for treatment of ARDS/ALI.

Epilepsy is a neurological disease, and the location of a lesion before neurosurgery or invasive intracranial electroencephalography (iEEG) surgery using intracranial electrodes is often very challenging. The high-frequency oscillation (HFOs) mode in MEG signal can now be used to detect lesions. Due to the time-consuming and error-prone operation of HFOs detection, an automatic HFOs detector with high accuracy is very necessary in modern medicine. Therefore, an optimized capsule neural network was used, and a MEG (magnetoencephalograph) HFOs detector based on MEGNet was proposed to facilitate the clinical detection of HFOs. To the best of our knowledge, this is the first time that a neural network has been used to detect HFOs in MEG. After optimized configuration, the accuracy, precision, recall, and F1-score of the proposed detector reached 94%, 95%, 94%, and 94%, which were better than other classical machine learning models. In addition, we used the k-fold cross-validation scheme to test the performance consistency of the model. The distribution of various performance indicators shows that our model is robust.

About 1% of the population around the world suffers from epilepsy. The success of epilepsy surgery depends critically on pre-operative localization of epileptogenic zones. High frequency oscillations including ripples (80-250 Hz) and fast ripples (250-500 Hz) are commonly used as biomarkers to localize epileptogenic zones. Recent literature demonstrated that fast ripples indicate epileptogenic zones better than ripples. Thus, it is crucial to accurately detect fast ripples from ripples signals of magnetoencephalography for improving outcome of epilepsy surgery. This paper proposes an automatic and accurate ripple and fast ripple detection method that employs virtual sample generation and neural networks with an attention mechanism. We evaluate our proposed detector on patient data with 50 ripples and 50 fast ripples labeled by two experts. The experimental results show that our new detector outperforms multiple traditional machine learning models. In particular, our method can achieve a mean accuracy of 89.3% and an average area under the receiver operating characteristic curve of 0.88 in 50 repeats of random subsampling validation. In addition, we experimentally demonstrate the effectiveness of virtual sample generation, attention mechanism, and architecture of neural network models.

BACKGROUND: As one of the main malignant tumors, breast cancer remains a worldwide public health issue. Here, we aimed to analyze the effects of breast-conserving surgery (BCS) combined with sentinel lymph node biopsy (SLNB) and axillary preservation on the recurrence, metastasis, complications, and cosmetic results of early breast cancer patients (BCPs). METHODS: The clinical data of 143 BCPs admitted to our hospital from January 2017 to January 2019 were collected retrospectively, and all patients were female. Patients (76 cases) undergoing BCS combined with SLNB and axillary preservation treatment were set as the combined group, and 67 cases undergoing traditional modified radical surgery were set as the control group. After the perioperative conditions of patients in the two groups were compared, the patients were followed up for 14 months to record information on the quality of life, recurrence, metastasis, complications, and cosmetic results. RESULTS: The operation time, intraoperative blood loss, and extubation time of the combined group were significantly less than the control group (P0.05); the incidence of postoperative complications was 14.92% in the control group, which was significantly higher than the incidence of 3.94% of the combined group (P

Objectives: This study aimed to systematically evaluate the effects of constraint-induced aphasia therapy (CIAT) for aphasic patients reported by randomized controlled trials. Methods: Relevant randomized controlled trials were retrieved from 11 electronic databases. A methodological quality assessment was conducted in accordance with the Cochrane Handbook, and meta-analyses were performed by using RevMan 5.2. A descriptive analysis was conducted when the included trials were not suitable for a meta-analysis. Results: A total of 12 trials were included. A statistically significant group difference was shown from the meta-analysis in the results measured by the Western Aphasia Battery (random-effects model, MD = 1.23, 95% CI = 0.31 to 2.14, P 0.05) and Aachen Aphasia Test (fixed-effects model, MD = −1.11, 95% CI = −4.49 to 2.27, P > 0.05). The descriptive analysis showed positive results in language performances of naming, repetition, and comprehension. Conclusion: This systematic review indicated that CIAT was efficient for improving language performance with regard to naming, comprehension, repetition, written language, and oral language based on the current evidence. And this review provides some meaningful guides for clinical practice: expand the therapy duration to 2 or 3 h per day, focus on naming, and choose the best assessment tool. It also indicates a need for more rigorous, large-scale, and high-quality trials in the future.

Studies in animal models of epilepsy and pre-surgical patients have unanimously found a strong correlation between high-frequency oscillations (HFOs, > 80 Hz) and the epileptogenic zone, suggesting that HFOs can be a potential biomarker of epileptogenicity and epileptogenesis. This consensus includes the definition and standard detection techniques of HFOs, the localizing value of pathological HFOs for epileptic foci, and different ways to distinguish physiological from epileptic HFOs. The latest clinical applications of HFOs in epilepsy and the related findings are also discussed. HFOs will advance our understanding of the pathophysiology of epilepsy.

In head and neck squamous cell carcinoma, immune checkpoint inhibitors (ICI) lead to improved outcomes. There has been reports of accelerated disease progression, or hyperprogression, after ICI initiation. We present a case of hyperprogression after one dose of nivolumab in maxillary sinus squamous cell carcinoma. The patient had complete vision loss due to disease progression into the orbit, as well as intracranial invasion, lytic metastases, and new widespread distal metastases. Hyperprogression can occur after the first dose of immunotherapy. Absent biomarkers regarding individual risk of hyperprogression, caution should be exercised in using ICI in sinonasal cancers with orbital abutting disease. Laryngoscope, 130:907-910, 2020.

Retinal neovascularization (RNV) is a common pathological feature in many kinds of fundus oculi diseases. Sometimes RNV can even lead to severe vision loss. Oxidative injury is one of the main predisposing factors for RNV occurrence and development. The specific mechanism may be closely related to the special structural tissues of the retina. Retinal astrocytes (RACs) are mesenchymal cells located in the retinal neuroepithelial layer. RACs have an intimate anatomical relationship with microvascular endothelial cells. They have a variety of functions, but little is known about the mechanisms by which RACs regulate the function of endothelial cells. The molecules secreted by RACs, such as exosomes, have recently received a lot of attention and may provide potential clues to address the RAC‐mediated modulation of endothelial cells. In this study, we aimed to preliminarily explore the mechanisms of how RAC exosomes generated under oxidative stress are involved in the regulation of endothelial function. Our results showed that the apoptosis and autophagy levels in RACs were positively correlated with the oxidative stress level, and the exosomes generated from RACs under normal and oxidative stress conditions had different effects on the proliferation and migration of endothelial cells. However, the effect of RACs on endothelial cell function could be markedly reversed by the autophagy inhibitor 3‐methyladenine or the exosome inhibitor GW4869. Therefore, oxidative stress can lead to increased autophagy in RACs and can further promote RACs to regulate endothelial cell function by releasing exosomes., Highlights 1.tBHP‐induced oxidative stress can increase the level of autophagy in retinal (RAC) astrocytes.2.RAC with high‐autophagy level has a completely opposite effect on HUVEC functions when compared with normal RAC.3.RACs under different states have different effects on endothelial cell functions by releasing exosomes

To identify abnormal functional connectivity of the default mode network in cingulate gyrus epilepsy, which may yield new information about the default mode network and suggest a new cingulate gyrus epilepsy biomarker. Fifteen patients with cingulate gyrus epilepsy (mean age = 21 years) and 15 healthy controls (mean age = 24 years) were studied in the resting state using magnetoencephalography. Twelve brain areas of interest in the default mode network were extracted and investigated with multifrequency signals that included alpha (α, 8–13 Hz), beta (β, 14–30 Hz), and gamma (γ, 31–80 Hz) band oscillations. Patients with cingulate gyrus epilepsy had significantly greater connectivity in all three frequency bands (α, β, γ). A frequency‐specific elevation of functional connectivity was found in patients compared to controls. The greater functional connectivity in the γ band was significantly more prominent than that of the α and β bands. Patients with cingulate gyrus epilepsy and controls differed significantly in functional connectivity between the left angular gyrus and left posterior cingulate cortex in the α, β, and γ bands. The results of the node degree analysis were similar to those of the functional connectivity analysis. Our findings reveal for the first time that brain activity in the γ band may play a key role in the default mode network in cingulate gyrus epilepsy. Altered functional connectivity of the left angular gyrus and left posterior cingulate cortex may be a new biomarker for cingulate gyrus epilepsy.

Exposure to silica nanoparticles (SNPs) causes lung fibrosis and threatens human health. However, it is unknown if low-dose radiation (LDR) exposure exacerbates SNP-induced lung dysfunction. Thus, the aim of our study was to determine the combined effect of SNPs and LDR on lung fibrosis and elucidate the potential mechanisms involved. We used SNP-induced A549 cells and mouse models and detected gut microbiota alteration by 16S rDNA amplicon sequencing. Additionally, lung fibrosis-related parameters were also detected using hematoxylin and eosin (H&E) staining, immunofluorescence (IF) staining, qRT-PCR, and western blot analysis. The histopathological and IF staining assays illustrated that co-exposure of mice to SNPs and LDR had a significant deleterious effect on both lung function and lung fibrosis, in comparison to exposure to SNPs or LDR alone. Furthermore, the abundance of Bacteroidetes significantly increased while that of Firmicutes significantly decreased following co-exposure to SNPs and LDR. Mechanistically, the Notch cascade was activated in chronically SNP-exposed mice with lung fibrosis and A549 cells. Additionally, the Notch pathway-associated proteins showed increased expression levels in the lungs following SNP exposure both in vivo and in vitro. Notably, SNP-induced dysbiosis of the gut microbiota promoted lung epithelial damage by triggering the Notch pathway, resulting in SNP-induced lung fibrosis. However, oral administration of probiotics protected the mice from SNP-induced lung injury. Our results strongly indicate that the activation of the gut microbiota-dependent Notch pathway in response to co-exposure to SNPs and LDR results in lung epithelial injury in vivo. Probiotics supplementation is a potential way to protect against SNP- and LDR-induced lung fibrosis.

Background Migraine is a common and disabling primary headache, which is associated with a wide range of psychiatric comorbidities. However, the mechanisms of emotion processing in migraine are not fully understood yet. The present study aimed to investigate the neural network during neutral, positive, and negative emotional stimuli in the migraine patients. Methods A total of 24 migraine patients and 24 age- and sex-matching healthy controls were enrolled in this study. Neuromagnetic brain activity was recorded using a whole-head magnetoencephalography (MEG) system upon exposure to human facial expression stimuli. MEG data were analyzed in multi-frequency ranges from 1 to 100 Hz. Results The migraine patients exhibited a significant enhancement in the effective connectivity from the prefrontal lobe to the temporal cortex during the negative emotional stimuli in the gamma frequency (30–90 Hz). Graph theory analysis revealed that the migraine patients had an increased degree and clustering coefficient of connectivity in the delta frequency range (1–4 Hz) upon exposure to positive emotional stimuli and an increased degree of connectivity in the delta frequency range (1–4 Hz) upon exposure to negative emotional stimuli. Clinical correlation analysis showed that the history, attack frequency, duration, and neuropsychological scales of the migraine patients had a negative correlation with the network parameters in certain frequency ranges. Conclusions The results suggested that the individuals with migraine showed deviant effective connectivity in viewing the human facial expressions in multi-frequencies. The prefrontal-temporal pathway might be related to the altered negative emotional modulation in migraine. These findings suggested that migraine might be characterized by more universal altered cerebral processing of negative stimuli. Since the significant result in this study was frequency-specific, more independent replicative studies are needed to confirm these results, and to elucidate the neurocircuitry underlying the association between migraine and emotional conditions.

Evidence of the acute effects of air pollutants on ischemic heart disease (IHD) hospitalizations based on the entire population of a megacity in central China is lacking. All IHD hospitalization records from 2017 to 2018 were obtained from the Wuhan Information Center of Health and Family Planning. Daily air pollutant concentrations and meteorological data were synchronously collected from the Wuhan Environmental Protection Bureau. A time-series study using generalized additive models was conducted to systematically examine the associations between air pollutants and IHD hospitalizations. Stratified analyses by gender, age, season, hypertension, diabetes, and hyperlipidemia were performed. In total, 139,616 IHD hospitalizations were included. Short-term exposure to air pollutants was positively associated with IHD hospitalizations. The age group ≥76 was at higher exposure risk, and the associations appeared to be more evident in cold seasons. PM2.5 and PM10 appeared to have greater effects on males and those without hypertension or diabetes, whereas NO2 and SO2 had greater effects on females and those with hypertension or diabetes. The risk of IHD hospitalization due to air pollutants was greater in people without hyperlipidemia. Our study provides new evidence of the effects of air pollution on the increased incidence of IHD in central China.

Multiple myeloma is a heterogeneous plasma cell malignancy that remains incurable because of the tendency of relapse for most patients. Survival outcomes may vary widely due to patient and disease variables; therefore, it is necessary to establish a more accurate prognostic model to improve prognostic precision and guide clinical therapy. Here, we developed a risk score model based on myeloma gene expression profiles from three independent datasets: GSE6477, GSE13591, and GSE24080. In this model, highly survival-associated five genes, including EPAS1, ERC2, PRC1, CSGALNACT1, and CCND1, are selected by using the least absolute shrinkage and selection operator (Lasso) regression and univariate and multivariate Cox regression analyses. At last, we analyzed three validation datasets (including GSE2658, GSE136337, and MMRF datasets) to examine the prognostic efficacy of this model by dividing patients into high-risk and low-risk groups based on the median risk score. The results indicated that the survival of patients in low-risk group was greatly prolonged compared with their counterparts in the high-risk group. Therefore, the five-gene risk score model could increase the accuracy of risk stratification and provide effective prediction for the prognosis of patients and instruction for individualized clinical treatment.

Objective: Our aim was to investigate the dynamics of functional connectivity (FC) networks during seizure termination in patients with childhood absence epilepsy (CAE) using magnetoencephalography (MEG) and graph theory (GT) analysis.Methods: MEG data were recorded from 22 drug-naïve patients diagnosed with CAE. FC analysis was performed to evaluate the FC networks in seven frequency bands of the MEG data. GT analysis was used to assess the topological properties of FC networks in different frequency bands.Results: The patterns of FC networks involving the frontal cortex were altered significantly during seizure termination compared with those during the ictal period. Changes in the topological parameters of FC networks were observed in specific frequency bands during seizure termination compared with those in the ictal period. In addition, the connectivity strength at 250–500 Hz during the ictal period was negatively correlated with seizure frequency.Conclusions: FC networks associated with the frontal cortex were involved in the termination of absence seizures. The topological properties of FC networks in different frequency bands could be used as new biomarkers to characterize the dynamics of FC networks related to seizure termination.

Immune checkpoint inhibitors (ICIs) have made breakthrough progress in the treatment of various malignant tumors. However, only some patients receiving ICIs obtain long-lasting clinical effects, and some patients still do not achieve remission. Improving the treatment benefits of this part of the population has become a concern of clinicians. IL-1 signaling plays an important role in the tumor microenvironment (TME). However, the relationship between the IL-1 signaling mutation status and the prognosis of colon adenocarcinoma (COAD) patients receiving ICIs has not been reported. We downloaded the data of a COAD cohort receiving ICIs, including prognostic data and mutation data. Additionally, we downloaded the data of a COAD cohort from The Cancer Genome Atlas (TCGA) database, including clinical data, expression data and mutation data. Gene set enrichment analysis (GSEA) was used to assess differences in the activity of some key physiological pathways between the IL-1 signaling mutated-type (IL-1-MT) and IL-1 signaling wild-type (IL-1-WT) groups. The CIBERSORT algorithm was used to evaluate the contents of immune cells in the TME of COAD patients. The multivariate Cox regression model results suggested that IL-1-MT can be used as an independent predictor of a better prognosis in COAD patients receiving ICIs (P = 0.03, HR = 0.269, 95% CI: 0.082-0.883). Additionally, IL-1-MT COAD patients had significantly longer overall survival (OS) (log-rank P = 0.015). CIBERSORT analysis showed that the IL-1-MT group had high infiltration levels of activated dendritic cells (DCs), M1 macrophages, neutrophils, activated natural killer (NK) cells, activated CD4+ memory T cells and CD8+ T cells. Similarly, the IL-1-MT group had significantly upregulated immunogenicity, including in terms of the tumor mutation burden (TMB), neoantigen load (NAL) and number of mutations in DNA damage repair (DDR) signaling. GSEA showed that the IL-1-MT group was highly enriched in the immune response and proinflammatory mediators. Additionally, the expression levels of immune-related genes, immune checkpoint molecules and immune-related signatures were significantly higher in the IL-1-MT group than in the IL-1-WT group. IL-1-MT may be an independent predictor of a good prognosis in COAD patients receiving ICIs, with significantly longer OS in IL-1-MT COAD patients. Additionally, IL-1-MT was associated with significantly increased immunogenicity, activated immune cell and inflammatory mediator levels and immune response-related scores.

Background: The coronary atherosclerotic burden in patients with ST-segment elevation myocardial infarction (STEMI) has been identified as the main predictor of prognosis. However, the association of lipoprotein(a) [Lp(a)], a well-established proatherogenic factor, with atherosclerotic burden in patients with STEMI is unclear.Methods: In total, 1,359 patients who underwent percutaneous coronary intervention (PCI) for STEMI were included in analyses. Three prespecified models with adjustment for demographic parameters and risk factors were evaluated. Generalized additive models and restricted cubic spline analyses were used to assess the relationships of Lp(a) with Gensini scores and the no-reflow phenomenon. Kaplan–Meier curves were generated to explore the predictive value of Lp(a) for long-term all-cause mortality. Furthermore, mRNA expression levels of LPA in different groups were compared using the GEO database.Results: Patients in the highest tertile according to Lp(a) levels had an increased incidence of heart failure during hospitalization. Furthermore, patients with high levels of Lp(a) (>19.1 mg/dL) had sharply increased risks for a higher Gensini score (Pfor trend = 0.03) and no-reflow (Pfor trend = 0.002) after adjustment for demographic parameters and risk factors. During a median follow-up of 930 days, 132 deaths (9.95%) were registered. Patients with high levels of Lp(a) (>19.1 mg/dL) had the worst long-term prognosis (Pfor trend < 0.0001). In a subgroup analysis, patients with higher Lp(a) still had the highest all-cause mortality. Additionally, the mRNA expression levels of LPA in patients with STEMI with lower cardiac function were higher than those in other groups (P = 0.003). A higher coronary atherosclerotic burden was correlated with higher LPA expression (P = 0.01).Conclusion: This study provides the first evidence that Lp(a) (at both the protein and mRNA levels) is independently associated with coronary atherosclerotic lesions and prognosis in patients with STEMI treated with PCI.Clinical Trial Registration:http://www.chictr.org.cn/index.aspx, identifier: ChiCTR1900028516.

Summary: Repaglinide (RPG) is a short-acting insulin secretagogue widely prescribed for the treatment of type 2 diabetes. It boosts insulin secretion by inhibiting the pancreatic ATP-sensitive potassium channel (KATP). However, the mechanisms by which RPG binds to the KATP channel are poorly understood. Here, we describe two cryo-EM structures: the pancreatic KATP channel in complex with inhibitory RPG and adenosine-5’-(γ-thio)-triphosphate (ATPγS) at 3.3 Å and a medium-resolution structure of a RPG-bound mini SUR1 protein in which the N terminus of the inward-rectifying potassium channel 6.1 (Kir6.1) is fused to the ABC transporter module of the sulfonylurea receptor 1 (SUR1). These structures reveal the binding site of RPG in the SUR1 subunit. Furthermore, the high-resolution structure reveals the complex architecture of the ATP binding site, which is formed by both Kir6.2 and SUR1 subunits, and the domain-domain interaction interfaces. : Ding et al. report the detailed binding site and the inhibitory mechanism of the insulin secretagogue repaglinide on the pancreatic KATP channel, revealed by a 3.3 Å cryo-EM structure and electrophysiology experiments. Keywords: diabetes, KATP channel, repaglinide, glibenclamide, sulfonylurea, glinides, Kir, SUR, ABC transporter, KNtp

Fat deposition in muscle includes intramuscular fat (IMF) and intermuscular fat. IMF content is an index of pork quality; however, because IMF content is difficult to measure in vivo in young animals, conventional breeding for IMF content is difficult to carry out. The mechanism and progression of animal fat deposition is not well understood, and there are currently no effective control methods. In this study, using Laiwu and large white pigs as the research subjects and RNA sequencing technology, we analyzed the genetic mechanism of animal fat deposition in pigs. Specifically, we analyzed the features of lncRNAs and their potential target genes. We obtained 464 million clean reads, from which 907 lncRNAs were identified. The cis and trans analysis identified target genes, including genes that were upregulated (286) and downregulated (621) in the fatty and lean pigs. ENSSSCG00000008692_ADD1, ENSSSCG00000023124_ADD1 and ENSSSCG00000005918_DGAT1 were validated as target genes of the lncRNAs and were shown to be closely related to fat deposition. These results provide a basis for studying the different metabolic lncRNA expression of IMF deposition. In addition, as the valuable model animal to study the mechanisms of obesity, pigs may represent a new avenue for studying human obesity.

Age-related cataract (ARC) is the most common cause of severe visual impairment and blindness. The precise mechanisms of ARC are not completely understood, but it is well accepted that oxidative damage plays an important role in the disease pathogenesis. BLM, the key enzyme of the double-strand break repair (DSBR) pathway, is part of a family of DNA unwinding enzymes and has a crucial role in multiple steps of the DNA recombination, replication and repair processes. We have recently shown that BLM-rs1063147 is initially associated with nuclear ARC in a cross-section study. Therefore, we wanted to study the effects of BLM on ARC progression. In ARC patients, BLM transcription in lens capsules was decreased, so did the BLM protein, and after UVB irradiation, BLM mRNA and protein levels were increased in SRA01/04 cells. Upon silencing BLM in SRA01/04 cells and rat lens, cell vitality and apoptosis were altered, and the rat lens opacification was considerable. In conclusion, BLM can regulate cataract progression by influencing cell vitality and apoptosis.

High-frequency oscillations (HFOs) are spontaneous magnetoencephalography (MEG) patterns that have been acknowledged as a putative biomarker to identify epileptic foci. Correct detection of HFOs in the MEG signals is crucial for the accurate and timely clinical evaluation. Since the visual examination of HFOs is time-consuming, error-prone, and with poor inter-reviewer reliability, an automatic HFOs detector is highly desirable in clinical practice. However, the existing approaches for HFOs detection may not be applicable for MEG signals with noisy background activity. Therefore, we employ the stacked sparse autoencoder (SSAE) and propose an SSAE-based MEG HFOs (SMO) detector to facilitate the clinical detection of HFOs. To the best of our knowledge, this is the first attempt to conduct HFOs detection in MEG using deep learning methods. After configuration optimization, our proposed SMO detector is outperformed other classic peer models by achieving 89.9% in accuracy, 88.2% in sensitivity, and 91.6% in specificity. Furthermore, we have tested the performance consistency of our model using various validation schemes. The distribution of performance metrics demonstrates that our model can achieve steady performance.

We studied the effects of leaf surface characteristics on canopy droplet behaviour using two rice cultivars with similar leaf shapes but significantly different leaf surface characteristics: Jia58 (glabrous rice; smooth leaf surface and no burrs) and Yongyou12 (hairy-leaved rice; rough leaf surface covered with burrs). The plants were subjected to spray tests with different spray pressures and nozzle apertures. The results show that the deposition amount per unit leaf area was significantly higher in the Yongyou12 canopy than in the Jia58 canopy. The diameter, volume median diameter, number median diameter, and coverage of droplets were significantly higher in Yongyou12 than in Jia58, while the coverage density of droplets was significantly lower. The proportion of small droplets of Jia58 is higher than that of Yongyou12. Thus, a larger amount of large-sized droplets could retain on the leaf surface of hairy-leaved rice, and a larger number of small-sized droplets were retained on the leaf surface of glabrous rice. Smaller pressure and larger flow nozzle were conducive to the retention of the Jia58, while Yongyou12 required larger pressure and larger flow nozzles. Ultrastructural analyses revealed that the leaf surface of glabrous rice had no trichomes and more wax than hairy-leaved rice, and the critical surface tension was lower, resulting in the retention of mainly small droplets on its leaf surface and a lower deposition amount. Therefore, in order to increase the deposition of pesticide droplets on the leaf surface in production, glabrous rice should choose nozzles with smaller spray pressure and large flow rate.

BACKGROUND: To explore the diagnostic value of epidermal growth factor receptor (EGFR) and structural maintenance of chromosome protein 4 (SMC4) for triple-negative breast cancer. METHODS: A total of 213 breast cancer patients were selected and divided into triple-negative breast cancer (100 cases) and non-triple-negative breast cancer (113 cases) according to the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Patient information including age, body mass index (BMI), smoking history, drinking history, menopause, tumor classification, lymph node metastasis, distant metastasis, clinical stage, and EGFR and SMC4 expression were collected for all subjects. Logistic regression analysis was then used to evaluate the risk factors for triple-negative breast cancer. The ROC curve was also used to evaluate the clinical value of EGFR and SMC4 in the diagnosis of triple-negative breast cancer. RESULTS: Logistic regression analysis showed that high expression of SMC4 and high expression of EGFR were both risk factors for triple-negative breast cancer, with an odds ratio (OR) of 1.72 and 1.56, respectively (both P

TRPC5 channel is a nonselective cation channel that participates in diverse physiological processes. TRPC5 inhibitors show promise in the treatment of anxiety disorder, depression, and kidney disease. However, the binding sites and inhibitory mechanism of TRPC5 inhibitors remain elusive. Here, we present the cryo-EM structures of human TRPC5 in complex with two distinct inhibitors, namely clemizole and HC-070, to the resolution of 2.7 Å. The structures reveal that clemizole binds inside the voltage sensor-like domain of each subunit. In contrast, HC-070 is wedged between adjacent subunits and replaces the glycerol group of a putative diacylglycerol molecule near the extracellular side. Moreover, we found mutations in the inhibitor binding pockets altered the potency of inhibitors. These structures suggest that both clemizole and HC-070 exert the inhibitory functions by stabilizing the ion channel in a nonconductive closed state. These results pave the way for further design and optimization of inhibitors targeting human TRPC5.

AIM: To observe the protective effect of human umbilical cord mesenchymal stem cells (hucMSCs) on retinal ganglion cells (RGCs) injury in mice with acute ocular hypertension (AOH). METHODS: Fifty-six adult male C57BL/6 mice were randomly divided into four groups: normal group, AOH group, hucMSCs group, normal saline (NS) group. Left eye of mice was induced by 90 mm Hg intraocular pressure for 1h to establish AOH model. hucMSCs 1×105/µL, 1 µL or NS 1 µL was injected into the vitreous body the next day. CM-Dil fluorescent dye was used to label the 3rd generation of hucMSCs, for tracing the cells in the vitreous cavity of mice. Seven days after the model established, hematoxylin-eosin (HE) staining was used to observe the thickness of the inner retina layer in four groups. Numbers and loss rate of RGCs were evaluated by counting Brn-3a positive cells stained by immunofluorescencein. RESULTS: On the 7th day after AOH established, labeled hucMSCs were found in the vitreous cavity. HE staining showed that the thickness of retinal inner layer in AOH group was significantly lower than that in normal group and hucMSCs group (P0.05). Compared with AOH group, the RGCs in normal group was significantly higher; RGCs number increased in hucMSCs group and the loss rate was lower (P

Determination of the optimal fertilization method is crucial to maximize nitrogen use efficiency and yield of different rice cultivars. Side-deep fertilization with controlled-release nitrogen, in conjunction with machine transplanting and subsequent topdressing, was applied to Indica–japonica hybrid rice ‘Yongyou1540’ (YY1540) and indica hybrid rice ‘Tianyouhuazhan’ (TYHZ). Four nitrogen treatments were applied in 2018 and 2019: traditional nitrogen application with quick-release nitrogen (T1), single-dose deep fertilization at transplanting with 100% controlled-release nitrogen (T2), and deep fertilization of 70% controlled-release nitrogen and topdressing of 30% quick nitrogen at tillering (T3), or at panicle initiation (T4). Side-deep fertilization reduced the fertilizer application frequency without causing yield loss, T4 enhanced the yield of YY1540 by increasing the number of productive tillers and number of spikelets per panicle compared with T1, T2 and T3. The yield of TYHZ showed no significant difference among treatments. The T4 treatment decreased the number of tillers at the tilling peak stage and increased the percentage productive tillers and number of differentiated spikelets. Compared with the other treatments, T4 increased dry matter accumulation and leaf area index during panicle initiation and grain ripening, and contributed to enhanced nitrogen uptake and nitrogen utilization in YY1540. On average, nitrogen uptake and utilization in YY1540 were highest in T4, but no significant differences among treatments were observed in TYHZ. Dry matter accumulation and nitrogen uptake from panicle initiation to heading of YY1540 were correlated with number of spikelets per panicle, but no significant correlations were observed for TYHZ. Supplementary topdressing with quick-release nitrogen at the panicle initiation stage was required to increase yield of indica–japonica hybrid rice, whereas single-dose deep fertilization with controlled-release nitrogen is satisfactory for the indica hybrid cultivar.

Age-related cataract (ARC) is a progressive lens opacification that occurs from middle to old age. Eph-receptor tyrosinekinase-type A2 (EphA2) has been reported to be associated with ARC. This work aims to investigate the molecular mechanism of EphA2 in ARC. We treated human lens epithelial cells (SRA01/04) with different concentration of H2O2 to induce lens epithelial cell damage. Then, we found that H2O2 treatment significantly suppressed cell viability and enhanced the expression of EphA2 in the SRA01/04 cells. H2O2 treatment repressed cell viability and enhanced the levels of reactive oxygen species (ROS) in SRA01/04 cells, which was partly abolished by EphA2 up-regulation. Moreover, EphA2 overexpression reduced H2O2-induced apoptosis of SRA01/04 cells. EphA2 up-regulation caused an up-regulation of Bcl-2, and repressed the expression of Bax and Cleaved-caspase-3 in the SRA01/04 cells following H2O2 treatment. In conclusion, our data confirm that EphA2 overexpression enhances cell viability and inhibits apoptosis in the H2O2-treated SRA01/04 cells, thereby reducing H2O2-induced damage of lens epithelial cells. Thus, this work provides new insights into the mechanism of EphA2 in ARC.

Magnetoencephalography (MEG) is a persuasive tool to study the human brain in physiology and psychology. It can be employed to obtain the inference of change between the external environment and the internal psychology, which requires us to recognize different single trial event-related magnetic fields (ERFs) originated from different functional areas of the brain. Current recognition methods for the single trial data are mainly used for event-related potentials (ERPs) in the electroencephalography (EEG). Although the MEG shares the same signal sources with the EEG, much less interference from the other brain tissues may give the MEG an edge in recognition of the ERFs. In this work, we propose a new recognition method for the single trial auditory evoked magnetic fields (AEFs) through enhancing the signal. We find that the signal strength of the single trial AEFs is concentrated in the primary auditory cortex of the temporal lobe, which can be clearly displayed in the 2D images. These 2D images are then recognized by an artificial neural network (ANN) with 100% accuracy, which realizes the automatic recognition for the single trial AEFs. The method not only may be combined with the source estimation algorithm to improve its accuracy but also paves the way for the implementation of the brain-computer interface (BCI) with the MEG.