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Background Brahma-related gene 1 (BRG1) is essential for embryogenesis and cellular metabolism. A deficiency of BRG1 in vivo decreases lipid droplets, but the molecular mechanism underlying its role in lipid metabolism associated with hepatocellular carcinoma (HCC) remains unknown. Aims We aimed to determine the role of BRG1 in lipid metabolism in HCC. Methods We assessed the differential expression of BRG1 in HCC and adjacent non-tumorous tissues using tissue microarrays. We stained lipid droplets in HCC cells with Bodipy fluorescence and Oil Red O, and verified BRG1 binding to the promoter region of glycosylated lysosomal membrane protein (GLMP) using chromatin immunoprecipitation. Results The expression of GLMP, a potential lipid metabolism regulator, was suppressed by BRG1 via transcriptional activity. Knockdown of BRG1 decreased lipid droplets, increased GLMP expression and altered the phosphoinositide-3-kinase adaptor protein 1 (PIK3AP1)/phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT) pathway in HCC, which further GLMP knockdown partially restored. Thus, GLMP knockdown increased lipid droplets and differentially altered the PI3K/AKT pathway. Conclusions Downregulating BRG1 decreased lipid droplet deposition in HCC cells by upregulating GLMP and altering the PI3K/AKT pathway. Both BRG1 and GLMP might serve as therapeutic targets for disorders associated with dysregulated lipid metabolism, such as NAFLD and NAFLD-associated HCC.

Although general anesthetics have been used in the clinic for more than 170 years, the ways in which they induce amnesia, unconsciousness, analgesia, and immobility remain elusive. Modulations of various neural nuclei and circuits are involved in the actions of general anesthetics. The expression of the immediate early gene c-fos and its nuclear product, c-fos protein can be induced by neuronal depolarization; therefore, c-fos staining is commonly used to identify the activated neurons during sleep and/or wakefulness, as well as in various physiological conditions in the central nervous system. Identifying c-fos expression is also a direct and convenient method to explore the effects of general anesthetics on the activity of neural nuclei and circuits. Using c-fos staining, general anesthetics have been found to interact with sleep- and wakefulness-promoting systems throughout the brain, which may explain their ability to induce unconsciousness and emergence from general anesthesia. This review summarizes the actions of general anesthetics on neural nuclei and circuits based on c-fos expression.

Conductive filaments (CFs) play a critical role in the mechanism of resistive random-access memory (ReRAM) devices. However, in situ detection and visualization of the precise location of CFs are still key challenges. We demonstrate for the first time the use of a π-conjugated molecule which can transform between its twisted and planar states upon localized Joule heating generated within filament regions, thus reflecting the locations of the underlying CFs. Customized patterns of CFs were induced and observed by the π-conjugated molecule layer, which confirmed the hypothesis. Additionally, statistical studies on filaments distribution were conducted to study the effect of device sizes and bottom electrode heights, which serves to enhance the understanding of switching behavior and their variability at device level. Therefore, this approach has great potential in aiding the development of ReRAM technology. Agency for Science, Technology and Research (A*STAR) Ministry of Education (MOE) Accepted version The authors acknowledge funding support from A*STAR AME IAF-ICP (grant no. I1801E0030) grant. This work is also supported by Ministry of Education (MOE) under AcRF Tier 2 grants (2019-T2-2-106, 2019-T2-2-066) and the National Robotics Programme (W1925d0106).

Accurately predicting energy consumption (EC) is a difficult task, owing to its inherent complexity and nonlinearity features. To decrease the complexity of EC predictions, applying a novel three-layer decomposition approach to decompose a complex series into a trend sub-series and several simpler non-trend sub-series. Since the trend sub-series describes the developing tendency that is determined by the primarily influencing factors on EC, it is predicted by multivariate linear regression (MLR). In view of its learning ability of nonlinear mappings and excellent performance in dealing with long term dependency, long short-term memory neural network (LSTM) is applied to predict non-trend sub-series. Then, the final EC prediction is solved by calculating the sum of all these sub-series prediction values. A novel EC forecasting model based on machine learning with three-layer decomposition-ensemble approach is proposed in this study. Compared with traditional decomposition approaches (trend decomposition (TD), wavelet decomposition (WD), empirical mode decomposition (EMD), TD-EMD and TD-WD), the proposed three-layer decomposition approach can improve the prediction performance by combining the advantages of TD, EMD and WD. The proposed forecasting model is validated by empirical studies using the EC data of China and U.S. Finally, this study gives the China’s EC prediction in 2020–2024.

Aggressive behavior is important for animals to obtain limited resources. Understanding fish behavior and physiological response is of great significance to evaluate aquaculture production and fish welfare. Food is an important trigger of aggressive behavior in juvenile fish under high-density aquaculture conditions. The aim of this study was to investigate the aggressive behavior and monoamine levels of juvenile pufferfish (mean body mass of 6.29 ± 0.33 g) under normal feeding and restricted feeding. Our main results included the following: (1) The mortality and fin damage were higher and aggression was more intense of juvenile pufferfish at the 1% ration than those of the 3% ration; (2) during feeding, the velocity, body contact, and activity at the 1% ration were significantly higher than that of the 3% ration; (3) the concentrations of brain 5-hydroxyindoleacetic acid (5-HIAA) and monoamine oxidase A (MAOA) at the 1% ration were significantly lower, and dopamine (DA) concentrations were significantly higher. These results suggest that juvenile pufferfish shows serious aggressive behavior at the low ration, which may be related to the decrease of 5-HIAA and MAOA concentrations, and the increase of DA concentrations.

Background: The widely divergent responsiveness of Parkinson’s disease (PD) patients to levodopa is an important clinical issue because of its relationship with quality of life and disease prognosis. Preliminary animal experiments have suggested that degeneration of the locus coeruleus (LC) attenuates the efficacy of levodopa treatment. Objective: To explore the relationship between LC degeneration and levodopa responsiveness in PD patients in vivo. Methods: Neuromelanin-sensitive magnetic resonance imaging (NM-MRI), a good indicator of LC and substantia nigra (SN) degeneration, and levodopa challenge tests were conducted in 57 PD patients. Responsiveness to levodopa was evaluated by the rates of change of the Unified Parkinson’s Disease Rating Scale Part III score and somatomotor network synchronization calculated from resting-state functional MRI before and after levodopa administration. Next, we assessed the relationship between the contrast-to-noise ratio of LC (CNRLC) and levodopa responsiveness. Multiple linear regression analysis was conducted to rule out the potential influence of SN degeneration on levodopa responsiveness. Results: A significant positive correlation was found between CNRLC and the motor improvement after levodopa administration (R = 0.421, p = 0.004). CNRLC also correlated with improvement in somatomotor network synchronization (R = –0.323, p = 0.029). Furthermore, the relationship between CNRLC and levodopa responsiveness was independent of SN degeneration. Conclusion: LC degeneration might be an essential factor for levodopa resistance. LC evaluation using NM-MRI might be an alternative tool for predicting levodopa responsiveness and for helping to stratify patients into clinical trials aimed at improving the efficacy of levodopa.

Alopecia areata (AA) is a common chronic tissue-specific autoimmune disease, resulting in hair loss, that affects up to 2% of the general population. The exact pathobiology of AA has still remained elusive, while the common theory is the collapse of the immune privilege of the hair follicle caused by immunological mechanism. Multiple genetic and environment factors contribute to the pathogenesis of AA. There are several clinical treatments for AA, varying from one or multiple well-defined patches to more diffuse or total hair loss of the scalp (alopecia totalis) or hair loss of the entire body (alopecia universalis). The available treatments for AA, such as corticosteroids and other immunomodulators, minoxidil, and contact immunotherapy, are of limited efficacy with a high risk of adverse effects and high recurrence rates, especially for patients with severe AA. Recent insights into the pathogenesis of AA have led to the development of new treatment strategies, such as Janus kinase (JAK) inhibitors, biologics, and several small molecular agents. In addition, modern therapies for AA, including antihistamines, platelet-rich plasma (PRP) injection, and other novel therapies have been well explored. In this review, we discussed the recent advances in the pathogenesis, diagnosis, and treatment of AA.

Nettings are complex flexible structures used in various fisheries. Understanding the hydrodynamic characteristics, deformation, and the flow field around nettings is important to design successful fishing gear. This study investigated the hydrodynamic characteristics and deformation of five nettings made of polyethylene and nylon materials in different attack angles through numerical simulation and physical model experiment. The numerical model was based on the one-way coupling between computational fluid dynamics (CFD) and large deflection nonlinear structural models. Navier-Stokes equations were solved using the finite volume approach, the flow was described using the k-ω shear stress turbulent model, and the large deflection structural dynamic equation was derived using a finite element approach to understand the netting deformation and nodal displacement. The porous media model was chosen to model the nettings in the CFD solver. Numerical data were compared with the experimental results of the physical model to validate the numerical models. Results showed that the numerical data were compatible with the experimental data with an average relative error of 2.34%, 3.40%, 6.50%, and 5.80% in the normal drag coefficients, parallel drag coefficients, inclined drag coefficients, and inclined lift coefficients, respectively. The hydrodynamic forces of the polyethylene and nylon nettings decreased by approximately 52.56% and 66.66%, respectively, with decreasing net solidity. The drag and lift coefficients of the nylon netting were approximately 17.15% and 6.72% lower than those of the polyethylene netting. A spatial development of turbulent flow occurred around the netting because of the netting wake. However, the flow velocity reduction downstream from the netting in the wake region increased with increasing attack angle and net solidity. In addition, the deformation, stress, and strain on each netting increased with increasing solidity ratio.

Background Nocardiosis is an uncommon infection that usually occurs in immunocompromised patients, and the pulmonary system is the most common site. We report an uncommon case of nocardiosis with diffuse involvement of the pleura, which presented as multiple localized nodular or hillock lesions on computed tomography (CT) with local chest wall infiltration. Case summary A 54-year-old woman was referred to our hospital due to cough and fever for 20 d. She had a history of nephrotic syndrome for 7 mo and was given prednisone (60 mg/d) 6 mo previously. The hormone was then gradually reduced to the current dose of 25 mg/d. Chest CT showed many nodular or hillock lesions in the right pleura, mediastinum, and interlobar fissure areas. On the lower layer, one lesion infiltrated the chest wall. She was treated with piperacillin sodium and sulbactam sodium, but the therapeutic effect was not good. In this regard, ultrasound-guided local infiltration anesthesia was further conducted for perihepatic hydrops drainage to improve diagnostic accuracy. Puncture fluid culture isolated Nocardia species, confirming the diagnosis of nocardiosis. Subtype Nocardia farcinica was identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Antibiotic treatment was switched to trimethoprim/sulfamethoxazole and imipenem. After 8 d of treatment, the patient was discharged from the hospital with improved condition, and she has been recurrence-free for 2 years. Conclusion This report illustrates that nocardiosis should be suspected when clinicians encounter patients who are immunocompromised and have diffuse involvement of the pleura.

Background The calcification sign assessed by computed tomography appears to be a potential marker for benignities among patients diagnosed with pulmonary nodules (PNs). The following meta-analysis has been purposefully designed to figure-out the diagnostic value of the calcification signature as a way of identifying benignities from PNs. Methods Cochrane Library, Embase and PubMed were considered as a reference to obtain the required data from January 2000 until October 2020. Stata v12.0 was used as a standard tool for statistical assessment. Results Eleven retrospective studies were assessed via this meta-analysis, which included 6136 PNs (1827 benign and 4309 malignant). The pooled diagnostic odd ratios, positive likelihood ratio (PLR), negative likelihood ratio (NLR), sensitivity and specificity were 6.79, 6.06, 0.89, 13% and 98%, respectively. The value obtained for the area under the curve was 0.65, showing moderate overall diagnostic accuracy. A significant heterogeneity was found while calculating the pooled sensitivity (I2 = 85.5%), specificity (I2 = 75.0%), PLR (I2 = 59.0%), NLR (I2 = 79.5%) and DOR (I2 = 100.0%) in the current analysis. Sub-group analyses presented better PLR and specificity values for the study with a sample size ≥ 400. Deeks' funnel plot asymmetry test detected no potential evidence of significant publication bias (p = 0.091). Conclusions Calcification signs have been identified as moderate regulators corresponding to overall diagnostic performance (via marking a distinct differentiation between malignant and benign) for PNs. However, the manifestation of the calcification sign had a good directive property for benign PNs.

To explore the microstructural alterations in subcortical nuclei in Parkinson's disease (PD) at different stages with diffusion kurtosis imaging (DKI) and tensor imaging and to test the performance of diffusion metrics in identifying PD.108 PD patients (64 patients in early-stage PD group (EPD) and 44 patients in moderate-late-stage PD group (MLPD)) and 64 healthy controls (HC) were included. Tensor and kurtosis metrics in the subcortical nuclei were compared. Partial correlation was used to correlate the diffusion metrics and Unified Parkinson's Disease Rating Scale part-III (UPDRS-III) score. Logistic regression and receiver operating characteristic analysis were applied to test the diagnostic performance of the diffusion metrics.Compared with HC, both EPD and MLPD patients showed higher fractional anisotropy and axial diffusivity, lower mean kurtosis (MK) and axial kurtosis in substantia nigra, lower MK and radial kurtosis (RK) in globus pallidus (GP) and thalamus (all p 0.05). Compared with EPD, MLPD patients showed lower MK and RK in GP and thalamus (all p 0.05). MK and RK in GP and thalamus were negatively correlated with UPDRS-III score (all p 0.01). The logistic regression model combining kurtosis and tensor metrics showed the best performance in diagnosing PD, EPD, and MLPD (areas under curve were 0.817, 0.769, and 0.914, respectively).PD has progressive microstructural alterations in the subcortical nuclei. DKI is sensitive to detect microstructural alterations in GP and thalamus during PD progression. Combining kurtosis and tensor metrics can achieve a good performance in diagnosing PD.

To explore the feasibility of the fetal heart quantitative technique (fetalHQ) for evaluating the sphericity index (SI) of the fetal heart during middle and late pregnancy.Ninety-six normal fetuses in middle and late gestation who underwent systemic ultrasound examination in the Department of Ultrasound of the Maternal and Child Health Care Hospital of Hunan Province in November 2020 were enrolled, and dynamic images of the four-chamber view of the fetal heart were collected. The correlation between the global sphericity index (GSI), ventricular 24-segment SI, and gestational age (GA) was analyzed, and the differences between the left and right ventricular 24-segment SI were compared.The success rate of fetalHQ analysis was 93.75%. There was no significant linear correlation between GSI and ventricular 24-segment SI and GA (allFetalHQ is a simple and reliable method for evaluating the GSI and 24-segment SI of the left and right ventricles. It can provide some theoretical basis for the clinical quantitative evaluation of fetal heart geometry and lay a foundation for the quantitative evaluation of fetal heart function in cases of structural and functional abnormalities.

Background Gastric cancer (GC) is one of the most prevalent cancers globally with a poor prognosis. The progesterone receptor gene (PGR), which encodes the progesterone receptor (PR), can modulate the immune response in many cancers, but its correlation with prognosis and immune infiltration in GC remains unclear. We aimed to investigate the relationship between PGR expression and prognosis in GC patients. Methods The expression profile was obtained and the relationship between PGR expression and cancer prognosis was analyzed by Oncomine, Tumor Immune Estimation Resource (TIMER), Kaplan-Meier plotter, the PrognoScan database and Gene Expression Profiling Interactive Analysis (GEPIA) database using the minimum P value approach and log-rank method for prognosis analysis. Next, the correlation between the expression level of PGR and immune cell infiltration by the Spearman method using TIMER and GEPIA. Results A correlation of elevated PGR expression with poorer prognosis in GC was observed, with overall survival (OS) hazard ratio (HR) was 1.74 [95% confidence interval (CI): 1.4–2.17, P value =6.2e-7] and progression-free survival (PFS) HR was 2.09 (95% CI: 1.58–2.78, P value =1.6e-7). Also, high expression of PGR was related to worse OS and PFS in patients of each N stage in GC, with the highest OS and PFS HR values in stage N1. PGR expression in stomach adenocarcinoma (STAD) was significantly correlated with levels of B cells, CD8+T cells, CD4+T cells, macrophages, neutrophils and dendritic cells. It was also observed that PGR expression was related to a variety of immune cell markers. Conclusions PGR expression correlated with prognosis and immune cell infiltration in GC, indicating PGR is a potential prognostic biomarker in GC patients.

Orofacial ectopic pain can often arise following nerve injury. However, the exact mechanism responsible for orofacial ectopic pain induced by trigeminal nerve injury remains unknown. The α2δ-1 and glutamate N-methyl- d -aspartic acid receptor (NMDAR) interactions have been demonstrated to participate in neuropathic pain regulation in the spinal cord. In this study, a rat model of inferior alveolar nerve transection (IANX) was used to investigate the role of α2δ-1-NMDAR1 interaction in the trigeminal ganglion (TG) in regard to the regulation of orofacial ectopic pain. Western blot (WB) analysis indicated that α2δ-1 and NMDAR1 in the TG were substantially higher in IANX rats than they were in sham/naive rats. Additionally, immunofluorescence (IF) results revealed that α2δ-1 and NMDAR1 were co-expressed and distributed within neurons and activated satellite glial cells in the TG. Co-immunoprecipitation (Co-IP) results indicated that α2δ-1-NMDAR1 complex levels in the TG were higher in IANX rats than they were in sham rats. Furthermore, the results of behavioral tests demonstrated that intra-TG injection of gabapentin (α2δ-1 inhibitory ligand) or memantine hydrochloride (NMDAR antagonist) reversed the decrease in mechanical head-withdrawal threshold (HWT) in IANX rats. Moreover, inhibition of α2δ-1 by intra-TG administration of gabapentin suppressed the upregulation of the NMDAR1 protein, and the inhibition of NMDAR by intra-TG administration of memantine hydrochloride inhibited the increased expression of α2δ-1 protein induced by IANX. In conclusion, the physical and functional interaction between α2δ-1 and NMDAR1 is critical for the development of orofacial ectopic pain, indicating that α2δ-1, NMDAR1, and the α2δ-1–NMDAR1 complex may represent potential targets for the treatment of orofacial ectopic pain.

BACKGROUND Excessive iron accumulation is one of the main pathogeneses of Parkinson's disease (PD). Ceruloplasmin plays an important role in keeping the iron homoeostasis. PURPOSE To explore the association between serum ceruloplasmin depletion and subcortical iron distribution in PD. STUDY TYPE Prospective. POPULATION One hundred and twenty-one normal controls, 34 PD patients with low serum ceruloplasmin (PD-LC), and 28 patients with normal serum ceruloplasmin (PD-NC). SEQUENCE Enhanced susceptibility-weighted angiography (ESWAN) on a 3 T scanner. ASSESSMENT Quantitative susceptibility mapping was employed to quantify the regional iron content by using a semi-automatic method. Serum ceruloplasmin concentration was measured from peripheral blood sample. Clinical assessments were conducted by a neurologist. STATISTICAL TESTS General linear model was used to compare the intergroup difference of region iron distribution among groups, and the statistics was adjusted by Bonferroni method (P

Background Graft vascular disease (GVD) is the main reason of late transplanted organ failure, which limits the long-term survival of patients. Murine aortic transplant is widely used in the field to understand the mechanisms leading to GVD. Currently, 3 major techniques, end-to-end anastomosis, sleeve suture and cuff technology, have been used to study the mechanism of GVD. However, which method is more suitable in mouse model of GVD? Herein, we compared these 3 surgical techniques in a mouse allograft arteriosclerosis model to determine the technique with the most appreciable outcomes. Methods Male C57Bl/6 (H-2b) and BALB/c (H-2d) mice were used for aorta transplantation with these 3 techniques. These 3 techniques were compared with regard to donor artery acquisition time, artery anastomosis time, overall surgical time, the amount of bleeding of each technique and the success rate of surgery. Hematoxylin and eosin (H&E) and Masson staining were used to examine the pathological changes of grafted vessels. The protein expression of phospho-NF-κb P65 and PCNA were determined to validate laminar flow and proliferative capacity of neointima obtained from different surgical and control groups. Results Sleeve suture had a shorter vascular anastomosis time and total operation time than end-to-end anastomosis and cuff technique. Sleeve suture and cuff technique had significantly fewer amount of bleeding from the site of vascular anastomosis than end-to-end anastomosis. Moreover, sleeve suture had the highest success rate among these 3 techniques. There was no difference in the degree of graft stenosis and collagen deposition between these 3 techniques. In addition, there was no significant difference in the expression of phospho-NF-κb P65and PCNA between the experimental group. Conclusions Sleeve suture is superior to end-to-end anastomosis and cuff technique with regard to vascular grafting in the murine model.

Cheng Zhou,1 Chunlin Song,1 Xiang Huang,1 Shufen Chen,1 Yan Long,2 Shanshui Zeng,2 Hongling Yang,2 Min Jiang2 1Laboratory of Molecular Diagnostics, Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan, Foshan, 528000, People’s Republic of China; 2Department of Laboratory, Guangzhou Women and Children’s Medical Centre, Guangzhou Medical University, Guangzhou, 510623, People’s Republic of ChinaCorrespondence: Hongling Yang; Min JiangDepartment of Laboratory, Guangzhou Women and Children’s Medical Centre, Guangzhou Medical University, No. 9, Jinsui Road, Guangzhou, 510623, People’s Republic of ChinaTel +86-20-38857723; +86-20-38076256Email hlyang62@163.com; jiangmin2011@126.comBackground: Gestational hypertension (GH), a hypertensive disorder of pregnancy (HDP), is a leading cause of maternal and fetal mortality due to the lack of clarity on its exact etiology and clinically feasible prediction models. This study was performed to discover novel biomarkers before 20 weeks gestation and thereby construct an early GH prediction model.Methods: This study was designed based on differentially expressed protein screening followed by clinical validation. In the screening phase, a nested case-controlled study was conducted by plasma proteomic analyses using label-free LC-MS/MS and plasma samples from seven pre-GH cases before 20-week gestation and seven age- and gestational week-matched controls. In the validation phase, 10 proteins with differential expression in the screening phase were validated by ELISA or electrochemiluminescence in an independent study consisting of 29 pre-GH cases before 20-week gestation and 29 matched controls.Results: In the screening phase, 149 proteins were found to be differentially expressed between the two groups and were predominantly involved in complement and coagulation cascades, platelet degranulation and positive regulation of cell motility. Further validation showed that serpin family C member 1 (SERPINC1), serpin family A member 5 (SERPINA5), complement factor H-related protein 5 (CFHR5), clusterin, cytokeratin 18 (CK18) and histidine-rich glycoprotein (HRG) levels were significantly higher in women who later developed GH compared to women with uncomplicated pregnancies (P< 0.05). Binary logistic regression analysis was used to determine the combination efficacy of models for early prediction of GH. The model with a combination of SERPINC1, CK18 and HRG had a significantly better discriminatory power (AUC = 0.91, 95% CI 0.83– 0.98) compared to the models with those proteins alone as independent predictors of GH.Conclusion: Plasma levels of SERPINC1, SERPINA5, CFHR5, clusterin, CK18 and HRG are potential novel predictive biomarkers of GH, and a prediction model using a combination of SERPINC1, CK18 and HRG has good discriminatory performance for GH before 20 weeks gestation.Keywords: label-free LC-MS/MS, gestational hypertension, biomarkers

An internal-and-external-cavity Fabry–Perot interferometer (IECFPI) model was mathematically constructed. Based on the IECFPI configuration, a crosstalk-free fiber optic sensor for simultaneous measurement of refractive index (RI) and temperature was proposed and experimentally demonstrated. The internal cavity was a silica cavity, while the external one consisted of an open cavity and silica cavity. The open cavity was formed by an offset single-mode fiber (SMF) sandwiched between two sections of SMF, and the silica cavity was formed by a well-cleaved SMF. A sensitivity coefficient (SC) matrix of the proposed sensor was used to determine the RI and temperature by monitoring the wavelength shifts of the envelope and fine fringes. The proposed sensor can be used for simultaneous measurement of RI and temperature based on the inverse of the SC matrix. Experimental results demonstrated that the RI sensitivities for the envelope and fine fringes were 1084.9 and 124.2 nm/RIU, respectively. Temperature sensitivities of 3.5 and 9.8 pm/°C were also achieved for the envelope and fine fringes, respectively. The crosstalk between the RI and temperature was thus eliminated. In addition, the proposed sensor has a compact size, simple fabrication, and an all-fiber structure, making it a potential candidate for many applications, such as the food industry and environment monitoring.

Background Sub-chronic exposure to morphine can increase the potency of propofol but decrease the potency of ketamine by unknown mechanisms. The present study was designed to investigate the effects of sub-chronic exposure to morphine on the expression of neurotransmitter receptor subunits, which might contribute to the potency changes of ketamine and propofol in vivo. Methods Sub-chronic exposure to morphine was established by administering subcutaneous injections of morphine for 5 consecutive days. The median effective dose (ED50) of ketamine and/or propofol was measured on day 1, day 3, day 7 and day 15, after the last morphine dosage. Mice in the sham group received an equal volume of normal saline. The expressions of N-methyl D-aspartate (NMDA) receptor and γ-aminobutyric acid A (GABAA) receptor subunits in the forebrain were measured. Knockdown or overexpression of a subunit was used to determine the causality between the change in anesthetic potency and the expression of an identified receptor subunit. Results After sub-chronic exposure of mice to morphine, the expression of NMDA receptor 1 (NR1) was most elevated in the forebrain on day 1 (P Conclusions Sub-chronic exposure to morphine can differentially modulate the expressions of NR1 and GABAARβ3 in mice, which may contribute to the changes in ED50 of ketamine and propofol in vivo.

Coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has become a global pandemic worldwide. Long non‐coding RNAs (lncRNAs) are a subclass of endogenous, non‐protein‐coding RNA, which lacks an open reading frame and is more than 200 nucleotides in length. However, the functions for lncRNAs in COVID‐19 have not been unravelled. The present study aimed at identifying the related lncRNAs based on RNA sequencing of peripheral blood mononuclear cells from patients with SARS‐CoV‐2 infection as well as health individuals. Overall, 17 severe, 12 non‐severe patients and 10 healthy controls were enrolled in this study. Firstly, we reported some altered lncRNAs between severe, non‐severe COVID‐19 patients and healthy controls. Next, we developed a 7‐lncRNA panel with a good differential ability between severe and non‐severe COVID‐19 patients using least absolute shrinkage and selection operator regression. Finally, we observed that COVID‐19 is a heterogeneous disease among which severe COVID‐19 patients have two subtypes with similar risk score and immune score based on lncRNA panel using iCluster algorithm. As the roles of lncRNAs in COVID‐19 have not yet been fully identified and understood, our analysis should provide valuable resource and information for the future studies.

Ultrashort pulsed laser is a promising tool for processing transparent materials. We report on a new approach that simultaneously creates a pair of conjugate grooves on the bottom surface of a thin glass substrate at the duration of plowing a V-shaped microgroove on the top surface using the technique of direct laser ablation. We propose a hypothesis to explain the accompanying grooves’ formation mechanism and simulate Maxwell’s equations to verify its applicability. Measurements showed the surface roughness of the groove’s sidewalls was 0.14 $\mu \text{m}$ . This method requires no mask, can be directly performed in the atmosphere, and can simultaneously produce microgrooves on both sides of the substrate that render it an effective approach for producing high quality V-shaped microgrooves on both sides of the substrate.

BACKGROUND: Pediatric mitral regurgitation (MR), especially with bileaflet prolapse, is relatively rare, of high complexity, and frequently associated with other congenital cardiac abnormalities. It remains a major therapeutic challenge for surgeons. This study reports our experience of surgical treatment of this mitral disease and midterm follow-up results. METHODS: Between January 2016 and April 2020, nine pediatric patients, six females and three males, age ranged from 3 to 12 years (median age was 6 years) with a weight range of 12-36 kg (median weight was 25 kg), who all had over moderate regurgitation caused by bileaflet prolapse with mean distance of leaflet coaptation beyond annular plane 5.89 ± 1.66 mm (4-9 mm), received mitral valve (MV) repair. Various surgical techniques were used to repair MV. RESULTS: The median follow-up period was 23(6-51) months, only one patient had moderately severe recurrent of MR, no patient developed systolic anterior motion (SAM) or mitral stenosis. Freedom from reoperation was 100% during the follow-up period. Compared to preoperation, the left atrial (LA) diameter and left ventricular end-diastolic diameter (LVEDD) decreased significantly from 2.94 ± 0.49 cm to 2.37 ± 0.38 cm (LA, p < .01) and from 4.13 ± 0.73 cm to 3.62 ± 0.49 cm (LVEDD, p < .01) respectively, ejection fraction (EF) decreased significantly (p < .05) from 68.56 ± 3.98% to 62.89 ± 4.48% before discharged. CONCLUSION: We share our experience of surgical repair of mitral valve bileaflet prolapse in pediatric patients. Several surgical methods are considered to be used to repair the MV due to the high complexity of lesions. Anatomic correction or functional correction in our reports almost reaches the same result, while functional correction means simpler operation.

Sarcomatoid malignant mesothelioma (SMM) tends to occur in the pleura and is morphologically similar to lung sarcomatoid carcinoma (LSC) and organizing pleuritis (OP). Because SMM often does not express mesothelial markers, it is very difficult to distinguish from LSC and OP. GATA-binding protein 3 (GATA3) is a specific immunohistochemical (IHC) marker of breast and urothelial carcinoma. We routinely find that GATA is expressed in MM; however, GATA3 expression in SMM and its reference value for distinguishing SMM from LSC and OP remain unclear. Here, we used IHC methods to detect the expression of GATA3 and classic mesothelial markers in 17 SMM, 12 LSC, and 7 OP cases. We detected the following expression rates in SMM versus LSC cases: GATA3 (70.6% vs. 16.7%, p = 0.008), calretinin (52.9% vs. 8.3%, p = 0.019), Wilms tumor (WT)-1 (64.7% vs. 0%, p = 0.000), D2-40 (47.1% vs. 16.7%, p = 0.126), CK5/6 (35.3% vs. 25.0%, p = 0.694), and pan-cytokeratin (CKpan) (88.2% vs. 100.0%, p = 0.498). The specificities of calretinin, WT-1, and GATA3 in distinguishing SMM from LSC were 91.7%, 100%, and 83.3%, respectively, and combinations of any two of these three markers exhibited 100% specificity for SMM. Notably, the sensitivity of calretinin+/WT1+ staining for SMM was only 23.5%, which increased to 64.7% after including GATA3. Furthermore, all OP cases showed partial or diffuse expression of CKpan, WT-1, and D2-40 but no GATA3 and calretinin expression. In conclusion, GATA3 is an IHC marker with excellent sensitivity and specificity for SMM, and the combined consideration of GATA3, calretinin, and WT-1 was best for distinguishing SMM from LSC. Moreover, CKpan, WT-1, and D2-40 had no value for distinguishing SMM from OP, and GATA3 and calretinin were the most specific markers for distinguishing these two lesions.

It is crucial to maintain the balance of economic development and ecosystem protection. The value of ecosystem services is an indicator to help people understand the importance of ecosystem protection. Traditional models estimate ecosystem service values only according to land use/cover data while ignoring vegetation status differences in the same land use/cover. This study uses the normalized difference vegetation index (NDVI), the leaf area index (LAI), and net primary productivity (NPP) as vegetation status data to describe the differences in the same land use/cover type. The principal component analysis (PCA) approach is used to reduce the correlations among the three types of vegetation status data. Then, the calculated vegetation status index after PCA is input into the estimation model. The case study in China shows that the improved model has two major advantages. First, it can clearly distinguish the differences in ecosystem service values even for the same land use/cover type. Second, it can clearly describe the transitional zones between different land use/cover types through continuous changes in ecosystem service values. This improved model can provide a more detailed description of the distribution characteristics of ecosystem service values in China and help policymakers balance economic development and ecosystem protection.

Brain necrosis (RN) is a common radiotherapy sequela for brain metastases. Bevacizumab is identified as a therapeutic strategy for RN. This study aimed to study the clinical and radiobiological impacts on the efficacy of Bevacizumab in treating RN following stereotactic radiosurgery (SRS) for brain metastases.From April 2011 to November 2019, 40 patients diagnosed with RN after SRS for brain metastases were retrospectively analyzed. Patients were treated with Bevacizumab for RN and follow-up for 6 months using MR imaging at different timepoints. Linear regression was performed to evaluate the relationship between these variables.The median time course from the end of radiotherapy to the onset of RN was 11 months (range, 7-35 months). No significant difference was found in the edema volume between the chemotherapy group and non-chemotherapy group (P0.05). Patients received with SRS + WBRT exhibited relatively larger edema volumes post radiotherapy than those without WBRT (P0.05). Interestingly, the ratio of BED/GTV (Gy/cm3 ) correlated positively with the severity (time for half-reduction dose of corticosteroids) (r2 =0.13, P0.05), and negatively with the latency period (time course for development of radiation-induced brain necrosis) (r2 =0.21, P0.01). A new radiation doses volume index, BED × GTV (Gy·cm3 ), was proposed to facilitate the risk stratifications of patients for radiation-induced brain necrosis. Furthermore, no significant difference was found in alleviating brain edema between different regimens of Bevacizumab, i.e., 5 vs. 10 mg/kg, 2 vs.2 cycles (both P0.05).Bevacizumab is a feasible and favorable salvage treatment of BN after SRS for patients with BM. The efficacy is mainly manifested in radiological improvement and symptoms alleviation. The development of RN was found to be largely associated with radiation dose and gross tumor volume, and thus we proposed two new indexes, i.e., BED/GTV (Gy/cm3 ) for quantitative assessment of the severity and latency time, and BED × GTV (Gy·cm3 ) for risk stratifications for BN. A low dose with two cycles of Bevacizumab is recommended.

Two-dimensional all-inorganic halide perovskites (CsPbX3, X = Cl, Br or I) have emerged as prominent materials due to their unique properties, including ultrathin thickness in high surface area for catalysis, good mechanical flexibility for flexible electronics/optoelectronics, and high charge extraction and transport for photodetectors. However, the high luminescence of two-dimensional Mn-doped CsPbX3 that is crucial to light-emitting diodes and display applications remains unfulfilled. The existing synthesis approaches of two-dimensional Mn-doped CsPbX3 usually result in low luminescence because of either low solubility of precursors at low temperature or high concentrated nanocubes at high temperature (e.g. 180 °C). Herein, we report a moderate-temperature and atmospheric approach to synthesize highly luminescent Mn-doped CsPbCl3 nanoplatelets with only 4 monolayers. Different Mn–Pb feed ratios are explored to study the morphology evolution from nanocubes to nanoplatelets and the corresponding influence of two emission peaks at around 400 nm and 600 nm. The photoluminescence quantum yield (PLQY) of our Mn-doped CsPbCl3 nanoplatelets is up to 53.76%, which is the highest reported value in Mn-doped two-dimensional all-inorganic halide perovskites. The nanoplatelets exhibit excellent stability at room temperature in air (over 60 days). For the first time, both orange-red and warm white light-emitting diodes (LEDs) have been achieved through the nanoplatelets as the color conversion materials. Moreover, flexible composite fluorescent polymer films based on the nanoplatelets are demonstrated with high luminescence and stability (over 6 months), which indicate prominent potential in flexible displays.

Accurate fire load (combustible objects) information is crucial for safety design and resilience assessment of buildings. Traditional fire load acquisition methods, such as fire load survey, which are time-consuming, tedious, and error-prone, failed to adapt to dynamic changed indoor scenes. As a starting point of automatic fire load estimation, fast recognition and detection of indoor fire load are important. Thus, this research proposes a computer vision-based method to automatically detect indoor fire loads using deep learning-based instance segmentation. First, indoor elements are classified into different categories according to their material composition. Next, an image dataset of indoor scenes with instance annotations is developed. Finally, a deep learning model, based on Mask R-CNN, is developed and trained using transfer learning to detect fire loads in images. Experimental results show that our model achieves promising accuracy, as measured by an average precision (AP) of 40.5% and AP50 of 59.2%, for instance segmentation on the dataset. A comparison with manual detection demonstrates the method’s high efficiency as it can detect fire load 1200 times faster than humans. This research contributes to the body of knowledge 1) a novel method of high accuracy and efficiency for automated fire load recognition in indoor environments based on instance segmentation; 2) training techniques for a deep learning model in a relatively small dataset of indoor images which includes complex scenes and a variety of instances; and 3) an image dataset with annotations of indoor fire loads. Although instance segmentation has been applied for several years, this is a pioneering research on using it for automated indoor fire load recognition, which paves the foundation for automatic fire load estimation and resilience assessment for the built environment.

General anesthetics are a class of drugs that target the central nervous system and are widely used for various medical procedures. General anesthetics produce many behavioral changes required for clinical intervention, including amnesia, hypnosis, analgesia, and immobility; while they may also induce side effects like respiration and cardiovascular depressions. Understanding the mechanism of general anesthesia is essential for the development of selective general anesthetics which can preserve wanted pharmacological actions and exclude the side effects and underlying neural toxicities. However, the exact mechanism of how general anesthetics work is still elusive. Various molecular targets have been identified as specific targets for general anesthetics. Among these molecular targets, ion channels are the most principal category, including ligand-gated ionotropic receptors like γ-aminobutyric acid, glutamate and acetylcholine receptors, voltage-gated ion channels like voltage-gated sodium channel, calcium channel and potassium channels, and some second massager coupled channels. For neural functions of the central nervous system, synaptic transmission is the main procedure for which information is transmitted between neurons through brain regions, and intact synaptic function is fundamentally important for almost all the nervous functions, including consciousness, memory, and cognition. Therefore, it is important to understand the effects of general anesthetics on synaptic transmission via modulations of specific ion channels and relevant molecular targets, which can lead to the development of safer general anesthetics with selective actions. The present review will summarize the effects of various general anesthetics on synaptic transmissions and plasticity.

BACKGROUND Spontaneous bladder rupture is relatively rare, and common causes of spontaneous bladder rupture include bladder diverticulum, neurogenic bladder dysfunction, gonorrhea infection, pelvic radiotherapy, etc. Urinary bladder perforation caused by urinary catheterization mostly occurs during the intubation process. CASE SUMMARY Here, we describe an 83-year-old male who was admitted with 26 h of middle and upper abdominal pain and a history of long-term catheterization. Physical examination and computed tomography of the abdomen supported the diagnosis of diffuse peritonitis, most likely from a perforated digestive tract organ. Laparoscopic exploration revealed a possible digestive tract perforation. Finally, a perforation of approximately 5 mm in diameter was found in the bladder wall during laparotomy. After reviewing the patient’s previous medical records, we found that 1 year prior the patient underwent an ultrasound examination showing that the end of the catheter was embedded into the mucosal layer of the bladder. Therefore, the bladder perforation in this patient may have been caused by the chronic compression of the urinary catheter against the bladder wall. CONCLUSION For patients with long-term indwelling catheters, there is a possibility of bladder perforation, which needs to be dealt with quickly.

The study focuses on the integration of dynamic mathematics software (DMS) and cooperative learning into the teaching and learning process of inversely proportional functions. The aim of the study is to investigate the effects of integrating DMS with cooperative learning on students’ mathematics achievement using quasi-experimental research design. Students in treatment group learnt inverse proportional functions in cooperative learning groups with DMS while those in control group had typical approach of instruction. Participants are all ninth-grade students in a Macau private school. They were given an achievement test at three stages, namely as pre-test, post-test and delayed post-test. Analysis of students’ results showed that the pedagogy of cooperative learning with DMS does have significant influence on students’ mathematics achievement.

Rationale: Capillaries are composed of endothelial cells and the surrounding mural cells, pericytes. Microvascular repair after injury involves not only the proliferation of endothelial cells but also pericyte-based vessel stabilization. Exogenous bone marrow derived-putative endothelial progenitor cells (b-pEPCs) have the potential for vascular repair; however, their effect on vascular structure stabilization and pericyte-related pathobiological outcomes in the injured kidney has not been fully examined. Methods: We applied ischemia-reperfusion (IR) to induce renal vascular injury and renal fibrosis in mice. Platelet-derived growth factor receptor β (PDGFR-β)-DTR-positive mice were generated to deplete pericytes, and exogenous b-pEPCs and the PDGFR-β ligand, PDGF chain B (PDGF-BB), were employed to explore the relationship among b-pEPCs, pericytes, vascular repair, and early renal fibrosis. Results: Administration of b-pEPCs reduced IR-induced pericyte-endothelial detachment, pericyte proliferation, and myofibroblast transition via a paracrine mode, which preserved not only vascular stabilization but also ameliorated IR-initiated renal fibrosis. PDGF-BB upregulated the expression of PDGFR-β, exacerbated vascular abnormality, and pericyte-myofibroblast transition, which were ameliorated by b-pEPCs administration. The exogenous b-pEPCs and their culture medium (CM) induced vascular injury protection, and renal fibrosis was blocked by selective deletion of pericytes. Conclusion: Exogenous b-pEPCs directly protect against IR-induced vascular injury and prevent renal fibrosis by inhibiting the activation of PDGFR-β-positive pericytes.

Object. In this study, our aim is to evaluate the efficiency of extracorporeal shockwave therapy (ESWT) on chronic Achilles tendinopathy (CAT) with different courses of disease. Methods. The data of 66 patients with CAT received ESWT was reviewed. According to the disease courses, those cases were allocated to short-term group (ST group, symptom duration 3-6 months) and long-term group (LT group, symptom duration >6 months). Propensity scores match (PSM) method was conducted to eliminate the confound factors in baseline features including gender, sport history, sides, type of CAT, BMI (body mass index), age, and scores evaluated by AOFAS (American Orthopedic Foot and Ankle Society) and VAS (Visual Analogue Scale) before ESWT. After balancing the features between ST and LT group, postinterventional VAS, AOFAS, and rate of Likert satisfaction scale at the 3rd month after first ESWT was statistically analyzed. Results. Among the baseline features in ST and LT group, gender (female ratio, 44.4% vs 71.4%, p=0.041) and BMI (23.26±2.15 vs 24.63±2.41, p=0.024) were identified as confound factors. After elimination of biased features with PSM, 3 months after first ESWT, AOFAS and VAS in both groups are significantly improved, when compared with their scores at baseline (p<0.01). Moreover, at postintervention month 3 (PIM3), AOFAS in ST group is significantly higher than LT group (85.08±9.83 vs 76.76±9.85, t=76.76±9.85, p=0.019), and the rate of Likert satisfaction in ST group is better than LT group; although, it did not reach but close to significant level (70.6% vs 47.1%, χ2=1.943, p=0.163). However, there is no statistical difference of VAS scores between two groups after ESWT (1.96±0.98 vs 2.24±1.29, t=0.703, p=0.487). Conclusions. ESWT could effectively relieve pain and improve function of hind foot in patients with chronic Achilles tendinopathy, and especially, it could offer better benefit on functional improvement in patients with short duration of CAT symptom.

Background Volatile anesthetics moderately depress respiratory function at clinically relevant concentrations. Phox2b-expressing chemosensitive neurons in the retrotrapezoid nucleus, a respiratory control center, are activated by isoflurane, but the underlying mechanisms remain unclear. The hypothesis of this study was that the sodium leak channel contributes to the volatile anesthetics-induced modulation of retrotrapezoid nucleus neurons and to respiratory output. Methods The contribution of sodium leak channels to isoflurane-, sevoflurane-, and propofol-evoked activity of Phox2b-expressing retrotrapezoid nucleus neurons and respiratory output were evaluated in wild-type and genetically modified mice lacking sodium leak channels (both sexes). Patch-clamp recordings were performed in acute brain slices. Whole-body plethysmography was used to measure the respiratory activity. Results Isoflurane at 0.42 to 0.50 mM (~1.5 minimum alveolar concentration) increased the sodium leak channel–mediated holding currents and conductance from −75.0 ± 12.9 to −130.1 ± 34.9 pA (mean ± SD, P = 0.002, n = 6) and 1.8 ± 0.5 to 3.6 ± 1.0 nS (P = 0.001, n = 6), respectively. At these concentrations, isoflurane increased activity of Phox2b-expressing retrotrapezoid nucleus neurons from 1.1 ± 0.2 to 2.8 ± 0.2 Hz (P < 0.001, n = 5), which was eliminated by bath application of gadolinium or genetic silencing of sodium leak channel. Genetic silencing of sodium leak channel in the retrotrapezoid nucleus resulted in a diminished ventilatory response to carbon dioxide in mice under control conditions and during isoflurane anesthesia. Sevoflurane produced an effect comparable to that of isoflurane, whereas propofol did not activate sodium leak channel–mediated holding conductance. Conclusions Isoflurane and sevoflurane increase neuronal excitability of chemosensitive retrotrapezoid nucleus neurons partly by enhancing sodium leak channel conductance. Sodium leak channel expression in the retrotrapezoid nucleus is required for the ventilatory response to carbon dioxide during anesthesia by isoflurane and sevoflurane, thus identifying sodium leak channel as a requisite determinant of respiratory output during anesthesia of volatile anesthetics. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Currently, phosphor-converted LEDs (pc-LEDs) are revolutionizing the industry of plant growth lighting. To meet the requirements of this technology, phosphors with tunable photoluminescence, high thermal stability and luminous intensity are required. Herein, we found that the simple substitution of yttrium for lanthanum in La2MgTiO6:Mn4+ (LMT:Mn4+) system could satisfy above three criteria simultaneously. The photoluminescence properties can be regulated by continuously controlling the chemical composition of La2-xYxMgTiO6:Mn4+ solid solution. The La sites are occupied by Y ions, causing a significant blue shift in the emission spectra which owing to the change of local crystal field strengthen. Meanwhile, the thermal stability and decay lifetimes are also varied due to the variation of local structure and band gap energy. The thermal stability of the material reaches 83.5% at 150 °C, which is better than the reported La2MgTiO6:Mn4+ and Y2MgTiO6:Mn4+ phosphors. The electronic luminescence (EL) of pc-LED devices using La2-xYxMgTiO6:Mn4+ red phosphor is evaluated, which matching the absorption regions of plant pigments well, reflecting the superiority of the studied phosphors in plant growth lighting areas.

BACKGROUND Motor disturbances in Parkinson's disease (PD) mainly result from the degeneration of classic motor pathways. Given that the specific limbic pathway participates in movements, it is reasonable to consider that limbic pathway have the pathologic potential of motor disturbance in PD. PURPOSE To explore the white matter changes of limbic and motor pathways and their relations in PD patients. STUDY TYPE Prospective. POPULATION 39 PD patients and 55 normal controls. SEQUENCE Sagittal 3D T1 -weighted fast spoiled gradient recalled sequence, diffusion-weighted spin echo-echo planar imaging sequence on a 3T scanner. ASSESSMENT Probabilistic tractography was used to reconstruct the motor pathways (nigrostriatal-nigropallidal and basal ganglia-motor cortex pathways) and limbic pathway (amygdala-accumbens-pallidum pathway). White matter alterations of these pathways were evaluated by fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), neurite density (NDI), and orientation dispersion (ODI). Clinical assessment was conducted by a neurologist. STATISTICAL TESTS Group comparisons were performed using unpaired t-tests. Pearson or Spearman correlation was used to explore the relationships between variables. RESULTS Compared with normal controls, PD patients showed decreased ODI as well as increased MD and AD in the bilateral nigrostriatal-nigropallidal pathway (P

The studies comparing laparoscopic spleen-preserving distal pancreatectomy (LSPDP) and laparoscopic distal pancreatosplenectomy (LDPS) are limited. This study aimed to compare clinical outcomes and quality of life of patients undergoing LSPDP and LDPS. Between March 2004 and December 2014, patients who underwent laparoscopic distal pancreatectomy were reviewed. Patients were divided into 2 groups as LSPDP and LDPS. Data considered for comparison analysis were patient demographics, intraoperative variables, morbidity, postoperative hospital stay, mortality, pathologic findings, and quality of life (SF-36 questionnaire). A total of 110 patients (50 LSPDP and 60 LDPS) were included in the final analysis. Baseline characteristics were similar in the 2 groups. The LSPDP group had a significantly shorter operative time(153.3 ± 46.2 vs. 179.9 ± 54.1 min, p = 0.015) than the LDPS group. Also in analysis of propensity-matched population(LSPDP:LDPS = 35:35, 1:1 matching), LSPDP group still had a significantly shorter operative time (159.3 ± 36.2 vs. 172.9 ± 44.1 min, p = 0.045) than the LDPS group.There were no significant differences with respect to estimated blood loss, first flatus time, diet start time, and postoperative hospital stay. Postoperative outcomes, including morbidity, pancreatic fistula rates, and mortality, were similar in the LSPDP and LDPS group. On the follow-up survey, the total quality of life score (635.8 ± 50.7 vs. 596.1 ± 92.1)was higher in the LSPDP group compared with the LDPS group. However, the differences were not statistically significant(p > 0.05). The score in vitality (82.5 ± 14.4 vs. 68.9 ± 11.4, p = 0.046) was significantly higher in LSPDP group and not statistically significant in other areas (p > 0.05).Similar results of quality of life assessment were found in analysis of propensity-matched population. Compared to LDPS, LSPDP had shorter operating time and better quality of life with similar morbidity and recovery period.

Purpose At present, there are few studies on the mechanisms underlying postoperative recurrence of liver cancer, and the mechanism of action of miR-602 in postoperative recurrence of liver tumors is not clear. Our goals were to investigate the effects of miR-602 on the expression of the Ras-associated domain family 1A (RASSF1A) gene and the regulation of primary and recurrent hepatic tumors to clarify the molecular mechanisms of miR-602 in postoperative hepatocellular carcinoma. Methods We constructed a mouse liver orthotopic tumor model and a mouse liver recurrent tumor model. We measured the expression levels of the RASSF1A gene and then analyzed the effects of miR-602 on the regulation of RASSF1A. We transiently transfected the miR-602 gene into cells that stably overexpressed RASSF1A and examined relevant indicators to elucidate the mechanisms by which miR-602 regulates the RASSF1A/c-Jun N-terminal kinase (JNK) pathway in recurrence and dormancy in liver cancer. Results RASSF1A expression was inversely related to that of JNK, activating transcription factor 2 (ATF-2), and c-Jun in SMMC7721 cells stably transfected with the RASSF1A gene and in recurrent mouse tumor tissues. After transient transfection of cells with miR-602 mimic or miR-602 inhibitor, the expression of miR-602 was inversely related to that of RASSF1A. Conclusion MiR-602 might inhibit the JNK signaling pathway by inhibiting the expression of RASSF1A, thereby promoting recurrence of liver cancer after surgery. The low expression levels of miR-602 in liver cancer tissues were closely related to postoperative recurrence; they could be used as a marker to judge the prognosis of patients with liver cancer.

Parkinson's disease (PD) is characterized by complex clinical symptoms, including classic motor and nonmotor disturbances. Patients with PD vary in clinical manifestations and prognosis, which point to the existence of subtypes. This study aimed to find the fiber connectivity correlations with several crucial clinical symptoms and identify PD subtypes using unsupervised clustering analysis. One hundred and thirty‐four PD patients and 77 normal controls were enrolled. Canonical correlation analysis (CCA) was performed to define the clinically relevant connectivity features, which were then used in the hierarchical clustering analysis to identify the distinct subtypes of PD patients. Multimodal neuroimaging analyses were further used to explore the neurophysiological basis of these subtypes. The methodology was validated in an independent data set. CCA revealed two significant clinically relevant patterns (motor‐related pattern and depression‐related pattern; r = .94, p, Parkinson's disease (PD) is a heterogeneous syndrome, which points to the subtypes in PD patients. This study used a data‐driven approach based on fiber connectivity to automatically identify subtypes in PD patients with distinct clinical features. Neuroimaging analyses revealed significant brain alterations behind each subtype.

OBJECTIVES To evaluate the surrounding tissue stiffness measured by sound touch elastography for differential diagnosis of thyroid nodules (TNs). METHODS Thirty-nine benign and 90 malignant TNs were included in this study. The conventional ultrasound features, the maximum Young modulus value of the stiffness of the TNs (recorded as E), and the stiffness of the 0.5-, 1.0-, 1.5-, and 2.0-mm perinodular regions of the TNs (recorded as Eshell0.5 , Eshell1.0 , Eshell1.5 , and Eshell2.0 , respectively) were prospectively analyzed and compared to histopathologic results. The abundance of collagen fibers at various widths in the perinodular regions of the TNs was evaluated by Masson staining and ImageJ software (National Institutes of Health, Bethesda, MD). The fibrous structures in the perinodular regions of the TNs were classified. RESULTS The various Eshell values of malignant TNs were significantly higher than those of benign TNs (P

Development of high-performance ammonia (NH3) sensor is imperative for monitoring NH3 in the living environment. In this work, to obtain a high performance NH3 gas sensor, structurally well-defined WO3@SnO2 core shell nanosheets with a controllable thickness of SnO2 shell layer have been employed as sensing materials. The prepared core shell nanosheets were used to obtain a miniaturized gas sensor based on micro-electro-mechanical system (MEMS). By tuning the thickness of SnO2 layer via atomic layer deposition, a series of WO3@SnO2 core-shell nanosheets with tunable sensing properties were realized. Particularly, the sensor base on the fabricated WO3@SnO2 nanosheets with 20-nm SnO2 shell layer demonstrated superior gas sensing performance with the highest response (1.55) and selectivity toward 15 ppm NH3 at 200 °C. This remarkable enhancement of NH3 sensing ability could be ascribed to the formation of unique WO3-SnO2 core-shell heterojunction structure. The detailed mechanism was elucidated by the heterojunction-depletion model with the help of specific band alignment.

Background and objectiveLong-acting nociceptive-selective regional anesthesia has remained an elusive clinical goal. We aspired to identify a novel compound that would produce nociceptive-selective regional anesthesia through the transient receptor potential vanilloid 1 (TRPV1) channels.MethodsWe designed and synthesized a novel compound (LL-a) that penetrates the cell membrane through TRPV1 channels and binds to voltage-gated sodium channels. The regional anesthetic effect of LL-a was evaluated in a rodent sciatic nerve block model. Electrophysiological recording was applied to test the inhibition of LL-a on voltage-gated sodium channel currents.ResultsLL-a inhibited sodium channel currents on the dorsal root ganglion neurons of mice and this action was diminished by TRPV1 channel knockout. In a sciatic nerve block model of a rat, 0.2% and 0.4% (w/v) LL-a produced selective sensory block with median (IQR) durations of 42.0 (24.0, 48.0) and 72.0 (69.0, 78.0) hours, respectively. No motor block was found for 0.2% LL-a. 0.4% LL-a produced a motor block with a median (IQR) duration of 3.0 (0.0, 6.0) hours. This selective sensory block was not observed on TRPV1 knockout mice. As a positive control, 0.5% and 0.75% levobupivacaine produced a non-selective sciatic nerve block with median (IQR) durations of 2.8 (2.6, 2.8) and 3.8 (3.8, 4.8) hours, respectively. No systemic or local irritation was observed during injection of LL-a and sensory and motor function completely recovered for all the animals.ConclusionsLL-a is a potential novel local anesthetic for long-lasting nociceptive-selective analgesia.

Flexible pressure sensing is required for the excellent sensing performance and dexterous manipulation of the measured objects in their potential applications. Particularly, the ability to measure and discriminate the direction of force, contact surface, and contact location in real time is crucial for robotics with tactile feedback. Herein, a three-dimensional elastic porous carbon nanotube (CNT) sponge is synthesized by chemical vapor deposition, which is successfully applied in the piezoresistive sensor. In situ scanning electron microscopy study intuitively illustrates the characteristics that the microfibers of the CNT sponge distort and contact with each other under an external force. As a result, new conductive paths are created at the contact points between the CNT microfibers, which provides a basic sensing principle for a piezoresistive sensor. The CNT sponge-based sensor has an ultrahigh sensitivity in a wide pressure range (0-4 kPa for 4015.8 kPa-1), a rapid response time of 120 ms, and excellent durability over 5000 cycles. Moreover, a finlike flexible double-sided electronic skin (e-skin) is fabricated by a simple method to achieve force direction detection, which has potential applications in intelligent wearable devices and human-machine interaction.

We demonstrate a synchronously self-Q-switched and self-mode-locked output pulse fiber laser based on a linear compound resonator and an LD cladding-pumped Yb-doped double-clad fiber. A maximum average output power of 332.1 mW is achieved. We observe that the maximum pulse envelope width is 8 μs, and the pulse energy is 3.83 μJ for the self-Q-switched pulse envelope. At the same time, the achieved maximum pulse width is 37.8 ns and pulse energy is 17.61 nJ for the self-mode-locked pulse. We observe the pulse splitting of the self-Q-switched envelope as well and achieve 14 subpulse packets for L1 = 180 mm. There are 75 self-mode-locked pulses in single packets.

Inborn errors of metabolism (IEMs) can cause intellectual disability or even death in children. To evaluate the disease spectrum and genetic characteristics of IEMs in Jining City of Shandong Province in East China, we used tandem mass spectrometry (MS/MS) technology for IEMs screening combined with genetic analysis. Newborns were screened from July 14, 2014, to December 31, 2018. Amino acid and carnitine contents were detected by MS/MS. According to the results for normal newborns, the reference range of our laboratory was established with the percentile method. The suspected positive newborns were further diagnosed using next-generation sequencing. A total of 514,234 newborns were screened, and 265 were diagnosed with IEMs, with a detection rate of 1:1941. Of the 265 patients, 130 (49.06%) had organic acid disorders, 83 (31.32%) had amino acid disorders, 34 (12.83%) had fatty acid oxidation disorders, and 18 (6.79%) had urea circulatory disorders. PAHD and MMA were the two most common disorders. IEMs-associated genes were identified in 233 patients. Our data indicated that IEMs are never uncommon in Jining, and the disease spectrum and genetic background were clearly elucidated, contributing to the treatment and prenatal genetic counseling of these disorders in the region.

Summary: Objective: This study evaluates growth of pulmonary artery (PA) between different age groups after Modified Blalock-Taussig shunt (MBTS) based on a single center experience. Methods: We retrospective analyzed outcomes of 90 patients undergoing MBTS in our institute from January 1, 2010 to May 1, 2018. Patients were divided into three groups: Group 1, ≦2 months, Group 2, >2 months, ≦24 wmonths, Group 3, >24 months. The outcome included PA growth, overall survival rates and postoperative complications. Results: 23 patients were involved in Group 1, while 49 in Group 2 and 18 in Group 3. The diameter of the PA, McGoon ratio, Nakata index and the oxygen saturation increased significantly after MBTS. Compared to pre-MBTS, there was no statistically significant increase of McGoon ratio in Group 3 after performing MBTS, but it witnessed less secondary cardiac surgery rate compared with Group 2 (11.11% vs. 48.98%, P = 0.005). Cumulative survival rates of three groups were 60.53%, 85.70%, 94.40% at 1 year; 60.53%, 78.30%, 87.75% at 3 years and 60.53%, 78.30%, 87.75% at 5 years. Multivariable analysis showed diastolic blood pressure

Background Mixed evidence challenges preoperative alpha-fetoprotein (AFP) as an independent prognostic factor for patients with hepatocellular carcinoma (HCC) after hepatectomy. Results Daily post-operative decrease of AFP by 9% as compared to the preoperative level (A09) were selected as the Cut-off. The Kaplan-Meier curve showed that A09 was significantly different for OS (P=0.043) and RFS (P=0.03). A decrease in risk by 54% was observed for OS and 32% for RFS in the at-risk population (A09>9%). A better concordance was observed after adding A09 into TNM and BCLC staging systems. Moreover, a consistent concordance was observed in the internal (FDZS5:0.63; FDZS3:0.608) and external (FDZS5:0.85; FDZS3:0.762) validation cohorts, suggesting its prognostic value in HCC population with elevated AFP. Conclusions Decrease in perioperative serum AFP rather than preoperative AFP is an independent prognostic factor for HCC patients after hepatectomy. Cut-off A09 significantly discriminates overall and recurrence-free survival and could be interpret into TNM and BCLC staging systems to improve the stratification power for HCC patients with elevated AFP. Methods Kaplan-Meier curve depicted the differences of overall survival (OS) and recurrence-free survival (RFS). Nomogram and concordance were employed to evaluate the superiority of the current staging system.