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Intestinal electrical stimulation (IES) has been proposed for treating diabetes; however, its parameters need to be further systematically optimized. This study aimed to optimize the parameters of IES and investigate its possible mechanisms involving glucagon-like peptide-1 (GLP-1) in diabetic rats.Thirty-six high-fat diet-induced diabetic rats were chronically implanted with a pair of bipolar electrodes at the duodenum for IES. The oral glucose tolerance test (OGTT) was performed in a number of sessions with IES using different parameters and biphasic charge-balanced waveforms to derive the best values for train on-time, pulse frequency, and pulse width. Incretin hormones such as GLP-1 were assessed and the GLP-1 antagonist Exendin 9-39 was used to assess the role of GLP-1 in the ameliorating effect of IES on hyperglycemia.The most effective IES parameters in reducing blood glucose (BG) during the OGTT were derived: 1.2 sec on, 0.3 sec off, 80 Hz, 3 msec. IES with these parameters reduced BG level by at least 29% from 15 min to 180 min (p 0.05 for all points, N = 10). IES with these stimulation parameters increased plasma GLP-1 level at 30 min, 60 min, 90 min and gastric inhibitory peptide (GIP) level at 30 min (N = 8). Exendin 9-39 blocked the inhibitory effect of IES on BG (p 0.05, IES + Exendin 9-39 vs sham-IES, N = 8).IES with the most effective parameters derived in this study improves hyperglycemia in diabetic rats. The ameliorating effect of IES on hyperglycemia is attributed to the enhanced release of GLP-1. IES has great potential for treating diabetes.

This study aims to introduce a new sagittal cephalometric measurement, the sagittal G-triangle analysis, to accurately and reproducibly assess the sagittal jaw relationship. Sagittal G-triangle analysis, which consists of angles AXK and BXK, is based on an equilateral triangle (Bo-X-K) constructed using 5 cephalometric landmarks (Ba, Bo, Po, Or, and G). To test the diagnostic efficiency of this analysis, pretreatment cephalometric radiographs of 120 female and 120 male Chinese patients were randomly selected. For each enlisted subject, angles SNA and SNB as well as angles AXK and BXK were measured and recorded. On the basis of the SNA and SNB results, subjects were categorized into 6 groups: maxillary retrognathism, normal maxilla, maxillary prognathism, mandibular retrognathism, normal mandible, and mandibular prognathism. The diagnostic efficiency of angles AXK and BXK were evaluated using various statistical tests. A high correlation was detected between angles SNA and AXK as well as between angles SNB and BXK. Female patients with angle AXK between -2.255° and 2.860° and male patients with angle AXK between -2.615° and 2.120° were considered to have a normal maxilla position. Female patients with angle BXK between -2.61° and 2.93° and male patients with angle BXK between -2.275° and 0.610° were considered to have a normal mandible position. In conclusion, sagittal G-triangle analysis could be used as an alternative method for the evaluation of the sagittal position of the maxilla and mandible in cephalometric analysis.

Solar energy is the source of energy required for the dry methane reforming (DMR). In the high temperature field induced by concentrated solar energy, the spatial distribution of radiation intensity has a significant impact on the solar thermochemical performance. Based on principle of minimum Gibbs free energy (Gmin), the idea of regulating radiation field to match solar thermochemical energy conversion on-demand is proposed. To improve solar thermochemical conversion efficiency, biomimetic hierarchical porous structure is introduced as solar thermochemical reactor, which can optimize both the radiation field and temperature field. The analysis model of solar driven DRM is established, combined with user-defined functions (UDFs). The effects of pore diameter combinations along the direction of L and R on the reforming properties are studied. The results show that by designing biomimetic hierarchical porous structure, the temperature of solar thermochemical reactor can approach the thermodynamic temperature (1050 K), and finally the methane conversion is improved by up to 7%.

Objective To explore the applications of 3-dimensional digital subtraction angiography (3D-DSA) double-volume reconstruction technique (DVRT) in endovascular embolization for the treatment of intracranial aneurysm. Methods A cohort of 112 patients with a total of 127 intracranial aneurysms admitted to the neurosurgery department from June 2018 to October 2019 were selected. Cerebrovascular angiographies were performed after admission. Patients were divided into observation group (56 of 112) and control group (56 of 112) randomly when endovascular embolization was performed. Individuals in the control group were treated with 2D-DSA technique, and patients in the observation group were treated with 3D-DSA DVRT. The Raymond method was used to determine the degree of embolism. Results There was no significant difference in sex, blood pressure, cerebral atherosclerosis, aneurysm site or size, contrast agent dosage, x-ray dose, or surgical cost between the 2 groups. There was no postoperative recurrence in the observation group. However, the recurrence rate in the control group is 10.7% (6 of 56). Postoperative thrombosis occurred in 1 case (1 of 56, 1.8%) in the observation group and 7 cases (7 of 56, 12.5%) in the control group. No postoperative cerebral infarction was recorded in the observation group, while 5 cases (8.9%, 5 of 56) in the control group presented with postoperative cerebral infarction. Conclusions 3D-DVRT for intracranial aneurysm embolization provides the best working angle, clearly shows the process of aneurysm embolization and its relationship with peripheral vessels, and reduces the occurrence of surgical complications including postoperative recurrence, thrombosis, and cerebral infarction.

OBJECTIVES Constipation and opioid-induced constipation (OIC) are common with limited treatment options. We investigated whether a noninvasive method of auricular vagal nerve stimulation (aVNS) could be used for treating OIC and explored its potential mechanisms and neural pathways in a rodent model of OIC. MATERIALS AND METHODS Sprague-Dawley were chronically implanted with one pair of auricular electrodes for aVNS. Sixteen rats were treated with loperamide for a week while another 16 rats received bilateral vagotomy, then randomly treated with aVNS or sham-aVNS for a week. In addition, eight normal rats were implanted with a polyethylene catheter in the proximal colon for assessing whole colon transit. RESULTS 1) The number of fecal pellets and water content in feces increased after aVNS, compared with sham-aVNS. 2) aVNS accelerated colon transit and whole gut transit, compared with sham-aVNS. 3) In colon tissues, aVNS increased the protein expression of choline acetyltransferase, glial cell line-derived neurotrophic factor and the c-kit expression in myenteric interstitial cells of Cajal but decreased the protein expression of neural nitric oxide synthase (p

Background and objectives This study aimed to compare outcomes between neoadjuvant imatinib and upfront surgery in patients with localized rectal gastrointestinal stromal tumors (GIST) patients. Methods Eighty-five patients with localized rectal GIST were divided into two groups: upfront surgery ± adjuvant imatinib (Group A, n = 33) and the neoadjuvant imatinib + surgery + adjuvant imatinib (Group B, n = 52). Baseline characteristics between groups were controlled for with inverse probability of treatment weighting (IPTW) adjusted analysis. Results The response rate to neoadjuvant imatinib was 65.9%. After the IPTW-adjusted analysis, patients who underwent neoadjuvant therapy had better distant recurrence-free survival (DRFS) and disease-specific survival (DSS) compared with those who underwent upfront surgery (5-year DRFS 97.8 vs. 71.9%, hazard ratio [HR], 0.15; 95% CI, 0.03-0.87; p = 0.03; 5-year DSS 100 vs. 77.1%; HR, 0.11; 95% CI, 0.01-0.92; p = 0.04). While no significant association was found between overall survival (OS) and treatment groups (p = 0.07), 5-year OS was higher for the neoadjuvant group than upfront surgery group (97.8% vs. 71.9%; HR, 0.2; 95% CI, 0.03-1.15). Conclusions In patients with localized rectal GIST, neoadjuvant imatinib not only shrunk the tumor size but also decreased the risk of metastasis and tumor-related deaths when compared to upfront surgery and adjuvant imatinib alone.

Fast and accurate quantitative detection of 14CO2 has important applications in many fields. The optical detection method based on the sensitive cavity ring-down spectroscopy technology has great potential. But currently it has difficulties of insufficient sensitivity and susceptibility to absorption of other isotopes/impurity molecules. We propose a stepped double-resonance spectroscopy method to excite 14CO2 molecules to an intermediate vibrationally excited state, and use cavity ring-down spectroscopy to probe them. The two-photon process significantly improves the selectivity of detection. We derive the quantitative measurement capability of double-resonance absorption spectroscopy. The simulation results show that the double-resonance spectroscopy measurement is Doppler-free, thereby reducing the effect of other molecular absorption. It is expected that this method can achieve high-selectivity detection of 14CO2 at the sub-ppt level.

Background Minimal deviation adenocarcinoma is a rare malignancy with a high rate of misdiagnosis and high aggressiveness, and its diagnosis relies on histopathology. Surgical resection is the preferred and most effective treatment, but the outcomes are often unsatisfactory. Case summary A 60-year-old perimenopausal woman was admitted to the hospital and found to have elevated CA19-9 on physical examination without abdominal pain or vaginal bleeding. Clinical examination and positron emission tomography/computed tomography examination were unremarkable, magnetic resonance imaging examination was suggestive of dominant cervical lesions, and methylation examination was suggestive of malignant lesions. Tissue samples were taken from the suspected cervical lesion, and the final pathologic diagnosis was minimal deviation adenocarcinoma. Based on the pathologic diagnosis of suspected minimal deviation adenocarcinoma, radical abdominal total hysterectomy, bilateral oophorectomy, and pelvic and para-aortic lymph node dissection were performed. The final histological report confirmed minimal deviation adenocarcinoma of the cervix, stage IB2, with lymph node metastasis. Minimal deviation adenocarcinoma is a tumor with aggressive clinical behavior. Conclusion Patients with minimal deviation adenocarcinoma have a lower survival rate than patients with conventional human papillomavirus-related cervical adenocarcinoma. A precise preoperative pathologic diagnosis may reduce the mortality rate due to missed optimal treatment with multiple surgical interventions. To date, there is no therapeutic consensus; therefore, each case must be treated individually.

The vein hierarchical structure has high efficiency of component transportation capacity, it has been widely used in energy storage, solar thermochemical reactions, and photocatalysis. In this pape...

Marine structures are inevitably influenced by parametric perturbations as well as multiple external loadings. Among these loadings, earthquake is generally more destructive and unpredictable than others. It is significant to develop effective active control schemes to guarantee the safety, stability, and integrity of marine structures subject to earthquakes and parametric perturbations. In this paper, the problem of networked [Formula: see text] robust damping control is addressed to stabilize a marine structure subject to earthquakes. First, in consideration of perturbations of the structure parameters, an uncertain model of the networked marine structure under earthquakes is presented. Second, a robust networked [Formula: see text] control scheme is presented to suppress seismic responses of the structure. By using stability theory of time-delay systems, several sufficient conditions on robust stability of the networked marine structure system are obtained, and the linear matrix inequality methods are utilized to solve the gain matrix of the controller. Finally, simulation indicates that compared with the traditional robust [Formula: see text] control and the proposed networked [Formula: see text] control, the seismic responses amplitudes of the marine structure under the two controllers are almost the same, while the latter is more economic than the former.

Introduction Subcutaneous galcanezumab was an effective, well-tolerated preventive treatment for adults with episodic (EM) or chronic migraine (CM) in 4 phase 3 randomized controlled trials: EVOLVE-1, EVOLVE-2, REGAIN, and CONQUER. Number needed to treat (NNT) and to harm (NNH) are metrics of effect size used to evaluate benefit–risk profiles. This study evaluated NNT, NNH, and benefit–risk profiles (measured as likelihood to be helped or harmed, LHH) of galcanezumab 120 mg versus placebo in patients with EM or CM. Methods Primary efficacy outcomes were responses defined as ≥ 30%, ≥ 50%, and ≥ 75% reductions from baseline in number of monthly migraine headache days in patients with EM (EVOLVE-1; EVOLVE-2; CONQUER) and CM (REGAIN; CONQUER); corresponding NNTs to achieve respective responses; and corresponding NNHs for discontinuations due to adverse events (DCAEs) among the safety population. Secondary efficacy outcomes were responses for patients with ≥ 2 failed prior preventive treatments due to lack of efficacy and/or for tolerability reasons. All LHHs were based on ≥ 50% response and DCAEs. Results During double-blind treatment periods with galcanezumab 120 mg, NNT to achieve ≥ 30% and ≥ 50% responses ranged from 4 to 10 and NNT to achieve ≥ 75% responses ranged from 5 to 23 in individual trials. NNH ranged from 93 to 1000, while LHH ranged from 18.6 to 104.6. NNTs were generally more robust among patients with EM than with CM; however, in patients with failure of ≥ 2 prior preventive treatments, NNTs to achieve ≥ 30% and ≥ 50% responses were similar between patients with CM and EM. NNHs were imputed as 1000 for both migraine types. Resulting LHHs were 178.8 (EM) and 127 (CM). Conclusion Across 4 trials, galcanezumab 120 mg demonstrated a favorable benefit–risk profile versus placebo, based on low NNTs to achieve response and high NNHs associated with DCAEs. LHH values consistently far exceeded 1. Trial Registration Numbers EVOLVE-1: ClinicalTrials.gov identifier, NCT02614183; EVOLVE-2: ClinicalTrials.gov identifier, NCT02614196; REGAIN: ClinicalTrials.gov identifier, NCT02614261; CONQUER: ClinicalTrials.gov identifier, NCT03559257. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01848-x.

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by thrombotic events and/or pregnancy morbidity (≥3 recurrent early miscarriage or fetal death or a prematurity34 weeks of gestation) with persistently positive antiphospholipid antibodies (aPLs). It is reported that aPLs damage the placental tissue by binding to β2-glycoprotein I (β2GPI) on the surface of trophoblast and endothelial cells. Hydroxychloroquine (HCQ) is considered to be beneficial in the treatment of obstetrical APS and shown to restore the aPL-inhibited invasion and differentiation of trophoblast. However, not enough evidence exists regarding the effect of HCQ on endometrial angiogenesis. The aim of our study was to assess whether HCQ has an effect on aPL-inhibited endothelial angiogenesis.In this research, to explore the effect of HCQ for angiogenesis, we investigated: (1) Human umbilical vein endothelial cells (HUVECs) viability by CCK-8; (2) HUVECs migration by wound healing; (3) HUVEC angiogenesis by Matrigel assayWe found that HCQ treatment significantly restored the expression of aPL-inhibitedIn conclusion, aPLs inhibit HUVECs angiogenesis, however, HCQ can restore the effect of aPL-inhibited HUVECs migration and angiogenesis

Low-to-medium temperature geothermal fluids in the granite regions of southeastern China are an important renewable energy resource, but they are also a source of contamination containing highly toxic elements such as fluoride and arsenic. This study analyzed the origin of the geothermal fluids in a regional-scale hydrogeological unit in the city of Xiamen, China, based on isotope and hydrochemical analyses. The Br/Cl ratios suggested that the inland geothermal fluid is merely recharged by rainwater from the mountain edge, while the coastal geothermal fluid is originally recharged by the seawater and later mixed with rain-derived groundwater. The geothermal water featured high SiO2 and detectable Zn concentrations. The former reflects the significant water–granite interaction along the flow path, and the latter indicates the active hydraulic connection between surface waters, shallow aquifers and deep geothermal fluids. High radon content was detected near the deep conductive fault adjacent to a geothermal well, demonstrating that the fault damage zone acts as a major conduit for upward transport of the deep geothermal fluid. As a result, the fault damage zones developed in the granite are necessary for the formation of geothermal water, which leads to the uneven distribution of geothermal water in the subsurface. High-temperature geothermal water can be found in those regions with fairly sparse fault damage zones. In contrast, in the region with high-density fault activities, the active communication between shallow cool water and deep geothermal fluids can decrease the water temperature.

Bionics provides a positive and beneficial impact on the development of various materials and systems, which has been widely used in energy storage, heat transfer enhancement, and solar thermochemical reactions. In this paper, the idea of heat storage unit with biomimetic alveoli structure is proposed and introduced to increase the heat transfer area and improve the thermal performance of the packed-bed latent heat thermal energy storage (LHTES) system. The effects of heat storage unit structure on temperature distribution, liquid fraction, thermal storage capacity, and other performance indexes of the conventional model and biomimetic model are analyzed. The numerical results indicate that the biomimetic alveoli structure can improve the thermal response of heat storage unit, increase the specific surface area, and achieve a faster heat storage process of the packed-bed compared with the conventional structure. Among various existing models, the double-cell model has a significant improvement. Compared with the conventional model, the maximum increase of liquid fraction and charging efficiency are 9.8% and 6.4%, respectively. This study can provide references to optimize packed-bed LHTES and improve its thermal performance under practical conditions.

Purpose Machine tools are the equipment used for the cutting and shaping of materials, like metals, which generate greenhouse gas (GHG) emissions across their life cycles due to material use and energy consumption. The life cycle emissions of machine tools are distributed over time and may vary with technology advancement. This paper aims to incorporate these temporal factors into the global warming impact (GWI) assessment of machine tools and further reveal their influences on the results. Method Incorporating emission time into the GWI assessment of machine tools is based on the following dynamic life cycle assessment (LCA) framework. First, compute temporally differentiated GHGs of machine tools based on the activity-based modeling. And then, use time-dependent characterization factors (CFs), which are developed based on the radiative forcing concept, to assess their GWI. By using this framework, a dynamic life cycle GWI assessment of machine tool is conducted using two gear hobbing machines. Both the emission time and the potential changes of life cycle emissions due to the improvement of electricity mix and the variation of machine tool use modes are considered. Results and discussion The results demonstrated that when the emission time was considered, both machines offered 3% of reduction of GWI, compared with their static results, respectively. Further reductions were found for the two machines, when the electricity improvement and the changes of the machine tool use modes were considered. All the differences between the static and the dynamic environmental impact results become smaller with the extension of the time horizons (THs) that accounted for the evaluation. Conclusions and recommendations The conventional static LCA has the potential to overestimate the real GWI of machine tools. It is more important to account for the emission time in GWI assessment at shorter THs or for a longer lifetime of machine tools. This work offers a method to dynamically assess the real GWI of machine tools. The proposed method helps to make robust decision-making for environmentally friendly machine tool selection and support sustainable production.

Due the energy resource comes from solar energy, resulting in a high working temperature, radiation field has a significant influence on the energy storage efficiency of the high temperature solar thermochemistry. In order to promote the solar energy conversion efficiency of solar driven steam methane reforming (SMR), the idea of regulate the radiation field to be in accordance with the energy conversion on-demand is proposed and the biomimetic leaf-type hierarchical porous structure solar thermochemical reactor is introduced, which can regulate the spatial distribution of solar radiation intensity and optimize the temperature field. Combined with thermochemical kinetics and Finite Volume Method (FVM), the numerical calculation model of the SMR reaction in a biomimetic solar thermochemical reactor is established to optimize the temperature field. The effects of different reaction conditions and reactor parameters on steam methane reforming hydrogen production are analyzed. The results show that methane conversion in the biomimetic leaf-type solar thermochemical reactor is increased by 4.5%.

Introduction Axial spondyloarthritis (axSpA) is a chronic rheumatic disease affecting the spine and sacroiliac joints, encompassing both ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA) patients. Patient quality of life (QoL) is assessed using the Ankylosing Spondylitis Quality of Life (ASQoL) (disease-specific measure) and the Assessment of SpondyloArthritis International Society Health Index (ASAS HI) (disease-specific measure). Both ASQoL and ASAS HI have similar parameters and scoring ranges, however, their performance relative to each other is unknown. We conducted a cross-walk analysis of the ASAS HI to the ASQoL in AS and nr-axSpA patients. Methods A cross-sectional survey using the Adelphi axSpA Disease Specific Programme™, conducted with rheumatologists and their consulting AS and nr-axSpA patients in the United States, was undertaken between Jun and Aug 2018. Rheumatologists provided confirmed diagnoses of AS and nr-axSpA alongside patients’ demographic and clinical characteristics. Patients reported quality-of-life measures using the validated ASAS HI and ASQoL questionnaires. Model performance was assessed by comparing root-mean squared error (RMSE) from tenfold cross-validation to determine the best mapping from ASAS HI to ASQoL, and vice versa. RMSE was calculated overall, and for lower, middle and upper thirds of the predicted scale. Results Data from 283 AS and 274 nr-axSpA patients were analyzed. Predicting ASAS HI using ASQoL values, the best model was non-parametric local linear regression, with overall RMSE of 1.851. Predicting ASQoL using ASAS HI values, the best model also used non-parametric local-linear regression, with overall RMSE of 2.254. In predicting ASAS HI and ASQoL, models performed better in predicting lower values in the predicted scale (RMSE 1.597, 1.871, 2.871 across thirds for ASAS HI; and 1.719, 2.577, 3.140 for ASQoL). Conclusions Results present a scoring algorithm for cross-walking the ASAS HI to the ASQoL and vice versa, with the approach enabling comparisons to be made across studies.

Prostate cancer susceptibility is a polygenic trait. We aimed to examine the controversial diagnostic utility of single-nucleotide polymorphisms (SNP) for prostate cancer. We analyzed two datasets collected from Europeans and one from Africans. These datasets were generated by the genome-wide association studies, that is, CGEMS, BPC3, and MEC-Africans, respectively. About 540,000 SNPs, including 61 risk markers that constitute a panel termed MK-61, were commonly genotyped. For each dataset, we augmented the MK-61 panel to generate an MK-61+ one by adding several thousands of SNPs that were moderately associated with prostate cancer occurrence in external dataset(s). We assessed the diagnostic utility of both panels by measuring their predictive strength for prostate cancer occurrence with AUC statistics. We calculated the theoretical AUCs using quantitative genetics model-based formulae and obtained the empirical estimates via 10-fold cross-validation using statistical and machine learning techniques. For the MK-61 panel, the 95% confidence intervals of the theoretical AUCs (AUC-CI.95) were 0.578–0.655, 0.596–0.656, and 0.539–0.596 in the CGEMS, BPC3, and MEC-Africans cohorts, respectively. For the MK-61+ panels, the corresponding AUC-CI.95 were 0.617–0.663, 0.527–0.736, and 0.547–0.565. The empirical AUCs largely fell within the theoretical interval. A promising result (AUC = 0.703, FNR = 0.354, FPR = 0.353) was obtained in the BPC3 cohort when the MK-61+ panel was used. In the CGEMS cohort, the MK-61+ panel complemented PSA in predicting the disease status of PSA ≥ 2.0 ng/mL samples. This study demonstrates that augmented risk SNP panels can enhance prostate cancer prediction for males of European ancestry, especially those with {\rm{PSA}} \ge 2.0\ $ng/mL. Prevention Relevance: This study demonstrates that augmented risk SNP panels can enhance prostate cancer prediction for males of European ancestry, especially those with PSA ≥ 2 ng/mL.

To improve the stability and sensitivity of pH sensors based on AlGaN/GaN high electron mobility transistors (HEMTs), we proposed a modified sensing structure by integrating a reference HEMT device. This structural pH sensor exhibits a typical Nernstian behavior with a sensitivity of 54.38 mV/pH, which is higher than the value of 49.43mV/pH derived from the AlGaN/GaN HEMT-based sensor without integrating the reference HEMTs device. Furthermore, the stability of the new structural sensor is enhanced by approximately 19.2% in comparison with that of its traditional counterpart. The improved performances are analyzed using an electrical double-layer model together with an equivalent circuit model, and we find that the new sensor structure has a larger capacitor and exhibits a better rectification effect, hence decreasing the electrical noise and enhancing the stability of the testing signal. Meanwhile, the new sensor structure displays a smaller equivalent resistance and results in a larger available output current, hence exhibiting a higher sensitivity.

Drug addiction remains a key biomedical challenge facing current neuroscience research. In addition to neural mechanisms, the focus of the vast majority of studies to date, astrocytes have been increasingly recognized as an “accomplice.” According to the tripartite synapse model, astrocytes critically regulate nearby pre- and postsynaptic neuronal substrates to craft experience-dependent synaptic plasticity, including synapse formation and elimination. Astrocytes within brain regions that are implicated in drug addiction exhibit dynamic changes in activity upon exposure to cocaine and subsequently undergo adaptive changes themselves during chronic drug exposure. Recent results have identified several key astrocytic signaling pathways that are involved in cocaine-induced synaptic and circuit adaptations. In this review, we provide a brief overview of the role of astrocytes in regulating synaptic transmission and neuronal function, and discuss how cocaine influences these astrocyte-mediated mechanisms to induce persistent synaptic and circuit alterations that promote cocaine seeking and relapse. We also consider the therapeutic potential of targeting astrocytic substrates to ameliorate drug-induced neuroplasticity for behavioral benefits. While primarily focusing on cocaine-induced astrocytic responses, we also include brief discussion of other drugs of abuse where data are available.

The COVID-19 pandemic is the third outbreak this century of a zoonotic disease caused by a coronavirus, following the emergence of severe acute respiratory syndrome (SARS) in 20031 and Middle East respiratory syndrome (MERS) in 20122. Treatment options for coronaviruses are limited. Here we show that clofazimine-an anti-leprosy drug with a favourable safety profile3-possesses inhibitory activity against several coronaviruses, and can antagonize the replication of SARS-CoV-2 and MERS-CoV in a range of in vitro systems. We found that this molecule, which has been approved by the US Food and Drug Administration, inhibits cell fusion mediated by the viral spike glycoprotein, as well as activity of the viral helicase. Prophylactic or therapeutic administration of clofazimine in a hamster model of SARS-CoV-2 pathogenesis led to reduced viral loads in the lung and viral shedding in faeces, and also alleviated the inflammation associated with viral infection. Combinations of clofazimine and remdesivir exhibited antiviral synergy in vitro and in vivo, and restricted viral shedding from the upper respiratory tract. Clofazimine, which is orally bioavailable and comparatively cheap to manufacture, is an attractive clinical candidate for the treatment of outpatients and-when combined with remdesivir-in therapy for hospitalized patients with COVID-19, particularly in contexts in which costs are an important factor or specialized medical facilities are limited. Our data provide evidence that clofazimine may have a role in the control of the current pandemic of COVID-19 and-possibly more importantly-in dealing with coronavirus diseases that may emerge in the future.

Background Nephrotic syndrome (NS) is a common glomerular disease in children. Nursing during hospitalization alone cannot solve the psychological, physiological and social health problems of children. Continuing care models may provide patients with more continuous and efficient care services. Therefore, the present study aimed to provide theoretical support for the implementation and development of children's primary nephrotic syndrome (PNS) and children's chronic disease continuing nursing through the construction of a children's PNS continuing nursing model. Methods Each item of the transitional care model for children with PNS was demonstrated using the Delphi method for two rounds of correspondence. The main items included four components: the composition of personnel, the responsibilities of each member, the content of work, and the evaluation indicators. Results A transitional care model for children with PNS was formed. The expert judgment coefficient of two rounds of correspondence was 0.84, the familiarity degree coefficient was 0.76, the authority degree coefficient was 0.80, the coefficient of variation was between 0.02 and 0.23, and the coordination coefficient was 0.458 and 0.327, respectively (P Conclusions The experts in the present research were highly motivated, had a high degree of authority, and presented consistent opinions. Hence, the construction of a transitional care model for children with PNS is scientifically feasible.

The neuroprotective effects of heme oxygenase (HO) have been well investigated. The potential effects of exogenous supplementation of biliverdin (BVD), one of the main products catalyzed by HO, on neurobehaviors are still largely unknown. The present study aimed to investigate the effects of BVD treatment on depression, anxiety, and memory in adult mice. Mice were injected with BVD through tail vein daily for a total 5 d, and depression- and anxiety-like behaviors were conducted by using open field test (OFT), novelty suppressed feeding (NSF), forced swimming test (FST) and tail suspension test (TST) since the third day of BVD administration. Novel object recognition (NOR) paradigm was used for memory formation test. After the final test, serum and hippocampal levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) of mice were analyzed by enzyme-linked immunosorbent assay (ELISA). The results showed that BVD treatment at low dose (2 mg/kg) induced depression-like behaviors, and high dose (8 mg/kg) BVD injection increased anxiety-like behaviors and impaired memory formation in mice. ELISA data showed that BVD treatment significantly increased hippocampal IL-6 and TNF-α level while only decreasing serum IL-6 level of mice. The present data suggest that exogenous BVD treatment induced depression- and anxiety-like phenotypes, which may be related to inflammatory factors, providing BVD may be a potential target for the prevention of mental disorders.

Background Galcanezumab is a monoclonal antibody (mAb) that binds calcitonin gene-related peptide (CGRP) and is indicated for the preventive treatment of migraine. Galcanezumab demonstrated early onset of effect in patients with migraine but it is unknown whether the same holds true for patients who have not benefited from multiple prior migraine preventives. Methods Patients with episodic or chronic migraine from a 3-month, randomized, double-blind, placebo-controlled, phase 3b study (CONQUER) who had 2 to 4 migraine preventive medication category failures in the past 10 years were randomized 1:1 to placebo (N = 230) or galcanezumab 120 mg/month (240 mg loading dose; N = 232). In this post-hoc analysis, change from baseline in number of monthly and weekly migraine headache days was assessed. Monthly onset of effect was the earliest month at which significant improvement with galcanezumab compared to placebo was achieved and maintained at all subsequent months. Weekly onset was the initial week at which statistical separation was achieved and maintained at all subsequent weeks during that month. Proportion of patients with migraine headache days in the first week of treatment, and patients achieving ≥50%, ≥75%, and 100% response by month and week were also assessed. Results Galcanezumab-treated patients had a significantly greater reduction in monthly migraine headache days starting at month 1, which remained significant for all subsequent months compared to placebo (all p ≤ 0.0001, month 1 mean change from baseline: placebo − 0.7; galcanezumab − 4.0). Weekly migraine headache days was significantly reduced in galcanezumab-treated patients starting at week 1 and continued for each subsequent week of month 1 compared to placebo (all p p p p Conclusion Galcanezumab showed early onset of effect beginning the day after treatment initiation in patients who had not previously benefited from migraine preventive treatments. Trial registration ClinicalTrials.gov, NCT03559257. Registered 18 June 2018.

Mobile money is a service bundled with mobile technology and a social good that promotes financial inclusion for the under-served populations. Although the effect of mobile money has been examined in the past, we look at the supply side effects as it is important for managers to understand the role of mobile money in both providing social good and making a profit. From 1G to 4G mobile technologies, mobile money consistently serves as a competitive advantage for mobile network operators (MNOs). However, this does not mean that the effect stays unchanged over the generations of mobile technology. Instead, when the 3G technology allows web browsing as a major upgrade of mobile functionality, MNOs with mobile money have a substantially larger set of options to differentiate from those without mobile money; and as a result, mobile money implemented with 3G and 4G leads to larger market shares than that with 1G and 2G.

This work presents a novel process to manufacture advanced Germanium-On-Insulator with integrated Silicon Nitride (GOIN) stripes as light waveguide for Ge photonic devices. Through the integration of GOIN stripes, larger tensile strain could be imposed to the bonded Ge layer which may could be used to tailor the bandgap of Ge material for short wave length infrared application. The successful fabrication of advanced GOIN substrate makes the opportunity for monolithic integration of high-performance Ge-based high mobility transistors with photonic components where silicon nitride is the waveguide with low optical loss.

Due to the high working temperature and solar energy is the sole energy resource, radiative transfer field has a significant influence on the solar driven methane reforming conversion efficiency. In order to improve the conversion efficiency of solar driven methane reforming, the idea of using biomimetic venous hierarchical porous structure as solar thermochemical reactor is proposed to regulate the radiative transfer field, which in turn can optimize the temperature field. Through a Finite Volume Method (FVM) combined with thermochemical kinetics, a numerical analysis model of solar driven dry methane reforming (DMR) is established. The effects of different pore diameter combinations (d1, d2, and d3) and partition positions (L1 and R1) on the thermochemical performance of reforming are analyzed. The results show that by introducing a biomimetic venous hierarchical porous structure, the methane conversion can be improved by up to 5.9%, which can provide guidance for the optimal design of the solar thermochemical reactor.

BACKGROUND Computed tomography (CT) has become a routine preoperative examination for tibial plateau fractures (TPFs). Assessing the location of the fragment and intercondylar eminence fracture can provide clinicians with valuable information; however, the evaluation of traumatic meniscal lesion (TML) and arthroscopic management are controversial. AIM To predict TML by three-dimensional skeletal anatomy changes in unilateral TPF and bilateral TPF on preoperative thin layer CT. METHODS Acute fracture of tibial plateau patients undergoing arthroscopic surgery between December 2017 and December 2019 were included in this retrospective study. The type, zone, and location of TMLs were diagnosed based on the operation records and/or arthroscopic videos. Measurement of three-dimensional fracture morphology included the following: Frontal fragment width of plateau, sagittal fragment subsiding distance (FSD), sagittal fracture line distance, sagittal posterior tibial slope, and transversal area ratio of fragment area) on preoperative CT three-dimensional plane. The correlation of TML with skeletal values was calculated according to unicondylar TPFs and bicondylar TPFs. RESULTS A total of 67 patients were enrolled in this study, among which 30 patients had TMLs, lateral/medial (23/7). FSD was a particularly positive factor to predict TML, with odds ratio of 2.31 (1.26-5.63). On sagittal view of CT, FSD degree of 8 mm and posterior tibial slope exceeding 11.74° implied enhanced risk of TML in bicondylar TPFs. On coronal view, once fragment width of plateau surpassed 3 cm, incidence of TML reached 100%. On transverse view, area ratio of fragment as enhanced risk of 5.5% and FSD > 4.3 mm for predicting TML were observed in unicondylar TPFs. CONCLUSION TML can be predicted by different parameters on preoperative CT views according to unicondylar fractures and bicondylar TPFs.

Neonatal hypoxic-ischemic (HI) injury is a severe complication often leading to neonatal death and long-term neurobehavioral deficits in children. Currently, the only treatment option available for neonatal HI injury is therapeutic hypothermia. However, the necessary specialized equipment, possible adverse side effects, and limited effectiveness of this therapy creates an urgent need for the development of new HI treatment methods. Photobiomodulation (PBM) has been shown to be neuroprotective against multiple brain disorders in animal models, as well as limited human studies. However, the effects of PBM treatment on neonatal HI injury remain unclear. Methods: Two-minutes PBM (808 nm continuous wave laser, 8 mW/cm2 on neonatal brain) was applied three times weekly on the abdomen of pregnant rats from gestation day 1 (GD1) to GD21. After neonatal right common carotid artery ligation, cortex- and hippocampus-related behavioral deficits due to HI insult were measured using a battery of behavioral tests. The effects of HI insult and PBM pretreatment on infarct size; synaptic, dendritic, and white matter damage; neuronal degeneration; apoptosis; mitochondrial function; mitochondrial fragmentation; oxidative stress; and gliosis were then assessed. Results: Prenatal PBM treatment significantly improved the survival rate of neonatal rats and decreased infarct size after HI insult. Behavioral tests revealed that prenatal PBM treatment significantly alleviated cortex-related motor deficits and hippocampus-related memory and learning dysfunction. In addition, mitochondrial function and integrity were protected in HI animals treated with PBM. Additional studies revealed that prenatal PBM treatment significantly alleviated HI-induced neuroinflammation, oxidative stress, and myeloid cell/astrocyte activation. Conclusion: Prenatal PBM treatment exerts neuroprotective effects on neonatal HI rats. Underlying mechanisms for this neuroprotection may include preservation of mitochondrial function, reduction of inflammation, and decreased oxidative stress. Our findings support the possible use of PBM treatment in high-risk pregnancies to alleviate or prevent HI-induced brain injury in the perinatal period.

Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) are associated with mild cognitive impairment (MCI). However, this association is unclear. This study aimed to assess the prevalence of MCI in patients with overlap syndrome, determine whether OSA increases the risk of MCI in patients with COPD, and investigate the potential mechanisms for this association.Participants with stable Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2-4 COPD and complaints of snoring in 2016-2018 were enrolled in this cross-sectional observational study. All were free of asthma, acute left-sided congestive heart failure, unstable coronary heart disease, uncontrolled hypertension, diabetes, encephalitis, and epilepsy. They underwent pulmonary function tests and overnight polysomnography and completed the Montreal Cognitive Assessment (MoCA). MCI was defined by an MoCA score of23, while OSA was defined by an apnea-hypopnea index (AHI) of ≥15 per hour. The association between MCI, demographics, and comorbidities was tested by logistic regression analysis with adjustment for confounders. Sleep-disordered breathing measures were investigated as potential mechanisms underlying this relationship.MCI was significantly more common in patients with overlap syndrome than in those with COPD (40.6% [43/106] vs 24.6% [42/171]). After adjustment, severe OSA was an independent contributor to MCI (odds ratio, OR 2.27; 95% confidence interval, CI 1.12-4.62). Increased percent of night-time spent with oxygen saturation90% (TSatMCI is more prevalent in overlap syndrome than in COPD. OSA may contribute to MCI in COPD. The mechanism may involve TSat

Sleep abnormalities are often a prominent contributor to withdrawal symptoms following chronic drug use. Notably, rapid eye movement (REM) sleep regulates emotional memory, and persistent REM sleep impairment after cocaine withdrawal negatively impacts relapse-like behaviors in rats. However, it is not understood how cocaine experience may alter REM sleep regulatory machinery, and what may serve to improve REM sleep after withdrawal. Here, we focus on the melanin-concentrating hormone (MCH) neurons in the lateral hypothalamus (LH), which regulate REM sleep initiation and maintenance. Using adult male Sprague Dawley rats trained to self-administer intravenous cocaine, we did transcriptome profiling of LH MCH neurons after long-term withdrawal using RNA-sequencing, and performed functional assessment using slice electrophysiology. We found that three weeks after withdrawal from cocaine, LH MCH neurons exhibit a wide range of gene expression changes tapping into cell membrane signaling, intracellular signaling, and transcriptional regulations. Functionally, they show reduced membrane excitability and decreased glutamatergic receptor activity, consistent with increased expression of voltage-gated potassium channel gene Kcna1 and decreased expression of metabotropic glutamate receptor gene Grm5. Finally, chemogenetic or optogenetic stimulations of LH MCH neural activity increase REM sleep after long-term withdrawal with important differences. Whereas chemogenetic stimulation promotes both wakefulness and REM sleep, optogenetic stimulation of these neurons in sleep selectively promotes REM sleep. In summary, cocaine exposure persistently alters gene expression profiles and electrophysiological properties of LH MCH neurons. Counteracting cocaine-induced hypoactivity of these neurons selectively in sleep enhances REM sleep quality and quantity after long-term withdrawal.

To elucidate the potential roles of the lncRNA-mediated competitive endogenous RNA (ceRNA) network in the pathogenesis of bronchopulmonary dysplasia (BPD), we performed an integrated bioinformatics analysis based on miRNA and mRNA microarray datasets between BPD and normal samples.The mRNA and miRNA expression profiles of BPD were downloaded from the Gene Expression Omnibus (GEO) database to perform an integrated analysis. The limma package was used to identify differentially expressed genes (DEGs) and differentially expressed miRNA (DEmiRs), followed by functional enrichment analysis of DEGs. DEmiR-DEG and DEmiRNA-lncRNA interactions were predicted. Subsequently, the lncRNA-related ceRNA network was structured. Finally, a newborn BPD mouse model was established, and quantitative real-time PCR (qPCR) was used to validate the expression of the selected mRNAs, miRNAs, and lncRNAs.A total of 445 DEGs and 155 DEmiRs were obtained by comparing BPD samples and normal samples. Functional enrichment analysis showed that DEGs were primarily enriched in GO terms such as cell division and inflammatory response; and DEGs were mainly involved in the p53 signaling pathway. TheThe

Background China has great student participation in STEM education. Chinese society has a progressive and positive attitude towards STEM as it is considered to provide more opportunities in life. Teachers play a vital role in the success of any STEM program in K-12 schools. However, teachers are facing instructional challenges because of the interdisciplinary nature of the STEM curriculum and the current typical school structure. The success of the STEM programs depends on teachers’ beliefs and their knowledge in adapting to instructional implementation of STEM concepts. Results The data (n = 216) was collected from STEM primary and secondary teachers from 25 provinces in mainland China. Exploratory factor analysis (EFA) was applied, and Pearson’s correlation analysis was used to examine the correlation between Chinese STEM teachers’ beliefs, knowledge, implementation, and the intrinsic challenges of STEM education; t tests and analysis of variance (ANOVA) were performed to ascertain whether there were differences. The structural equation model (SEM) was applied to identify interrelationships. The results indicated that Chinese STEM teachers encounter higher-level intrinsic challenges to instructional implementations based on their beliefs and knowledge. Teachers who utilize their experience of teaching science as their main discipline and then attempt to integrate STEM using mathematics and engineering are likely to encounter higher-level intrinsic challenges in implementation. Conclusion The intrinsic challenges perceived by Chinese teachers in the practice of STEM education can be predicted by their beliefs and knowledge base. Teachers who understand the nature and pedagogy of STEM education are more likely to encounter lower-level intrinsic challenges of STEM teaching, while teachers who utilize their main discipline when conducting integrated STEM learning activities through modeling based on science, technology, engineering, and mathematical problem situations are more likely to encounter higher-level intrinsic challenges. This study also reveals that there are some significant differences in the level of STEM teachers’ beliefs, knowledge base, instructional practice, and their intrinsic challenges based on their teaching grade, seniority, and experience of STEM training and teaching.

BACKGROUND Recent research suggests that although prokinetic agents, acid suppressors, and radical treatment for Helicobacter pylori infection may be effective in patients with functional dyspepsia (FD), a large proportion of patients still fail to respond to these treatments or may suffer from severe adverse reactions. Many traditional Chinese medicinal herbs can regulate the status of the entire body and have special advantages in the treatment of functional diseases. The present study was designed to verify the efficacy of Biling Weitong Granules (BLWTG), a traditional Chinese medicinal herbal compound formula, in alleviating epigastric pain syndrome (EPS) in FD patients, in an attempt to provide an effective prescription for the clinical treatment of this disease. AIM To evaluate the clinical efficacy and safety of BLWTG in treating EPS in patients with FD. METHODS In this multicenter, stratified, randomized, double-blind, placebo-controlled, parallel group clinical trial, eligible patients were randomized into the BLWTG and placebo groups who were treated for 6 wk. Efficacy indicators including the severity and frequency of EPS and the time to pain resolution and safety indicators including adverse events were observed and compared. RESULTS The baseline demographic data and clinical characteristics, such as epigastric pain symptoms, pain intensity, and frequency of attacks, were matched between the two groups before randomization. After 6 wk of treatment and after the center effect was eliminated, the epigastric pain was significantly improved in 28.33% and 85.59% of the patients in the placebo and BLWTG groups, respectively (P < 0.05). At 6 wk, the resolution rate of epigastric pain was 15% and 69.49% in the placebo and BLWTG groups, respectively (P < 0.05). The differences of total FD clinical score between these two groups were significant (P < 0.05) at 2, 4, and 6 wk (P < 0.05). The scores of each item and the total score in the Functional Digestive Disorders Quality of Life Questionnaire showed significant differences between the two groups at 6 wk after both the center and interaction effects were eliminated (P < 0.05). There was no significant difference in the incidence of adverse events between the two groups, and no serious adverse event was noted during the observation. CONCLUSION Compared with placebo, BLWTG markedly improved EPS in FD patients without causing serious adverse reactions.

A poor prognosis, relapse and resistance are burning issues during adverse-risk acute myeloid leukaemia (AML) treatment. As a natural medicine, Scutellaria barbata D. Don (SBD) has shown impressive antitumour activity in various cancers. Thus, SBD may become a potential drug in adverse-risk AML treatment. This study aimed to screen the key targets of SBD in adverse-risk AML using the drug-biomarker interaction model through bioinformatics and network pharmacology methods. First, the adverse-risk AML-related critical biomarkers and targets of SBD active ingredient were obtained from The Cancer Genome Atlas database and several pharmacophore matching databases. Next, the protein-protein interaction network was constructed, and topological analysis and pathway enrichment were used to screen key targets and main pathways of intervention of SBD in adverse-risk AML. Finally, molecular docking was implemented for key target verification. The results suggest that luteolin and quercetin are the main active components of SBD against adverse-risk AML, and affected drug resistance, apoptosis, immune regulation and angiogenesis through the core targets AKT1, MAPK1, IL6, EGFR, SRC, VEGFA and TP53. We hope the proposed drug-biomarker interaction model provides an effective strategy for the research and development of antitumour drugs.

Background Some authors state that above-normal surface electromyography (SEMG) levels during mandibular rest (MR) are a general sign of temporomandibular disorders (TMD). Objective The aim was to compare SEMG levels in the masseter and anterior temporalis areas during MR between patients with disc displacement (DD) and subjects identified as healthy. The hypothesis was that average SEMG levels would be higher in the patients during MR before and after repeated clenches with maximal effort. Methods Thirty-six healthy subjects, and 42 patients with DD, were included. SEMG levels were recorded bilaterally in the temporalis and masseter areas during MR before clenching and after repeated clenches with maximal effort. Multivariate analysis of variance (MANOVA) was used to compare the means of the log-transformed SEMG-values for the subject groups. Results The mean MR levels in the four areas before clenching ranged from -0.19 log (µV) to 1.20 log(µV) in healthy subjects and from -0.22 log(µV) to 0.96 log(µV) in patients. The mean MR levels in the four areas after repeated clenches ranged from -0.19 log (µV) to 1.04 log(µV) in healthy subjects and from -0.27 log(µV) to 0.93 log(µV) in patients. The MANOVA test showed no significant differences in the means for MR for the four areas between the groups at the 5% significance level. Conclusion The hypothesis that jaw muscle SEMG levels during MR are on average generally higher in TMD patients is not supported. A possible explanation for the previous findings is that activity in other muscles was mislabelled as jaw muscle activity.

The emergence of new media technologies has empowered individuals to not merely consume but also create, share and critique media contents. Such activities are dependent on new media literacy (NML)...

Life cycle impact assessment (LCIA) is a lively field of research, and data and models are continuously improved in terms of impact pathways covered, reliability, and spatial detail. However, many of these advancements are scattered throughout the scientific literature, making it difficult for practitioners to apply the new models. Here, we present the LC‐IMPACT method that provides characterization factors at the damage level for 11 impact categories related to three areas of protection (human health, ecosystem quality, natural resources). Human health damage is quantified as disability adjusted life years, damage to ecosystem quality as global species extinction equivalents (based on potentially disappeared fraction of species), and damage to mineral resources as kilogram of extra ore extracted. Seven of the impact categories include spatial differentiation at various levels of spatial scale. The influence of value choices related to the time horizon and the level of scientific evidence of the impacts considered is quantified with four distinct sets of characterization factors. We demonstrate the applicability of the proposed method with an illustrative life cycle assessment example of different fuel options in Europe (petrol or biofuel). Differences between generic and regionalized impacts vary up to two orders of magnitude for some of the selected impact categories, highlighting the importance of spatial detail in LCIA. This article met the requirements for a gold – gold JIE data openness badge described at http://jie.click/badges., Journal of Industrial Ecology, 24 (6), ISSN:1088-1980, ISSN:1530-9290

Targeting the androgen receptor (AR) signalling pathway remains the main therapeutic option for advanced prostate cancer. However, resistance to AR‐targeting inhibitors represents a great challenge, highlighting the need for new therapies. Activation of the PI3K/AKT pathway and increased expression of histone deacetylases (HDACs) are common aberrations in prostate cancer, suggesting that inhibition of such targets may be a viable therapeutic strategy for this patient population. Previous reports demonstrated that combination of PI3K inhibitors (PI3KIs) with histone deacetylase inhibitors (HDACIs) resulted in synergistic antitumour activities against preclinical models of prostate cancer. In this study, we demonstrate that the novel dual PI3K and HDAC inhibitor CUDC‐907 has promising antitumour activity against prostate cancer cell lines in vitro and castration‐resistant LuCaP 35CR patient‐derived xenograft (PDX) mouse model in vivo. CUDC‐907‐induced apoptosis was partially dependent on Mcl‐1, Bcl‐xL, Bim and c‐Myc. Further, down‐regulation of Wee1, CHK1, RRM1 and RRM2 contributed to CUDC‐907‐induced DNA damage and apoptosis. In the LuCaP 35CR PDX model, treatment with CUDC‐907 resulted in significant inhibition of tumour growth. These findings support the clinical development of CUDC‐907 for the treatment of prostate cancer.

Lysophosphatidic acid (LPA), a ubiquitous phospholipid, plays a crucial role in the pathogenesis and pathophysiological process of neurological diseases, which constitute the pathological course after cerebral ischemia. Nevertheless, the molecular mechanisms associated with the pathogenic roles of LPA remain elusive. In this study, we evaluated the expression of the liver X receptor (LXR) and nuclear factor kappa B (NFκB) by Western blotting, quantified the levels of IL-1β, IL-6, TNF-α, and LPA by ELISA, and evaluated apoptosis and infarct by TUNEL (terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling) and TTC (triphenyltetrazolium chloride) staining respectively in Sprague-Dawley (SD) rats after middle cerebral artery occlusion (MCAO). The levels of LPA, an extracellular signaling molecule, increased after ischemia and caused neurological injury effect, decreased the expression level of LXR, and increased the expression level of inflammatory factors (IL-1β, IL-6, and TNF-α) via the NFκB signaling pathway. This elevated LPA-induced pathological process is one of the pathological reactions associated with ischemic brain injury. We present a direct or indirect connection between LPA and LXR in the pathophysiological process. In conclusion, we speculate that the inhibition of LPA generation and administration of LXR agonist may be explored as potential cerebral infarction treatment strategies.

Despite the widespread use of antiplatelets and anticoagulants, women with antiphospholipid syndrome (APS) may face pregnancy complications associated with placental dysplasia. Neutrophil extracellular traps (NETs) are involved in the pathogenesis of many autoimmune diseases, including vascular APS; however, their role in obstetric APS is unclear. Herein, we investigated the role of NETs by quantifying cell‐free DNA and NET marker levels. Live‐cell imaging was used to visualize NET formation, and MAPK signalling pathway proteins were analysed. Cell migration, invasion and tube formation assays were performed to observe the effects of NETs on trophoblasts and human umbilical vein endothelial cells (HUVECs). The concentrations of cell‐free DNA and NETs in sera of pregnant patients with APS were elevated compared with that of healthy controls (HCs) matched to gestational week. APS neutrophils were predisposed to spontaneous NET release and IgG purified from the patients (APS‐IgG) induced neutrophils from HCs to release NETs. Additionally, APS‐IgG NET induction was abolished with inhibitors of reactive oxygen species, AKT, p38 MAPK and ERK1/2. Moreover, NETs were detrimental to trophoblasts and HUVECs. In summary, APS‐IgG‐induced NET formation deserves further investigation as a potential novel therapeutic target in obstetrical APS.

A pioneering epidemic study has revealed a strong association between obesity and the risk of colitis. In this study, a high fat diet was found to significantly aggravate colitis induced by dextran sulfate sodium (DSS). Meanwhile, a high fat diet changed the miRNA profile of the visceral adipose exosomes, switching the exosomes from anti-inflammatory to a pro-inflammatory phenotype. Strikingly, these inflammatory exosomes efficiently circulated into the lamina propria of the intestine, while these exosomes predisposed the intestine to inflammation via promoting macrophage M1 polarization. Mechanistically, the exosomes promoted M1 differentiation at least partially via transferring pro-inflammatory miRNAs, such as miR-155. Moreover, exosome-mediated miR-155 inhibitor delivery significantly prevented DSS-induced colitis. Together, the study has revealed an exosomal pathway of how obesity aggravates colitis and proposes an exosome-based intervention strategy for colitis management.

A major racial disparity in prostate cancer (PCa) is that African American (AA) patients have a higher mortality rate than European American (EA) patients. We filtered the SEER 2009–2011 records and divided them into four groups regarding patient races and cancer grades. On such a partition, we performed a series of statistical analyses to further clarify the aforementioned disparity. Molecular evidence for a primary result of the epidemiological analysis was obtained from gene expression data. The results include: (1) Based on the registry-specific measures, a significant linear regression of total mortality rate (as well as PCa specific mortality rate) on the percentage of (Gleason pattern-based) high-grade cancers (PHG) is demonstrated in EAs (p