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To improve the forging safety of powder-forged products, the hot-deformation behaviour of sintered and forged alloys was investigated and compared in the present study. The results show that the fo...

Background: Electronic cigarettes (e-cigarettes) use was reported associated with sleep disturbances, and marijuana was a double-edged sword to sleep. Literature about their dual use is limited. This study aimed to investigate the association between dual use of,e-cigarettes and marijuana and sleep duration among US adults.Methods: This cross-sectional study included 6,573 participants aged 18–64 years from 2015 to 2018. Data were obtained from the National Health and Nutrition Examination Survey database. The chi-square test and analysis of variance were used for analyses of binary and continuous variables, respectively. Multinomial logistic regression models were used for univariate and multivariate analyses of e-cigarettes, marijuana use, and sleep duration. Sensitivity analyses were conducted in populations with dual e-cigarette and traditional cigarette use and those with dual marijuana and traditional cigarette use.Results: Dual e-cigarette and marijuana users had significantly higher odds of not having the recommended sleep duration than those who were using neither (short sleep duration: odds ratio [OR], 2.34; 95% confidence interval [CI], 1.19–4.61; P = 0.014; long sleep duration: OR, 2.09; 95% CI, 1.53–2.87; P < 0.001, respectively) and short sleep duration than only e-cigarette users (OR, 4.24; 95% CI, 1.75–4.60; P < 0.001) in the adjusted model. Dual traditional cigarette and marijuana users had significantly higher odds of long sleep duration than neither users.Conclusions: The study suggested that the dual use of tobacco products and marijuana was associated with sleep duration, which is not recommended, and results differ based on the type of tobacco products. Since the majority of tobacco users use not only one kind of tobacco product, it is important to conduct longitudinal RCTs to explore the joint effect of dual tobacco use on human health.

To compare the image quality and hepatic metastasis detection of low-dose deep learning image reconstruction (DLIR) with full-dose filtered back projection (FBP)/iterative reconstruction (IR).A contrast-detail phantom consisting of low-contrast objects was scanned at five CT dose index levels (10, 6, 3, 2, and 1 mGy). A total of 154 participants with 305 hepatic lesions who underwent abdominal CT were enrolled in a prospective non-inferiority trial with a three-arm design based on phantom results. Data sets with full dosage (13.6 mGy) and low dosages (9.5, 6.8, or 4.1 mGy) were acquired from two consecutive portal venous acquisitions, respectively. All images were reconstructed with FBP (reference), IR (control), and DLIR (test). Eleven readers evaluated phantom data sets for object detectability using a two-alternative forced-choice approach. Non-inferiority analyses were performed to interpret the differences in image quality and metastasis detection of low-dose DLIR relative to full-dose FBP/IR.The phantom experiment showed the dose reduction potential from DLIR was up to 57% based on the reference FBP dose index. Radiation decreases of 30% and 50% resulted in non-inferior image quality and hepatic metastasis detection with DLIR compared to full-dose FBP/IR. Radiation reduction of 70% by DLIR performed inferiorly in detecting small metastases (1 cm) compared to full-dose FBP (difference: -0.112; 95% confidence interval [CI]: -0.178 to 0.047) and full-dose IR (difference: -0.123; 95% CI: -0.182 to 0.053) (p0.001).DLIR enables a 50% dose reduction for detecting low-contrast hepatic metastases while maintaining comparable image quality to full-dose FBP and IR.• Non-inferiority study showed that deep learning image reconstruction (DLIR) can reduce the dose to oncological patients with low-contrast lesions without compromising the diagnostic information. • Radiation dose levels for DLIR can be reduced to 50% of full-dose FBP and IR for detecting low-contrast hepatic metastases, while maintaining comparable image quality. • The reduction of radiation by 70% by DLIR is clinically acceptable but insufficient for detecting small low-contrast hepatic metastases (1 cm).

Despite the continuous efforts, the current repertoire of detergents is still far from sufficient for the biophysics studies of membrane proteins (MPs). Toward the rapid expansion of detergent diversity, we herein report a new strategy based on Ugi reaction mediated modular assembly. Structural varieties, including hydrophobic tails and hydrophilic heads, could be conveniently introduced from the multiple reaction components. New detergents then were comprehensively evaluated in the physical properties and preliminarily screened by the thermal stabilization for a transporter MsbA and a spectrum of G protein-coupled receptors (GPCRs). For the glucagon-like peptide-1 receptor (GLP-1R), a class B GPCR, detergent M-23-M finally stood out in a second evaluation for the maintenance of homogeneity and was further illustrated its application in the improvement of NMR study. Besides the promising utility in the MP study, the current results exhibit intriguing structural-physical relationship that would allow the guidance in the tuning of detergent properties in the future.

Detergents are the most frequently applied reagents in membrane protein (MP) studies. The limited diversity of one-head-one-tailed traditional detergents, however, is far from sufficient for structurally distinct MPs. Expansion of detergent repertoire has a continuous momentum. In line with the speculation that detergent pre-assembly exerts superiority, herein we report for the first time cross-conjugation of two series of monomeric detergents for constructing a two-dimensional library of dimeric detergents. Optimum detergents stood out with unique preferences in the systematic evaluation of individual MPs. Furthermore, unprecedented hybrid detergents 14M8G and 14M9G enabled high-quality EM study of transporter MsbA and NMR study of G protein-coupled receptor A

The human glucagon-like peptide-1 receptor (GLP-1R) and the glucagon receptor (GCGR) are class B G protein-coupled receptors (GPCRs) that are activated by interactions with, respectively, the glucagon-like peptide-1 (GLP-1) and glucagon (GCG). These polypeptide hormones are involved in the regulation of lipid and cholic acid metabolism, and thus play an important role in the pathogenesis of glucose metabolism and diabetes mellitus, which attracts keen interest of these GPCRs as drug targets. GLP-1R and GCGR have therefore been extensively investigated by X-ray crystallography and cryo-electron microscopy (cryo-EM), so that their structures are well known. Here, we present the groundwork for using nuclear magnetic resonance (NMR) spectroscopy in solution to complement the molecular architectures with information on intramolecular dynamics and on the thermodynamics and kinetics of interactions with physiological ligands and extrinsic drug candidates. This includes the generation of novel, near-wild-type constructs of GLP-1R and GCGR, optimization of the solution conditions for NMR studies in detergent micelles and in nanodiscs, post-translational chemical introduction of fluorine-19 NMR probes, and sequence-specific assignments of the 19 F-labels attached to indigenous cysteines. Addition of the negative allosteric modulator (NAM) NNC0640 was critically important for obtaining the long-time stability needed for our NMR experiments, and we report on novel insights into the allosteric effects arising from binding of NNC0640 to the transmembrane domain of GLP-1R (GLP-1R[TMD]).

A growing body of studies examined the effects of health shocks during early childhood and in-utero in developing countries. However, the related research on mental health is limited. In this artic...

A growing corpus of evidence implicates the involvement of the commensal microbiota and immune cytokines in the initiation and progression of systemic lupus erythematosus (SLE). Glucocorticoids have been widely used in the treatment of SLE patients, however, glucocorticoid treatment carries a higher risk of other diseases. Using the 16S rRNA technique, we investigated the differences between the gut microbiota associated with the immune cytokines of SLE and relevant glucocorticoid treatment in a female cohort of 20 healthy control subjects (HC), 17 subjects with SLE (SLE-G), and 20 SLE patients having undergone glucocorticoid treatment (SLE+G). We observed that the diversity and structure of the microbial community in SLE+G patients were significantly changed compared to that of SLE-G patients, whereas the gut microbial community of the SLE+G group showed a similarity with the HC group, which implicate that the shift in the gut microbiome could represent a return to homeostasis. Furthermore, the up-regulations of immune cytokines in SLE-G were identified as closely related to gut dysbiosis, which indicates that the overrepresented genera in SLE patients may play roles in regulating expression level of these immune cytokines. This associated analysis of gut microbiota, glucocorticoid therapy, and immune factors might provide novel and insightful clues revealing the pathogenesis of SLE patients.

Background The STAT3/HIF-1α/VEGF pathway is associated with the development and progress of various tumors including NSCLC. The aim of the present study was to investigate whether resveratrol (RES) could suppress NSCLC progression via inhibiting the expressions of STAT3, HIF-1α, and VEGF in a nude rat model. Methods Twenty-four nude rats were randomly divided into control, NSCLC, and NSCLC+RES groups. An orthotopic rat model of NSCLC was established. The animals in the NSCLC+RES group received the same operation as the NSCLC group and were intragastrically administered RES at 250 mg/kg/day for 12 weeks. Lung tissue samples were harvested for gross tumor burden measurement, histological examinations, RT-PCR, and Western blot assays. Results In the NSCLC+RES group, significant decreases in lung weight index, lung tumor burden, STAT3/HIF-1α/VEGF mRNA, and protein levels were observed when compared with the NSCLC group (all P

Background 5-aminolaevulinic acid (ALA)-based photodynamic therapy (ALA-PDT) is an effective treatment for proliferative skin diseases. Many studies revealed that ALA-PDT induces apoptosis of cancer cells. However, the mechanism of PDT in warts is not fully elucidated. Objective This study was designed to explore the efficacy of ALA-PDT for plantar warts and its possible mechanism. Methods Twenty-five patients with plantar warts underwent four rounds of ALA-PDT at weekly intervals. Therapeutic effects were observed 1 month since last treatment. The adverse reactions were also recorded during and after the procedure. To observe histological changes, 5 patients accepted tissue biopsies before and 24 h after first PDT treatment. Results Twenty-two patients (88%) showed a complete response. Twenty patients complained of a mild burning sensation during treatment, and four patients developed local edema immediately after red light exposure. Five patients had burns after treatment, which disappeared within 24 h. Histologically, epidermal keratinocytes demonstrated remarkable necrocytosis and apoptosis after PDT. Conclusions ALA-PDT is highly effective for treatment of plantar warts. The most common adverse effects observed in patients are pain and edema. ALA-PDT might eradicate plantar warts by activating both necrosis and apoptosis to trigger the death of proliferating keratinocytes.

Clinical studies have established that the capacity of removing excess fluid from alveoli is impaired in most patients with acute respiratory distress syndrome. Impaired alveolar fluid clearance (AFC) correlates with poor outcomes. Adenosine A2B receptor (A2BAR) has the lowest affinity with adenosine among four adenosine receptors. It is documented that A2BAR can activate adenylyl cyclase (AC) resulting in elevated cAMP. Based on the understanding that cAMP is a key regulator of epithelial sodium channel (ENaC), which is the limited step in sodium transport, we hypothesized that A2BAR signaling may affect AFC in acute lung injury (ALI) through regulating ENaC via cAMP, thus attenuating pulmonary edema. To address this, we utilized pharmacological approaches to determine the role of A2BAR in AFC in rats with endotoxin-induced lung injury and further focused on the mechanisms in vitro. We observed elevated pulmonary A2BAR level in rats with ALI and the similar upregulation in alveolar epithelial cells exposed to LPS. A2BAR stimulation significantly attenuated pulmonary edema during ALI, an effect that was associated with enhanced AFC and increased ENaC expression. The regulatory effects of A2BAR on ENaC-α expression were further verified in cultured alveolar epithelial type II (ATII) cells. More importantly, activation of A2BAR dramatically increased amiloride-sensitive Na+ currents in ATII cells. Moreover, we observed that A2BAR activation stimulated cAMP accumulation, whereas the cAMP inhibitor abolished the regulatory effect of A2BAR on ENaC-α expression, suggesting that A2BAR activation regulates ENaC-α expression via cAMP-dependent mechanism. Together, these findings suggest that signaling through alveolar epithelial A2BAR promotes alveolar fluid balance during endotoxin-induced ALI by regulating ENaC via cAMP pathway, raising the hopes for treatment of pulmonary edema due to ALI.

Chlorpyrifos (CPF) is an extensively used organophosphorus pesticide. Recently, it has attracted increasing attention due to environmental health problems caused by it. Although numerous studies have discovered the dechlorinated photoproduct of CPF, its structure and toxicity remain largely unknown. In this study, we systematically investigated the structure and toxicity of dechlorinated photoproduct of CPF. The CPF degradation experiment was performed, and its products were identified by ultra high performance liquid chromatography-orbitrap fusion tribid mass spectrometer (UHPLC-Orbitrap Fusion TMS). Additionally, bond dissociation energy (BDE) calculations and photoproduct chemical synthesis were employed to determine the structure of dechlorinated photoproduct of CPF. The toxicity of CPF photoproduct was evaluated through the Ecological Structure Activity Relationships (ECOSAR) Class Program, the Toxicity Estimation Software Tool (T.E.S.T.) software, and acute toxicity testing. The results indicated that the dechlorinated photoproduct of CPF was identified as O,O-Diethyl-O-(3,5-dichloro-2-pyridyl) phosphorothioate (Dechloro-CPF), which was produced in large quantity within the first 30 min of photodegradation experiment. The acute and chronic toxicity values of Dechloro-CPF were obviously higher than those for the other two photoproducts. The median lethal dose (LD

An analytical method based on high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF/MS) was established for the rapid screening and identification of 62 kinds of illegally added traditional Chinese medicine (TCM) in food. According to the notice of the Ministry of Health of the People's Republic of China on further regulating the management of raw materials of health food (Weifa Jianfa (2002) No. 51), the characteristic components of the 62 kinds of TCM were screened, and the corresponding characteristic component lists of different TCM were obtained. Methanolic extracts of the 62 kinds of standard medicinal materials were subjected to HPLC-Q-TOF-MS analysis. The filtrate was separated on a Thermo Accucore aQ column (150 mm×2.1 mm, 2.6 μm) using 0.1%(v/v) formic acid aqueous solution or water and acetonitrile as the mobile phases for gradient elution in the electrospray positive and negative ion scanning mode. All the data were determined on the full scan of primary mass spectrometry and secondary mass spectrometry, with mass acquisition ranges of 100-1000 Da and 50-1000 Da, respectively. A 10 mmol/L sodium formate solution was used as the mass correction solution in both the positive and negative ion modes. Library View software was used to establish the precursor ion accurate quality database and the product ion fragment mass spectrometry database of the corresponding characteristic components of the different kinds of TCM. In the Library View database software, the name of each characteristic component of the 62 kinds of TCM was input (serial number) in order to classify the screened characteristic components. The samples were processed using the same method and analyzed. Peak View software was used to rapidly analyze and screen the target components of the TCM. The high-resolution data collected from the samples to be tested were imported into the Peak View software, followed by the compound list of the established MS database of standard medicinal materials. After setting the identification method parameters and library retrieval parameters, a matching analysis was performed, and the candidate substances for each peak were automatically identified by comparing the mass spectrum, accurate molecular ion mass number, fragment ion mass number, retention time, and other related parameters. The determination conditions of compound detection were as follows: the comprehensive score was more than 70 points. The molecular formula, retention time, mass spectrum as well as the primary isotope mass spectrometry, primary mass spectrometry, and secondary mass spectrometry data were matched with the library compounds. The corresponding list of "TCM-characteristic components" was established, and a high-resolution MS library of 388 characteristic components from the 62 types of TCM was constructed. Each TCM contains 5-10 characteristic components. According to the screening analysis of the actual food samples of the prepared wine, substitute tea, and beverage, one batch of the prepared wine sample matched with seven characteristic components of epimedium, and it was inferred that epimedium was added to the prepared wine samples. This method can allow for the qualitative screening of TCM without standards and has the characteristics of high throughput, accuracy, simplicity, and rapidity. It solves the difficulty in identifying and confirming illegally added TCM in food; provides technical methods and a basis for cracking down on the illegal addition of TCM in food; and facilitates the rapid screening and identification of illegally added TCM in food.

In the context of the mobile Internet, continuously upgraded media and increasing numbers of terminal devices has enabled information communication to become instant and abundant. The lifestyle of the public has also changed with the evolution of the Internet. The public’s growing enthusiasm for watching short videos on smart phones are one example. This paper discusses changes in the communication environment, namely the concept and development of mobile short videos. Application of Lasswell’s “5W” model to mobile short video communication, is used to analyze this form of communication, using Meipai, a Chinese mobile short video application, as a case study. Suggestions for potential development in this area are also considered.

Soil contamination with toxic metals and metalloids has become a major threat to global food security. Among various immobilization agents that can stabilize toxic metal(loid)s effectively, biochar is promising due to its ability to restore soil health. Yet the aging characteristics of biochar following its amendment in soil remain poorly explored. Therefore, this study used standard biochars to depict their aging effects on remediation of metal(loid)-contaminated soil. A total of 2304 observations were made, including 6 biochar feedstocks (rice husk, soft wood, oilseed rape straw, miscanthus straw, sewage sludge and wheat straw), 2 pyrolysis temperatures (550 °C, 700 °C), 8 metal(loid)s (Mn, Ni, Cu, Zn, As, Cd, Sb, Pb), 4 aging methods (natural aging, freeze-thaw cycling, wet-dry cycling, chemical oxidation with H

Summary Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) acts through its receptor fibroblast growth factor inducible 14 (Fn14), and participates in skin inflammation. Both TWEAK and Fn14 are highly expressed in skin lesions of patients with atopic dermatitis. The purpose of this study was to further explore the effect of Fn14 inhibition on experimental atopic dermatitis. Experimental atopic dermatitis was induced in the wild-type and Fn14 knock-out BALB/c mice. The effect of TWEAK/Fn14 interaction on keratinocytes was studied in an in-vitro model of atopic dermatitis. Fn14 deficiency ameliorates skin lesions in the mice model, accompanied by less infiltration of inflammatory cells and lower local levels of proinflammatory cytokines, including TWEAK, TNF-α and interleukin (IL)-17. Fn14 deficiency also attenuates the up-regulation of TNFR1 in skin lesions of atopic dermatitis. Moreover, topical TWEAK exacerbates skin lesion in the wild-type but not in the Fn14 knock-out mice. In vitro, TWEAK enhances the expressions of IL-17, IL-18 and IFN-γ in keratinocytes under atopic dermatitis-like inflammation. These results suggest that Fn14 deficiency protects mice from experimental atopic dermatitis, involving the attenuation of inflammatory responses and keratinocyte apoptosis. In the context of atopic dermatitis-like inflammation, TWEAK modulates keratinocytes via a TNFR1-mediated pathway.

In this study, multilayer perceptron artificial neural networks are used to predict orthodontic treatment plans, including the determination of extraction-nonextraction, extraction patterns, and anchorage patterns. The neural network can output the feasibilities of several applicable treatment plans, offering orthodontists flexibility in making decisions. The neural network models show an accuracy of 94.0% for extraction-nonextraction prediction, with an area under the curve (AUC) of 0.982, a sensitivity of 94.6%, and a specificity of 93.8%. The accuracies of the extraction patterns and anchorage patterns are 84.2% and 92.8%, respectively. The most important features for prediction of the neural networks are “crowding, upper arch” “ANB” and “curve of Spee”. For handling discrete input features with missing data, the average value method has a better complement performance than the k-nearest neighbors (k-NN) method; for handling continuous features with missing data, k-NN performs better than the other methods most of the time. These results indicate that the proposed method based on artificial neural networks can provide good guidance for orthodontic treatment planning for less-experienced orthodontists.

In view of the multi-UAV cooperative area coverage search problem, the analysis and simplification are carried out. A number of improvement measures are proposed on the basis of the classic genetic algorithm to improve the adaptability of the algorithm and adapt to the engineering application. The “zero-adding method” and the “negative number method” are mainly proposed. These two encoding methods are used to simulate and verify the optimization solution of a typical scene. The simulation results prove that both methods achieve the balance of search optimization accuracy and speed. Among them, the effect of the “negative number method” is slightly better than the “zero-filling method”.

As a proinflammatory cytokine, tumor necrosis factor-like weak inducer of apoptosis (TWEAK) participates in the progression of renal fibrosis by engaging its receptor, fibroblast growth factor-inducible 14 (Fn14). However, the effect of Fn14 inhibition on tubular epithelial cell-mediated tubulointerstitial fibrosis remains unclear. This study was designed to elucidate the role of TWEAK/Fn14 interaction in the development of experimental tubulointerstitial fibrosis as well as the protective effect of Fn14 knockdown on proximal tubular epithelial cells. A murine model of unilateral ureteral obstruction was constructed in both wild-type and Fn14-deficient BALB/c mice, followed by observation of the tubulointerstitial pathologies. Fn14 deficiency ameliorated the pathological changes, including inflammatory cell infiltration and cell proliferation, accompanied by reduced production of profibrotic factors and extracellular matrix deposition. In vitro experiments showed that TWEAK dose-dependently enhanced the expressions of collagen I, fibronectin, and α-smooth muscle actin in proximal tubular epithelial cells. Interestingly, TWEAK also upregulated the expression levels of Notch1/Jagged1. Fn14 knockdown and Notch/Jagged1 inhibition also mitigated the effect of TWEAK on these cells. In conclusion, TWEAK/Fn14 signals contributed to tubulointerstitial fibrosis by acting on proximal tubular epithelial cells. Fn14 inhibition might be a therapeutic strategy for protecting against renal interstitial fibrosis.

The human glucagon-like peptide-1 receptor (GLP-1R) and the glucagon receptor (GCGR) are class B G protein-coupled receptors (GPCRs) that are activated by interactions with, respectively, the glucagon-like peptide-1 (GLP-1) and glucagon (GCG). These polypeptide hormones are involved in the regulation of lipid and cholic acid metabolism, and thus play an important role in the pathogenesis of glucose metabolism and diabetes mellitus, which attracts keen interest of these GPCRs as drug targets. GLP-1R and GCGR have therefore been extensively investigated by X-ray crystallography and cryo-electron microscopy (cryo-EM), so that their structures are well known. Here, we present the groundwork for using nuclear magnetic resonance (NMR) spectroscopy in solution to complement the molecular architectures with information on intramolecular dynamics and on the thermodynamics and kinetics of interactions with physiological ligands and extrinsic drug candidates. This includes the generation of novel, near-wild-type constructs of GLP-1R and GCGR, optimization of the solution conditions for NMR studies in detergent micelles and in nanodiscs, post-translational chemical introduction of fluorine-19 NMR probes, and sequence-specific assignments of the

The intelligent combat of aircraft has become an important research area. This paper studies the 1Vs1 pursuit-evasion game confrontation scenario of the aircraft, aiming to enable the red agent to find the optimal strategy to avoid the blue interception. First, the aircraft is abstracted into an agent, the kinematics model of the aircraft is simplified, and the behavior model of the aircraft with the bait throwing behavior is established. Based on the improved DQN algorithm, with relative distance, line-of-sight angle and azimuth as the state; the reward function design comprehensively considers the time, number of bait throwing, maneuvering time, and miss distance, and proposes an aircraft pursuit-evasion game algorithm (RB-DQN) in a three-dimensional environment. Experimental results show that the algorithm can effectively control the aircraft to complete the escape mission, and has satisfactory generalization.

Clinical studies have established that the capacity of removing excess fluid from alveoli is impaired in most patients with acute respiratory distress syndrome. Impaired alveolar fluid clearance (AFC) correlates with poor outcomes. Adenosine A

Atherosclerosis (AS) is a serious threat to the health and life of humans worldwide. The mitigating effect of polyphenol compounds from peanut skin extract (PSE) on AS has attracted great research attention. However, the mechanism underlying this mitigating effect remains poorly understood. This study aims to investigate the preventive effect of PSE on high-fat diet-induced AS in mice and explore the underlying mechanisms. PSE treatment significantly reduced atherosclerotic plaques, particularly at high doses. Dietary PSE intervention obviously alleviated the lipid metabolism disorder in ApoE

Particulate matter (PM) in different size fractions (PM0.1–2.5, PM2.5–10 and PM>10) accumulation on four tree species (Populus tomentosa, Platanus acerifolia, Fraxinus chinensis, and Ginkgo biloba) at two sites with different pollution levels was examined in Beijing, China. Among the tested tree species, P. acerifolia was the most efficient species in capturing PM, followed by F. chinensis, G. biloba, and P. tomentosa. The heavily polluted site had higher PM accumulation on foliage and a higher percentage of PM0.1–2.5 and PM2.5–10. Encapsulation of PM within cuticles was observed on leaves of F. chinensis and G. biloba, which was further dominated by PM2.5. Leaf surface structure explains the considerable differences in PM accumulation among tree species. The amounts of accumulated PM (PM0.1–2.5, PM2.5–10, and PM>10) increased with the increase of stomatal aperture, stomatal width, leaf length, leaf width, and stomatal density, but decreases with contact angle. Considering PM accumulation ability, leaf area index, and tolerance to pollutants in urban areas, we suggest P. acerifolia should be used more frequently in urban areas, especially in “hotspots” in city centers (e.g., roads/streets with heavy traffic loads). However, G. biloba and P. tomentosa should be installed in less polluted areas.

The aim of this study was to determine the expression and significance of miR-126 and miR-145 in endometrial tissues in the mid-luteal phase of patients with infertility due to endometriosis. It was an experimental study carried out from January 2016 to July 2017. A total of 47 infertile patients with endometriosis were selected as an endometriosis group, and classified as 22 cases (46.81%) in stage I-II and 25 cases (53.19%) in stage III-IV; while 47 women who were infertile due to male factors were selected as a control group. The research showed that the expression levels of miR-126 and miR-145 in endometriosis group were higher than those of the control group (both p

BACKGROUND AND AIMS To identify the efficacy and safety of remifentanil when compared with other opioids in adult critically ill patients. METHODS We searched for studies in the Cochrane Library, MEDLINE, and EMBASE that had been published up to May 31st, 2019. Randomized clinical trials using remifentanil comparing with other opioids for analgesia were included. Two reviewers independently applied eligibility criteria, assessed quality, and extracted data. Duration of mechanical ventilation was the primary outcome, and secondary outcomes included weaning time, intensive care unit (ICU), length of stay (LOS), hospital LOS, mortality, side effects, and costs. RESULTS Fifteen studies with 1233 patients were included. Remifentanil was associated with a significant reduction in the duration of mechanical ventilation in the adult ICU patients when compared with other opioids (P = .01). Remifentanil also reduced the weaning time (P = .02) and the ICU LOS when compared with other opioids (P = .01). There was no difference in the hospital LOS (P = .15), side effects (P = .39), and mortality (P = .79) between remifentanil and other opioids, what's more, remifentanil increased the costs of anesthesia (P

Oxidative stress is an important pathogenic factor in various hepatic diseases. Nuclear factor-erythroid 2-related factor-2 (Nrf2), which coordinates the expression of an array of antioxidant and detoxifying genes, has been proposed as a potential target for prevention and treatment of liver disease. Dibenzoylmethane (DBM) is a minor ingredient in licorice that activates Nrf2 and prevents various cancers and oxidative damage. In the present study, the mechanisms by which DBM activates Nrf2 signaling were delineated, and its protective effect against carbon tetrachloride (CCl4)-induced liver injury was examined. DBM potently induced the expression of HO-1 in cells and in the livers of mice, but this induction was diminished in Nrf2-deficient mice and cells. Overexpression of Nrf2 enhanced DBM-induced HO-1 expression, while overexpression of a dominant-negative fragment of Nrf2 inhibited this induction. DBM treatment resulted in dissociation from Keap1 and nuclear translocation of Nrf2. Moreover, DBM activated Akt/protein kinase B, mitogen-activated protein kinases, and AMP-activated protein kinase and increased intracellular calcium levels. Inhibition of JNK, AMPK, or intracellular calcium signaling significantly suppressed the induction of HO-1 expression by DBM. Finally, DBM treatment significantly inhibited CCl4-induced acute liver injury in wild-type but not in Nrf2-deficient mice. Taken together, our results revealed the mechanisms by which DBM activates Nrf2 and induces HO-1 expression, and provide molecular basis for the design and development of DBM and its derivatives for prevention or treatment of liver diseases by targeting Nrf2.

Reversible protein acetylation, one of the key types of post-translational modifications, is composed of histone acetylation and deacetylation, which is typically catalyzed by histone acetyltransferases (HATs) and histone deacetylases (HDACs) respectively. Herein, a label-free fluorescent method has been established for the homogeneous bioassay of HAT/HDAC activity and respective inhibitors. The proposed approach is primarily based on the electrostatic interaction between G-quadruplexes (G4s) and acetylation-related peptides, which results in marked change of fluorescent intensity of G4/Thioflavin T (ThT) complexes. This HAT (p300) activity assay is exceedingly sensitive and selective, with a linear range from 0.1 to 120nM and a detection limit of 0.05nM. Moreover, this biosensor is feasible to detect the HDAC (Sirt1) activity with a linear range from 1 to 450nM and a detection limit of 1nM. The potency of this assay is further demonstrated by detecting HAT/HDAC activity in cell lysates and evaluating HAT and HDAC-targeted inhibitors, C464 and EX 527, respectively. The proposed assay is convenient, label-free and cost-efficient, which is promising for HAT/HDAC-targeted epigenetic research and pharmaceutical development.

To investigate the characteristics and failure risk factors of sequential high-flow nasal cannula oxygen therapy (HFNC) after weaning from invasive ventilation.The patients who received sequential HFNC after weaning from invasive ventilation admitted to surgical intensive care unit (ICU) of Peking University People's Hospital from June 1st 2016 to May 31st 2018 were retrospectively analyzed. Clinical variables, respiratory therapy parameters, respiratory variables, cardiac variables and outcomes were reviewed and analyzed. Treatment characteristics of HFNC after weaning was analyzed. Patients were divided into HFNC success group and HFNC failure group according to the failure of HFNC, and the differences between the two groups were compared. The independent risk factors of HFNC treatment failure were analyzed by Logistic regression analysis. The value of predictive treatment failure of risk factors and regression models were analyzed by receiver operating characteristic (ROC) curve.A total of 99 patients were included, 61 men, and the median age was 67.0 (57.0, 76.0) years old. The medianinitial HFNC flow was 50 (50, 60) L/min, and inspired oxygen concentration (FiOHFNC is one of the commonly used oxygen therapy methods in the ICU, but not all patients who are treated as a sequential therapy after invasive mechanical ventilation weaning can benefit from it. SOFA score, BNP before HFNC treatment and HR after 30 minutes HFNC treatment were independent risk factors of HFNC failure. Each independent risk factor and regression model can predict the success of HFNC treatment.

Disulfide-containing detergents (DCDs) are introduced, which contain a disulfide bond in the hydrophobic tail. DCDs form smaller micelles than corresponding detergents with linear hydrocarbon chains, while providing good solubilization and reconstitution of membrane proteins. The use of this new class of detergents in structural biology is illustrated with solution NMR spectra of the human G protein-coupled receptor A2A AR, which is an α-helical protein, and the β-barrel protein OmpX from E. coli.

Background Accurate assessment of systemic lupus erythematosus (SLE) disease activity is critical. Currently existing indices or measures for assessment are either expensive, intricate, or inaccurate. The novel indices with higher sensitivity and specificity have become one of the aims of the investigators. This study was designed to explore the relationship between serum tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and systemic lupus erythematosus disease activity index (SLEDAI) as well as its role in guiding glucocorticoid dosages in the treatment of SLE. Of 59 patients with SLE, 20 patients with subacute cutaneous lupus erythematosus (SCLE), 13 patients with discoid lupus erythematosus (DLE) and 32 healthy volunteers, soluble TWEAK level was determined in both serum and urine. Monomeric C-reactive protein, antinuclear antibody, interleukin 6, complements, erythrocyte sedimentation rate, and white blood cells were measured in serum samples. Moreover, SLEDAI-2K was used for evaluating the disease. Finally, methylprednisolone was administrated orally to SLE patients with the doses depending on serum TWEAK levels. Results We found that serum TWEAK levels are higher in patients with SLE (383.0 ± 45.37 ng/ml, p < 0.001 for both) or SCLE (129.1 ± 25.73 ng/ml, p < 0.05 for both) than in patients with DLE (78.38 ± 22.85 ng/ml) or in healthy controls (78.38 ± 22.85 ng/ml). Also, serum TWEAK levels correlate positively with SLEDAI-2K in patients with SLE (r2 = 0.101, p < 0.001), whereas urine TWEAK levels reflect renal damage in patients with lupus nephritis. Moreover, serum TWEAK levels had a higher correlation coefficient with SLEDAI-2K scores compared with the other serum parameters. Furthermore, TWEAK-based glucocorticoid therapy is associated with lower SLEDAI-2K scores and fewer flares in patients with SLE. Conclusions Serum TWEAK is a useful biomarker reflecting SLE disease, and monitoring of serum TWEAK levels can improve the outcomes of glucocorticoid therapy for patients with SLE.

Human exposure to airborne ultrafine (?1 μm) particulate pollution may pose substantial hazards to human health, particularly in urban roadside environments where very large numbers of people are frequently exposed to vehicle-derived ultrafine particles (UFPs). For mitigation purposes, it is timely and important to quantify the deposition of traffic-derived UFPs onto leaves of selected plant species, with particularly efficient particle capture (high deposition velocity), which can be installed curbside, proximal to the emitting vehicular sources. Here, we quantify the size-resolved capture efficiency of UFPs from diesel vehicle exhaust by nine temperate-zone plant species, in wind tunnel experiments. The results show that silver birch (79% UFP removal), yew (71%), and elder (70.5%) have very high capabilities for capture of airborne UFPs. Metal concentrations and metal enrichment ratios in leaf leachates were also highest for the postexposure silver birch leaves; scanning electron microscopy showed that UFPs were concentrated along the hairs of these leaves. For all but two species, magnetic measurements demonstrated substantial increases in the concentration of magnetic particles deposited on the leaves after exposure to the exhaust particulates. Together, these new data show that leaf-deposition of UFPs is chiefly responsible for the substantial reductions in particle numbers measured downwind of the vegetation. It is critical to recognize that the deposition velocity of airborne particulate matter (PM) to leaves is species-specific and often substantially higher (?10 to 50 times higher) than the "standard" V d values (e.g., 0.1-0.64 cm s -1 for PM 2.5) used in most modeling studies. The use of such low V d values in models results in a major under-estimation of PM removal by roadside vegetation and thus misrepresents the efficacy of selected vegetation species in the substantial (≫20%) removal of PM. Given the potential hazard to health posed by UFPs and the removal efficiencies shown here (and by previous roadside measurements), roadside planting (maintained at or below head height) of selected species at PM "hotspots" can contribute substantially and quickly to improve in urban air quality and reductions in human exposure. These findings can contribute to the development and implementation of mitigation policies of traffic-derived PM on an international scale.

In recent years, with the introduction of national, provincial and municipal policies, rules and regulations, and the introduction of big data technology, drug control personnel have further increased their awareness of data. However, in practice, how to carefully control drugs and make full use of big data technology to improve the level of control has become a new confusion for drug control personnel. Therefore, the purpose of this paper is to study the platform of auxiliary drug control based on big data. Based on the actual situation of drug use, this paper analyzes the main problems in the process of drug control, and designs an auxiliary drug control platform based on big data. The auxiliary drug management and control platform based on big data proposed in this paper can collect data in real time, comprehensively analyze all kinds of information, and realize intelligent management and improve the efficiency of each specific application scenario. In this paper, through the research of drug use management and control platform, doctors can get scientific guidance in formulating drug use plan, and the efficiency of drug query is improved by about 80% compared with the traditional plan. At the same time, the drug use plan can be improved in time according to the patient’s illness development in the process of drug use, which promotes the rational and standardized clinical application of drugs.

Psoriasis is a common chronic inflammatory dermatitis in which various cytokines play a detrimental role. The cytokine tumor necrosis factor-related weak inducer of apoptosis (TWEAK) is involved in the pathogenesis of multiple inflammatory disorders. However, the potential role of TWEAK in various subtypes of psoriasis has not been studied in depth. To investigate whether the levels of TWEAK are associated with clinical traits and the levels of some known psoriasis-related cytokines, such as interleukin (IL)-17A, IL-22, interferon (IFN)-γ, and IL-36γ, 20 patients with psoriasis vulgaris (PV), 8 patients with pustular psoriasis (PP), 8 patients with erythrodermic psoriasis (EP), and 20 healthy controls (HCs) were recruited into this study. The levels of serum cytokines were detected by commercial enzyme-linked immunosorbent assay kits. The average levels of TWEAK, IL-17A, IL-22, IFN-γ, and IL-36γ were significantly higher in the psoriasis groups than in the HC group. Furthermore, there was a statistically significant correlation between TWEAK and IL-17A/IFN-γ in PV and IL-36γ in EP, but there was no correlation between TWEAK and IL-22 in any subtype of psoriasis. This study suggests that TWEAK may have a role in the pathogenesis of PV, PP, and EP via synergy with IL-17A, IFN-γ, or IL-36γ, but not with IL-22.

Citrate synthase (CS) is one of the key metabolic enzymes in the Krebs tricarboxylic acid (TCA) cycle. It regulates energy generation in mitochondrial respiration by catalysing the reaction between oxaloacetic acid (OAA) and acetyl coenzyme A (Ac-CoA) to generate citrate and coenzyme A (CoA). CS has been shown to be a biomarker of neurological diseases and various kinds of cancers. Here, a label-free fluorescent assay has been developed for homogeneously detecting CS and its inhibitor based on the in situ generation of CoA-Au(I) co-ordination polymer (CP) and the fluorescence signal-on by SYBR Green II-stained CoA-Au(I) CP. Because of the unique property of the CoA-Au(I) CP, this CS activity assay method could achieve excellent selectivity and sensitivity, with a linear range from 0.0033 U/μL to 0.264 U/μL and a limit of detection to be 0.00165 U/μL. Meanwhile, this assay method has advantages of being facile and cost effective with quick detection. Moreover, based on this method, a biomimetic logic system was established by rationally exploiting the cascade enzymatic interactions in TCA cycle for chemical information processing. In the TCA cycle-derived logic system, an AND-AND-AND-cascaded gate was rigorously operated step by step in one pot, and is outputted by a label-free fluorescent signal with visualized readout.

Background: The aim of this study is to assess the effect of body mass index (BMI) on outcomes of in vitro fertilization (IVF) / intracytoplasmic sperm injection (ICSI) among polycystic ovarian syndrome (PCOS) and non-PCOS patients. Methods: This was a retrospective cohort study that was performed in the Second Hospital of Hebei Medical University. Patients who were under 35 years old were included in the study and were divided into four groups based on their BMI. The number of retrieved oocytes, implantation rate, clinical pregnancy rate, miscarriage rate and live births among PCOS and non-PCOS patients were compared between different BMIs. Results: IVF/ICSI pregnancies in obese PCOS women had a considerably higher risk of miscarriage and low rate of clinical pregnancy than in non-obese PCOS pregnancies. However, in non-PCOS patient, obesity significantly elevated miscarriage rate but did not affect clinical pregnancy rate. Conclusion: Obesity in PCOS patients led to poor outcomes of IVF/ICSI.

Recruitment of antibodies in human immune systems for targeted destruction of tumor cells has emerged as an exciting area of research due to its low occurrence of side effects, high efficacy, and high specificity. The presence of large amounts of anticarbohydrate natural antibodies in human sera has prompted research efforts to utilize carbohydrate epitopes for immune recruitment. Here, we have developed a general strategy for specific targeted destruction of tumor cells based on rhamnose-functionalized liposomes. Tumor cells artificially decorated with rhamnose epitopes were subjected to complement-mediated cytotoxicity in vitro and showed delayed tumor growth in vivo. This study highlights the therapeutic potential for activation of endogenous immune response through cell-surface glycan engineering.

The normal operation of the substation is inseparable from the important guarantee of the cable. The cables in the substation are not only widely distributed, but also the cables are flammable and spread easily after fire. Once a cable catches fire, the consequences will be disastrous. Therefore, how to fire the cable becomes an important task for the power system. Many engineers and technicians continue to analyze and study the causes of cable fires, but cable fire accidents still occur from time to time. In order to solve the problem of cable fire protection and existing problems, the article combines actual research and analysis, and gives the most effective and safe cable fire protection method．

We provide the first study estimating the causal effect of air pollution on body weight and obesity. Using the China Health and Nutrition Survey, which contains detailed longitudinal health and socioeconomic information for 13,741 adult individuals over 1989–2015, we find significant positive effects of air pollution, instrumented by thermal inversions, on body weight. Specifically, a 1 ​μg/m3 (1.54%) increase in average PM2.5 concentrations in the past 12 months increases body mass index by 0.27%, and also increases overweight and obesity rates by 0.82 and 0.27 percentage points, respectively. We also find evidence that these impacts can be explained in part by a variety of behavioral channels, including less physical activity, less walking to work or school, less sleep, and more fat intake.

Additional file 2: Figure S1. Representative images of antibody staining by immunohistochemistry are shown, which showed markedly decreased IgG deposition in the glomeruli of ALW-treated MRL/lpr mice, but no difference in IgM deposition between groups. Scale bar = 50 μm, Figure S2. Serum anti-dsDNA antibodies are not altered in MRL/lpr mice. There were no significant differences in the titers of anti-dsDNA IgM (a), anti-dsDNA IgG (b), anti-dsDNA IgG1 (c), anti-dsDNA IgG2a (d), anti-dsDNA IgG2b (e), anti-dsDNA IgG3 (f) (p > 0.05), Figure S3. Tubulointerstitial changes are attenuated in ALW-treated MRL/lpr mice. a Representative kidney sections (stained with H&E, PAS, Masson, and Ki-67) showed less tubulointerstitial damage in ALW-treated MRL/lpr mice. b Representative images of CD3, B220, and Iba-1 staining showed fewer inflammatory cells in ALW-treated MRL/lpr mice. Scale bar = 50 μm, Figure S4. Proteinuria, renal function parameters, and lymph node scores are comparable in different groups of MRL/lpr mice. The urine levels of microalbumin (a), creatinine (b), and urea nitrogen (c) were measured after 6-week treatment. The serum levels of creatinine (d) and urea nitrogen (e) were determined accordingly. At the same time point, lymph nodes were scored in all mice (f). There were no significant differences in any parameter between these four groups (p > 0.05)., Figure S5. Representative images of immunohistochemical staining demonstrated evidently decreased expressions of TGF-β1 and collagen I in kidneys of ALW-treated mice. Scale bar = 50 μm, Figure S6. Profibrotic cytokines were attenuated in serum of ALW-treated MRL/lpr mice. Serum of TGF-β1 (a), PDGF-B (b), and CTGF (c) were much lower in the mice of the ALW group. The serum levels of TGF-β1 (d), PDGF-B (e), and CTGF (f) correlated positively with renal chronicity index. *p