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Background: Gastric cancer (GC) is one of the most common malignant tumors of the digestive system. As a hallmark of cancer, energy-related metabolic reprogramming was manipulated by various factors, including lncRNAs. It has been shown that lncRNA CCAT1 is a key regulator involved in tumor development. Nevertheless, the exact underlying molecular mechanisms by which lncRNA CCAT1 acts in GC metabolic reprogramming are yet to be elucidated. Methods: The expression of CCAT1 in GC tissues, serum, and exosome that was isolated from plasma and GC cell lines were detected by qRT-PCR. The gain and loss-function assays were performed to explore the role of CCAT1 on GC cells. Xenograft tumor formation models in nude mice were performed to estimate the proliferation of GC cells with CCAT1 stably knocking down in vivo. The proteins interacting with CCAT1 were first analyzed by online databases and further confirmed by RNA pull-down and RNA immunoprecipitation (RIP) assays. The expression of glycolytic signaling pathway-related proteins were probed using western blotting and immunohistochemistry (IHC). Results: In this study, we identified that CCAT1 was remarkably enhanced in the tissues, serum, and plasma exosomes of GC patients as well as in GC cell lines. Functional experiments showed that knockdown of CCAT1 significantly reduced the proliferation, migration and invasion of GC cells in vitro and in vivo, and also decreased glycolytic rate and the expression of glycolytic enzymes in GC cells, whereas overexpression of CCAT1 had opposing effects. Mechanically, CCAT1 interacted with PTBP1 and maintained its stability by inhibiting the ubiquitin-mediated degradation. As a critical splicing factor, PTBP1 induced a switch from PKM1 to PKM2, leading to an increase in the glycolysis of GC cells and ultimately promoting GC progression. Conclusions: Our study exhibited that CCAT1 contributed to GC proliferation, migration and invasion via PTBP1 / glycolysis axis, making it a potential biomarker and therapeutic target in GC patients.

In order to effectively evaluate the structural safety of water-rich tunnel in the construction process, two indexes of groundwater and lining safety reserve were introduced, and the seven factor evaluation index system of water-rich tunnel structural safety was constructed. The fuzzy evaluation method based on comprehensive weighted algorithm was put forward and applied to a water-rich tunnel project in Southwest China. The results showed that: (1) the constructed index system is more systematic and comprehensive. (2) The proposed evaluation method can effectively reduce the subjectivity of expert scoring and improve the accuracy and rationality of results. (3) The safety evaluation grade of tunnel calculated by this method is consistent with the current safety state of the project, indicating that this study has certain practicability.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by diverse serological autoantibodies. Anti-dsDNA antibodies are involved in multiple organ damage, especially the kidney, skin, and central nervous system. Anti-dsDNA antibodies play a pivotal role in SLE, and researchers have developed therapeutic strategies targeting these antibodies. Approaches to reduce anti-dsDNA antibodies via B cell targeted biologics against B cell surface antigens, B cell survival factors, or Bruton’s tyrosine kinase have effectively eliminated B cells. However, their non-specific depletion hampers normal immune system functioning and limits the therapeutic benefits. Thus, scientists have attempted anti-dsDNA antibodies or lupus-specific strategies, such as the immature dendritic cell vaccine and immunoadsorption. Recently, synthetic mimic peptides (hCDR1, pCONs, DWEYS, FISLE-412, and ALW) that directly block anti-dsDNA autoantibodies have attracted attention, which could ameliorate lupus, decrease the serological autoantibody titer, reduce the deposition of renal autoantibodies, and improve pathological performance. These potent small peptide molecules are well tolerated, non-toxic, and non-immunogenic, which have demonstrated a benign safety profile and are expected to be hopeful candidates for SLE management. In this review, we clarify the role of anti-dsDNA antibodies in SLE, mainly focus on the current strategies targeting anti-dsDNA antibodies, and discuss their potential clinical value.

It is a pressing need, but still challenging to explore the structure and function of membrane proteins (MPs). One of the main obstacles is the limited availability of matched detergents for the handling of specific MPs. We describe herein the design of new detergents by incorporation of a transition linker between the hydrophilic head and the hydrophobic tail. This design allows a gradual change of hydrophobicity between the outside and inside of micelles, in contrast to the abrupt switch in conventional detergents. Notably, many of these detergents assembled into micelles in while retaining low critical micelle concentrations. Meanwhile, thermal stabilizing evaluation identified superior detergents for representative MPs, including G protein-coupled receptors and a transporter protein. Among them, further improved the NMR study of MPs. We anticipate these that results will encourage future detergent expansion through new remodeling on the traditional detergent scaffold.

As a proinflammatory cytokine, tumor necrosis factor-like weak inducer of apoptosis (TWEAK) participates in the progression of renal fibrosis by binding to 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 aimed 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 expression 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 Notch1/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.

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...

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.

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

Exposure to traffic-related particulate air pollution has been linked with excess risks for a range of cardiovascular, respiratory and neurological health outcomes; risks likely to be exacerbated in young children attending schools adjacent to highly-trafficked roads. One immediate way of reducing airborne PM concentrations at the local (i.e., near-road community) scale is installation of roadside vegetation as a means of passive pollution abatement. Roadside vegetation can decrease airborne PM concentrations, through PM deposition on leaves, but can also increase them, by impeding airflow and PM dispersion. Critical to optimizing PM removal is selection of species with high particle deposition velocity (Vd) values, currently under-parameterised in most modelling studies. Here, the measured amounts of leaf-deposited magnetic PM after roadside greening (‘tredge’) installation, and measured reductions in playground PM, particle number and black carbon concentrations demonstrate that air quality improvements by deposition can be achieved at the local, near-road, community/playground scale. PM deposition on the western red cedar tredge removed ~ 49% of BC, and ~ 46% and 26% of the traffic-sourced PM2.5 and PM1, respectively. These findings demonstrate that roadside vegetation can be designed, installed and maintained to achieve rapid, significant, cost-effective improvement of air quality by optimising PM deposition on plant leaves.

BackgroundTumor-associated macrophages (TAMs) are a major component of the tumor microenvironment (TME) and exert an important role in tumor progression. Due to the heterogeneity and plasticity of TAMs, modulating the polarization states of TAMs is considered as a potential therapeutic strategy for tumors. Long noncoding RNAs (lncRNAs) have been implicated in various physiological and pathological processes, yet the underlying mechanism on how lncRNAs manipulate the polarization states of TAMs is still unclear and remains to be further investigated.MethodsMicroarray analyses were employed to characterize the lncRNA profile involved in THP-1-induced M0, M1 and M2-like macrophage. Among those differentially expressed lncRNAs, NR_109 was further studied, for its function in M2-like macrophage polarization and the effects of the condition medium or macrophages mediated by NR_109 on tumor proliferation, metastasis and TME remodeling both in vitro and in vivo. Moreover, we revealed how NR_109 interacted with far upstream element-binding protein 1 (FUBP1) to regulate the protein stability through hindering ubiquitination modification by competitively binding with JVT-1. Finally, we examined sections of tumor patients to probe the correlation among the expression of NR_109 and related proteins, showing the clinical significance of NR_109.ResultsWe found that lncRNA NR_109 was highly expressed in M2-like macrophages. Knockdown NR_109 impeded IL-4 induced M2-like macrophage polarization and significantly reduced the activity of M2-like macrophages to support the proliferation and metastasis of tumor cells in vitro and in vivo. Mechanistically, NR_109 competed with JVT-1 to bind FUBP1 at its C-terminus domain, impeded the ubiquitin-mediated degradation of FUBP1, activatedc-Myctranscription and thus promoted M2-like macrophages polarization. Meanwhile, as a transcription factor, c-Myc could bind to the promoter of NR_109 and enhance the transcription of NR_109. Clinically, high NR_109 expression was found in CD163+TAMs from tumor tissues and was positively correlated with poor clinical stages of patients with gastric cancer and breast cancer.ConclusionsOur work revealed for the first time that NR_109 exerted a crucial role in regulating the phenotype-remodeling and function of M2-like macrophages via a NR_109/FUBP1/c-Myc positive feedback loop. Thus, NR_109 has great translational potentials in the diagnosis, prognosis and immunotherapy of cancer.

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.

G protein-coupled receptors (GPCRs) are a large membrane protein family found in higher organisms, including the human body. GPCRs mediate cellular responses to diverse extracellular stimuli and thus control key physiological functions, which makes them important targets for drug design. Signaling by GPCRs is related to the structure and dynamics of these proteins, which are modulated by extrinsic ligands as well as by intracellular binding partners such as G proteins and arrestins. Here, we review some basics of using nuclear magnetic resonance (NMR) spectroscopy in solution for the characterization of GPCR conformations and intermolecular interactions that relate to transmembrane signaling., Molecules, 27 (9), ISSN:1420-3049

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.

Trajectory planning and obstacle avoidance play essential roles in the cooperative flight of multiple unmanned aerial vehicles (UAVs). In this paper, a unified framework for onboard distributed trajectory planning is proposed, which takes full advantage of intelligent discrete and continuous search algorithms. Firstly, the Monte Carlo tree search (MCTS) is used as the task allocation algorithm to solve the cooperative obstacle avoidance problem. Taking the task allocation decisions as the constraint, knowledge-based particle swarm optimization (Know-PSO) is used as the optimization algorithm to solve the onboard distributed cooperative trajectory planning problem. Simulation results demonstrate that the proposed intelligent MCTS-PSO search framework is effective and flexible for multiple UAVs to conduct the cooperative trajectory planning and obstacle avoidance. Further, it has been applied in practical experiments and achieved promising results.

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.

Partial-linear single-index models have been widely studied and applied, but their current applications to time series modeling still need some strong and inappropriate assumptions. A novel method which relaxes those assumptions is proposed. It extends the applicability of partial-linear single-index models to time series modeling, taking both lag variables and autocorrelated errors into consideration. An estimation procedure based on Whittle likelihood is proposed and some asymptotical properties of the corresponding estimators are derived. In addition, some simulation studies are conducted to elaborate that the proposed model is necessary in certain situations. The proposed models are also shown to be useful and reasonable in real data analysis, indicating the feasibility and practicability of the proposed estimation method.

Atmospheric particulate matter (PM) has been of concern owing to its negative effects on human health and its role in environmental degradation. For mitigation purposes, it is important to select the most efficient plant species in urban greening. Here, a fast, cost-saving methodology was first added to the conventional method to investigate the size-resolved PM retention capacity and efficiency of twenty plant species. Surface PM (SPM), which can be removed by water and brushing, accounted for 44.9–66.9% of total PM, in which the water-soluble PM (DPM) accounted for 12.9–22.1% of total PM. A large mass proportion of in-wax PM (14.1–31.7%) was also observed. Platycladus orientalis, Eriobotrya japonica, Viburnum odoratissimum, Magnolia grandiflora had the highest AEleaf (retention efficiency on per unit leaf area) to retain SPM within different diameter classes (DPM, PM0.1–2.5, PM2.5–10, PM&gt, 10). AEplant (retention efficiency of individual tree) varied greatly among different plant species, mainly due to the dependence on the total area of a tree. AEland (retention efficiency on per unit green area) is a suitable index for PM retention ability and efficiency. In general, P. orientalis, V. odoratissimum, Pittosporum tobira, Photinia serrulate, M. grandiflora, E. japonica were the efficient species in retaining PM at different scales (i.e., leaf, individual tree, green area). The species like Trifolium repens, Phyllostachys viridis, were the least efficient plant species. The investigated species are all evergreen species, which will remove PM throughout the whole year, even in winter. So, we recommended that the plant species with the highest PM retention efficiency can be used in urban greening. Meanwhile, horticulture practices should also be considered to improve the leaf area index to improve their PM retention and air purification abilities.

Background Stomach adenocarcinoma (STAD), which accounts for approximately 95% of gastric cancer types, is a malignancy cancer with high morbidity and mortality. Tumor angiogenesis plays important roles in the progression and pathogenesis of STAD, in which long noncoding RNAs (lncRNAs) have been verified to be crucial for angiogenesis. Our study sought to construct a prognostic signature of angiogenesis-related lncRNAs (ARLncs) to accurately predict the survival time of STAD. Methods The RNA-sequencing dataset and corresponding clinical data of STAD were acquired from The Cancer Genome Atlas (TCGA). ARLnc sets were obtained from the Ensemble genome database and Molecular Signatures Database (MSigDB, Angiogenesis M14493, INTegrin pathway M160). A ARLnc-related prognostic signature was then constructed via univariate Cox and multivariate Cox regression analysis in the training cohort. Survival analysis and Cox regression were performed to assess the performance of the prognostic signature between low- and high-risk groups, which was validated in the validation cohort. Furthermore, a nomogram that combined the clinical pathological characteristics and risk score conducted to predict the overall survival (OS) of STAD. In addition, ARLnc-mRNA coexpression pairs were constructed with Pearson’s correlation analysis and visualized to infer the functional annotation of the ARLncs by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The expression of four ARLncs in STAD and their correlation with the angiogenesis markers, CD34 and CD105, were also validated by RT–qPCR in a clinical cohort. Results A prognostic prediction signature including four ARLncs (PVT1, LINC01315, AC245041.1, and AC037198.1) was identified and constructed. The OS of patients in the high-risk group was significantly lower than that of patients in the low-risk group (p p Conclusion Our study constructed a prognostic signature consisting of four ARLnc genes, which was closely related to the survival of STAD patients, showing high efficacy of the prognostic signature. Thus, the present study provided a novel biomarker and promising therapeutic strategy for patients with STAD.

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.

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.

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