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Abstract Background Mast cells are being increasingly recognized as critical components in the tumor microenvironment. Protein Kinase D (PKD) is essential for the progression of prostate cancer, but its role in prostate cancer microenvironment remains poorly understood. Methods The expression of PKD, mast cells and microvessel density were examined by IHC. The clinical significance was determined by statistical analyses. The biological function of PKD and the underlying mechanisms were investigated using in vitro and in vivo models. Results PKD2/3 contributed to MCs recruitment and tumor angiogenesis in the prostate cancer microenvironment. Clinical data showed that increased activation of PKD at Ser744/748 in prostate cancer was correlated with mast cell infiltration and microvascular density. PKD2/3 silencing of prostate cancer cells markedly decreased MCs migration and tube formation of HUVEC cells. Moreover, PKD2/3 depletion not only reduced SCF, CCL5 and CCL11 expression in prostate cancer cells but also inhibited angiogenic factors in MCs. Conversely, exogenous SCF, CCL5 and CCL11 reversed the effect on MCs migration inhibited by PKD2/3 silencing. Mechanistically, PKD2/3 interacted with Erk1/2 and activated Erk1/2 or NF-κB signaling pathway, leading to AP-1 or NF-κB binding to the promoter of scf, ccl5 and ccl11. Finally, PKD-specific inhibitor significantly reduced tumor volume and tumor growth in mice bearing RM-1 prostate cancer cells, which was attributed to attenuation of mast cell recruitment and tumor angiogenesis. Conclusions These results demonstrate a novel PKDs function that contributes to tumor angiogenesis and progression through mast cells recruitment in prostate cancer microenvironment.

Plant protection unmanned aerial vehicles (UAVs) play a crucial role in agricultural aviation services. In recent years, plant protection UAVs, which improve the accuracy and eco-friendliness of agricultural techniques, have been used to overcome the shortcomings of traditional agricultural operations. First, this paper introduces the development scale, main types, and operation scenarios of China’s plant protection UAVs. Subsequently, the key technologies of plant protection UAVs, such as precision autonomous flight control, pesticide spraying, drift control, and spraying quality measurement technologies, are reviewed. Next, the emergent technologies of plant protection UAVs are studied and analyzed with a focus on better spray effects, calculation models of droplet drift, controllable droplet size atomization technology, droplet drift detection technology, and droplet deposition quality detection technology in the application of plant protection UAVs. Moreover, the technologies of plant protection UAV application are summarized and future research prospects are presented, offering ideas for follow-up research on the key technologies of plant protection UAVs and encouraging agricultural production management to move toward better efficiency, eco-friendliness, and accuracy.

Aiming at the current situation of network embedding research focusing on dynamic homogeneous network embedding and static heterogeneous information network embedding but lack of dynamic information utilization, this paper proposes a dynamic heterogeneous information network embedding method based on the meta-path and improved Rotate model; this method first uses meta-paths to model the semantic relationships involved in the heterogeneous information network, then uses GCNs to get local node embedding, and finally uses meta-path-level aggression mechanisms to aggregate local representations of nodes, which can solve the heterogeneous information utilization issues. In addition, a temporal processing component based on a time decay function is designed, which can effectively handle temporal information. The experimental results on two real datasets show that the method has good performance in networks with different characteristics. Compared to current mainstream methods, the accuracy of downstream clustering and node classification tasks can be improved by 0.5~41.8%, which significantly improves the quality of embedding, and it also has a shorter running time than most comparison algorithms.

Gastric cancer is a common type of cancer that poses a serious threat to human health. Polysaccharides are important functional phytochemicals, and research shows that polysaccharides have good anti-gastric cancer effects. We collated all relevant literature published from 2000 to 2020 and found that more than 60 natural polysaccharides demonstrate anti-gastric cancer activity. At the present, the sources of these polysaccharides include fungi, algae, tea, Astragalus membranaceus, Caulis Dendrobii, and other foods and Chinese herbal medicines. By regulating various signaling pathways, including the PI3K/AKT, MAPK, Fas/FasL, Wnt/β-catenin, IGF-IR, and TGF-β signaling pathways, polysaccharides induce gastric cancer cell apoptosis, cause cell cycle arrest, and inhibit migration and invasion. In addition, polysaccharides can enhance the immune system and killing activity of immune cells in gastric cancer patients and rats. This comprehensive review covers the extraction, purification, structural characterization, and mechanism of plant and fungal polysaccharides against gastric cancer. We hope this review is helpful for researchers to design, research, and develop plant and fungal polysaccharides.

Depression has become one of the severe mental disorders threatening global human health. In this study, we first used the proteomics approach to obtain the differentially expressed proteins in the liver between naive control and chronic social defeat stress (CSDS) induced depressed mice. We have identified the upregulation of iron binding protein transferrin (TF) in the liver, the peripheral blood, and the brain in CSDS-exposed mice. Furthermore, bioinformatics analysis of the Gene Expression Omnibus (GEO) database from various mouse models of depression revealed the significantly upregulated transcripts of TF and its receptor TfR1 in multiple brain regions in depressed mice. We also used the recombinant TF administration via the tail vein to detect its permeability through the blood-brain barrier (BBB). We demonstrated the permeability of peripheral TF into the brain through the BBB. Together, these results identified the elevated expression of TF and its receptor TfR1 in both peripheral liver and the central brain in CSDS-induced depressed mice, and peripheral administration of TF can be transported into the brain through the BBB. Therefore, our data provide a compelling information for understanding the potential role and mechanisms of the cross-talk between the liver and the brain in stress-induced depression.

Intestinal mucositis (IM) is the main side effect observed in patients who receive cancer chemotherapy. The characteristics of ulceration, vomiting, and severe diarrhea cause patients to delay or abandon further treatment, thereby aggravating their progress. Hence, IM cannot be overlooked. β-patchoulene (β-PAE) is an active ingredient isolated from Pogostemon cablin (Blanco) Benth (Labiatae) and has shown a marked protective effect against gastrointestinal diseases in previous studies. However, whether β-PAE plays a positive role in IM is still unknown. Herein, we explore the effects and the underlying mechanism of β-PAE against 5-fluorouracil (5-FU)-induced IM in IEC-6 cells and rats. β-PAE significantly recovered cell viability, upregulated the IM-induced rat body weight and food intake and improved the pathological diarrhea symptoms. Aquaporin is critical for regulating water fluid homeostasis, and its abnormal expression was associated with pathological diarrhea in IM. β-PAE displayed an outstanding effect in inhibiting aquaporin 3 (AQP3) via the cAMP/protein kinase A (PKA)/cAMP-response element-binding protein (CREB) signaling pathway. Besides, inflammation-induced mucus barrier injury deteriorated water transport and aggravated diarrhea in IM-induced rats. β-PAE’s effect on suppressing inflammation and recovering the mucus barrier strengthened its regulation of water transport and thus alleviated diarrhea in IM-induced rats. In sum, β-PAE improved IM in rats mainly by improving water transport and the mucus barrier, and these effects were correlated with its function on inhibiting the cAMP/PKA/CREB signaling pathway.

Human regulatory T (Treg) cells play a central role in controlling allergic inflammation in the airways. A reduced number of peripheral Treg cells and decreased suppressive function have been previously reported in the pathogenesis of allergic asthma. However, the characteristic role of specific Treg cell subsets and their mechanisms in the pathogenesis of allergic asthma remain unclear. In this study, we examined the proportion of different Treg cell subsets in both healthy subjects and patients with allergic asthma using flow cytometry and single-cell RNA sequencing. The migration function of the cells was compared using cell sorting and Transwell experiments. Furthermore, two allergen-challenged mouse models and a cell transfer experiment were used to examine the role of these Treg subsets. We found that the proportion of CD25+Foxp3+CD127- Treg cells in the peripheral blood of patients with allergic asthma was lower than in those of healthy subjects. Furthermore, the circulating Treg cells expressed lower levels of CCR6 and IL-17 compared with healthy subjects. The chemokine from the airway mucosa, CCL20, was abundantly expressed, and Transwell experiments further proved that this chemokine promoted CCR6+ Treg cell migration in vitro. A mouse model induced by house dust mite (HDM) revealed that the number of CCR6+ Treg cells in the lung tissue increased remarkably. The incidence of allergic asthma may be related to an increase in Treg cells secreting IL-17 in the lung tissue. Recruited CCR6+ Treg cells are likely to differentiate into Th17-like cells under the Th17 environment present in the lungs. IL-17 derived from Th17-like cells could be associated with the pathology of allergic asthma by promoting Th17 responses, thereby favoring HDM-induced asthma exacerbations.

Transforming growth factor-β (TGF-β) is composed of three isoforms, TGF-β1, TGF-β2, and TGF-β3. TGF-β1 is a cytokine with multiple biological functions that has been studied extensively. It plays an important role in regulating the differentiation of immune cells and maintaining immune cell functions and immune homeostasis. Pregnancy is a carefully regulated process. Controlled invasion of trophoblasts, precise coordination of immune cells and cytokines, and crosstalk between trophoblasts and immune cells play vital roles in the establishment and maintenance of normal pregnancy. In this systematic review, we summarize the role of TGF-β1 in regulating fetal-maternal immune tolerance in healthy and pathological pregnancies. During healthy pregnancy, TGF-β1 induces the production of regulatory T cells (Tregs), maintains the immunosuppressive function of Tregs, mediates the balance of M1/M2 macrophages, and regulates the function of NK cells, thus participating in maintaining fetal-maternal immune tolerance. In addition, some studies have shown that TGF-β1 is dysregulated in patients with recurrent spontaneous abortion or preeclampsia. TGF-β1 may play a role in the occurrence and development of these diseases and may be a potential target for the treatment of these diseases.

How plant competition varies with the changes of biotic and abiotic factors has been debated for a long time in the field of ecology. The aim of this study was to explore how neighbors and soil fertility influenced the intensity and importance of competition on species Stipa grandis and S. krylovii. We conducted a target species (S. grandis and S. krylovii) × soil fertility (low and high fertility) × competition treatment (4 treatments: two target species grown in monoculture and in mixture with each other, and in mixture with Leymus chinensis or Agropyron cristatum) microcosm experiment. We calculated the intensity (NIntA) and importance (NImpA) of neighbor-effect with additive symmetry for each target species under different treatments, and explored how the NIntA and NImpA were influenced by the target species, neighbor identity and soil fertility. We calculated the fertilizer-addition effect index on each target species to explore how neighbor identity influenced the index. (1) When target species in mixture with L. chinensis, both the NIntA and NImpA decreased with the increase of soil fertility. The NImpA was significantly negative on S. grandis under both soil fertility treatments and on S. krylovii under the high soil fertility treatment. (2) When target species in mixture with A. cristatum, the NIntA significantly influenced by the interaction between target species and soil fertility. The NImpA was significantly negative on S. grandis under the low soil fertility treatment and on S. krylovii under the high soil fertility treatment. (3) When in S. grandis – S. krylovii mixture system, the NIntA increased with the increase of soil fertility, and the NImpA showed no significant effects on each target species. (4) The fertilizer-addition effect was higher than zero for all treatments except the one on S. grandis in mixture with L. chinensis. The effect on S. krylovii was relatively lower than that on S. grandis in mixture with A. cristatum but was relatively higher in any of the other three competition treatments. The present findings demonstrated that the identities of both target and neighbor species influenced the fertilizer-addition effect and the responses of intensity and importance of competition to the changes of soil fertility. The present study showed the complexity of target species and neighbor identities in influencing the outcomes of plant competition, and provided novel insights into how plant competition driving the community dynamics in the context of soil fertility changes.

BackgroundInflammation-related gene polymorphisms are some of the most important determinants for cancer susceptibility, clinical phenotype diversity, and the response to radiotherapy and chemotherapy. However, the relationship between these polymorphisms and head and neck squamous cell carcinoma (HNSCC) remains unclear. The aim of this study was to investigate the role of inflammation-related gene polymorphisms in the developmental risk and radiotherapy sensitivity of HNSCC.MethodsThe Matrix-Assisted Laser Desorption Ionization Time of Flight (MALDI-TOF) genotyping system was used to genotype 612 individuals from a Chinese population for 28 inflammation-related gene polymorphisms.ResultsThe protein kinase B (AKT1) rs1130233 TT, dominance model (CT+TT vs. CC), recessive model (TT vs. CT+CC), and rs2494732 CC genotypes were associated with reduced risk of HNSCC (P=0.014; P=0.041; P=0.043). The polymeric immunoglobulin receptor (PIGR) rs291097 GA, dominance model (GA+AA vs. GG), and rs291102 dominance model (GA+AA vs. GG) were associated with increased risk of HNSCC (P=0.025; P=0.025; P=0.040). The interleukin-4 receptor-α (IL-4RA) rs1801275 AA genotype was significantly correlated with increased radiotherapy sensitivity of HNSCC patients (P=0.030). In addition, age ≤ 60 years, non-smoker status, and normal levels of squamous cell carcinoma antigen (SCC) were found to be associated with increased radiotherapy sensitivity of HNSCC patients (P=0.033; P=0.033; P=0.030).ConclusionThe AKT1 rs1130233, AKT1 rs2494732, PIGR rs291097, and PIGR rs291102 polymorphisms were significantly related to the risk of HNSCC. The IL-4RA rs1801275 polymorphism, age ≤ 60 years, non-smoker status, and normal levels of SCC were significantly associated with increased radiotherapy sensitivity of HNSCC.

This paper proposes a fractional order (FO) impedance model for lithium-ion batteries and a method for model parameter identification. The model is established based on electrochemical impedance spectroscopy (EIS). A new hybrid genetic–fractional beetle swarm optimization (HGA-FBSO) scheme is derived for parameter identification, which combines the advantages of genetic algorithms (GA) and beetle swarm optimization (BSO). The approach leads to an equivalent circuit model being able to describe accurately the dynamic behavior of the lithium-ion battery. Experimental results illustrate the effectiveness of the proposed method, yielding voltage estimation root-mean-squared error (RMSE) of 10.5 mV and mean absolute error (MAE) of 0.6058%. This corresponds to accuracy improvements of 32.26% and 7.89% for the RMSE, and 43.83% and 13.67% for the MAE, when comparing the results of the new approach to those obtained with the GA and the FBSO methods, respectively.

A new control strategy is proposed to suppress earthquake-induced vibrations on uncertain building structures. The control strategy embeds fuzzy logic in a fractional-order (FO) proportional derivative (FOPD) controller. A new improved FO particle swarm optimization (IFOPSO) algorithm is derived to adjust the initial parameters of the FOPD controller. An original fuzzy logic-FOPD (FFOPD) controller is then designed by combining the advantages of the fuzzy logic and FOPD control, to deal with large displacements on structures under earthquake excitation. Simulation experiments are carried out on uncertain building structures subjected to the effects of different kinds of seismic signals, illustrating the validity and feasibility of the proposed method.

The spatial distribution of droplet size and velocity affects the deposition and distribution on the target. In order to investigate the influence of different adjuvant and pressures on the spatial distribution of droplet size and velocity in atomization area of different nozzles, air induction flat fan nozzle IDK120-03, multi-range flat fan nozzle LU120-03 and anti-drift flat fan nozzle AD120-03 were selected. Phase Doppler Interferometer (PDI) was used to analyze and compare the distribution of droplet size and velocity in the atomization area of three nozzles when four typical adjuvant Maisi, Maidao, Adsee AB-600 and Surun sprayed at different pressures. The results show that the volume median diameter of droplet size has no obvious change along the vertical direction of the nozzle center and increases with distance in the horizontal direction, the droplet size decreases with increasing pressure at the same position, the adjuvant all increases the droplet size (about 12%, 12%, 10% and 9% for Maisi, Maidao, Surun and Adsee AB-600, respectively), IDK120-03 nozzle droplet size is the largest and LU120-03 nozzle is the smallest in the same position. For droplet velocity distribution, droplet velocity decrease in distance along the vertical and horizontal direction, respectively, the droplet velocity increases with increasing pressure at the same position, compared with water, the droplet velocity increased by about 13%, 9%, 8%, and 4% for Maisi, Maidao, Surun, and Adsee AB-600, respectively, the velocity of AD nozzle is the largest and IDK nozzle is the smallest at the same position. The experiment can provide a basis for the selection of adjuvants and nozzles in pesticide application, and provide a data base for studying the distribution of droplets on the target.

The trajectory planning method with dynamics is the key to improving the motion performance of manipulators. The optimal control method (OCM) is a key technology to solve optimal problems with dynamics. There are direct and indirect methods in OCM; indirect methods are difficult to apply to engineering applications, and so direct methods are widely applied instead. The direct collocation method (DCM) is a technology in OCM to transform an optimal control problem (OCP) to a nonlinear problem (NLP), so that plenty of solvers can be used directly. However, the general DCM, for which it has been found that the explicit form of the right-hand-side (RHS) functions of state equations of the complex system in the OCP is hard to derive, is limited to solving the OCP of three-axis manipulators. This paper proposes an improved DCM to solve the OCP of six-axis manipulators, which can find the solution of the time-optimal trajectory for the motion of six-axis manipulators based on the improved DCM. The proposed method derives the RHS equations implicitly by introducing a Functional Mock-up Unit (FMU), which simplifies the representation of the RHS equations as a black-box model, so that the DCM can be applied to the OCP of six-axis manipulators. A simulation case of a three-axis manipulator accomplished in a related study works as a reference compared with our improved method to verify the solution consistence between the DCM using the explicit RHS equations or using the implicit RHS equations, and the loss of computational efficiency is acceptable. In the meantime, a simulation solution and an experiment of six-axis manipulators, which is a novel advancement, are presented to validate the proposed method.

Fractional calculus (FC) generalizes the concepts of derivative and integral to non-integer orders [...]

The plume-surface interaction that occurs as a result of a variable-thrust engine exhaust plume impinging on soil during landings is critical for future lunar mission design. Unique lunar environmental properties, such as low gravity, high vacuum, and the regolith layer, make this study complex and challenging. In this paper, we build a reliable simulation model, with constraints based on landing photos, to characterize the erosion properties induced by a low-thrust engine plume. We focus on the low-thrust plume-surface erosion process and erosion properties during the Chang’E-5 mission, aiming to determine the erosion difference between high- and low-thrust conditions; this is a major concern, as the erosion process for a low-thrust lunar mission is rarely studied. First, to identify the entire erosion process and its relative effect on the flat lunar surface, a one-to-one rocket nozzle simulation model is built; ground experimental results are utilized to verify the simulated inlet parameters of the vacuum plume flow field. Following that, plume flow is considered using the finite volume method, and the Roberts erosion model, based on excess shear stress, is adopted to describe plume-surface interaction properties. Finally, a Lagrangian framework using the discrete phase model is selected to investigate the dynamic properties of lunar dust particles. Results show that erosion depth, total ejected mass, and the maximum particle incline angle during the Chang’E-5 landing period are approximately 0.2 cm, 335.95 kg, and 4.16°, respectively. These results are not only useful for the Chang’E-5 lunar sample analysis, but also for future lunar mission design.

To improve the consistency of sectional gas velocities in different rows in the pneumatic conveying line for a paddy side-deep fertilisation system, a new airflow equaliser was designed based on the mechanism of gas flow in ventilation engineering. Subsequently, the effects of key structural parameters and a position parameter of the airflow equaliser on the consistency of sectional gas velocities in different rows were investigated using the method of single-factor tests in Fluent, which provided a reasonable range for the next orthogonal test (notch angle (A): 120–180°, extended length (B): 18–30 mm and distance between adjacent branches (C): 120–160 mm). Thereafter, the parameters were optimised through an orthogonal test, using the coefficient of variation of the consistency of the sectional gas velocities in different rows (CV) as an indicator and using Fluent software. The results revealed that the order of primary and secondary factors was evaluated as B > A × B > C > A, and when A, B and C were selected as 150°, 30 mm and 120 mm, respectively, the consistency of the sectional gas velocities in different rows could get a very effective result (CV = 7.07%). Finally, to validate the feasibility of simulations of the performance of the airflow equalisers and to practically evaluate the contribution of the optimised airflow equalisers to improve the consistency of the sectional gas velocities in different rows, a bench test for the line with the optimised airflow equalisers and a simulation test for the line without the optimised airflow equalisers were carried out and the results showed that the CV values were 9.53%, 20.69%, respectively. It concluded that the optimised airflow equalisers could significantly improve the consistency of the sectional gas velocities in different rows by comparing the CV in the three tests including the simulation test for the line with the optimised airflow equalisers. This research provides a good reference for optimising the pneumatic conveying line for a paddy side-deep fertilisation system.

Due to the cutting mechanism of the existing grafting machine, it cannot adjust the cutting angle in real time, resulting in low fitting precision on the cutting surfaces between the rootstocks and scion seedlings and, thus, seriously affecting the survival rate and quality of the grafting seedlings. In this paper, a kind of splice grafting method based on visual image is proposed, aiming at maximizing the joint rate between cutting surfaces of rootstocks and scion seedlings and realizing precise cutting and grafting of grafting machine. After analysis, we determined that melon rootstock seedlings have a structure of pith cavity inside, and the solid structure from the top of the pith cavity to the left and right base points of a growing point forms the important area of a cutting surface. In order to obtain the geometric model of the cutting surfaces of the seedlings, a visual image analysis system was established to identify, analyze, and model the pith cavity structure inside the rootstock seedling, as well as the external morphological characteristics, and the ultimate cutting angle of the rootstock seedling and cutting surface parameters were determined. By measuring the length of minor axis of scion seedlings in order to achieve the maximum joint rate, the optimal cutting angle of the rootstocks and scion seedlings was determined. Then grafting and seedling cultivation tests were carried out. The test results showed that the range of ultimate cutting angle on rootstock seedlings (Cucurbita moschata) was 18.21 ± 1.92°; the cutting angles of the rootstock (Cucurbita moschata) and scion seedlings (watermelon) were 22° and 19.68°, respectively; the cutting surface length of the two was 4.96 mm; and the cutting surface thickness of the rootstock was 0.13 mm, all of which could satisfy the technological requirements of the matched splice grafting of melons. The research results can serve as a reference for the design in vision-guided precision cutting and real-time grafting operation on grafting robots.

Ulcerative colitis (UC) is a chronic intestinal disease with unclear pathogenesis. With an increasing global prevalence over the past two decades, UC poses a serious threat to public health. Baitouweng decoction (BTW), a traditional Chinese medicine, has been shown to have good clinical efficacy for treating intestinal inflammation. Yet, the efficacy of BTW in UC and the underlying mechanism remain unclear. The current study aimed to determine whether BTW suppressed intestinal inflammation in mice and the potential mechanism. We used a dextran sulfate sodium (DSS)-induced murine colitis model to test the anti-inflammatory efficacy of BTW. Clinical symptoms were scored by the disease activity index (DAI), and the colon length and pathological changes in colon tissue were also used to further evaluate the efficacy of BTW. Precisely how BTW affected immune function and the intestinal barrier of UC mice was also examined. BTW significantly reduced DAI score and colonic pathological damage. BTW regulated the balance between T helper (Th)17 and regulatory T (Treg) cells, decreased interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, and increased IL-10 levels. BTW reduced intestinal permeability of UC mice, increased expression of tight junction proteins (occludin and zonula occludens-1), and decreased expression of phospho-nuclear factor (p-NF)-κB and phospho-extracellular signal-regulated kinase (p-ERK) in the colon. BTW inhibited the ERK/p-NF-κB signaling pathway and suppressed expression of cyclo-oxygenase-2 and inducible NO synthase in lipopolysaccharide-activated RAW 264.7 cells. BTW significantly promoted the synthesis of short-chain fatty acids in the gut, particularly acetate, propionate, isobutyric acid, and isovalerate. The results suggest that BTW can protect against DSS-induced UC. The mechanism may be partially attributed to regulating the balance of Th17/Treg cells and restoring the intestinal epithelial barrier.

BackgroundDiabetes and cancer are both multifactorial diseases, and epidemiologic evidence indicates that diabetes may be associated with the incidence of certain types of cancer. In diabetes the risk of pancreatic cancer is increased significantly. However, whether certain diabetes treatment being related with the risk of pancreatic cancer remains unclear. In this report, we presented a case of pancreatic ductal adenocarcinoma in a diabetic patient in China after being treated with liraglutide, a novel glucagon-like peptide-1 (GLP-1) analog.Case reportA 71-year-old Han Chinese man who had had a type 2 diabetes for 25 years presented at the endocrinology department with discomfort in the left upper quadrant of abdomen for 10 days. The patient’s vital signs and laboratory findings were unremarkable except for the elevated level of carbohydrate antigen (CA19-9). The upper abdomen routine enhanced computed tomography (CT) scan showed low density of the pancreatic body and tail, and the histopathological result of the pancreatic biopsy samples was pancreatic ductal adenocarcinoma with regional lymph node metastasis. We reviewed his former medical records and found that liraglutide was added to his hypoglycemic treatment regimen 20 months ago. At that time, the level of tumor biomarkers and upper abdomen routine CT were unremarkable. We estimated the causality between liraglutide and pancreatic cancer by the Naranjo Adverse Drug Reaction Probability scale and WHO-Uppsala Monitoring Centre (WHO-UMC) system, and the causality turned out to be possible.ConclusionOur report suggests that liraglutide may be related with the genesis and development of pancreatic cancer and also highlights the importance of regular checkups in diabetic patients treated with liraglutide. However, our report has some notable limitations, and further longer-term follow-up trials with larger sample should be conducted in future to assess the causality between liraglutide and pancreatic cancer.

Objective: This study aimed to evaluate the television (TV) viewing and computer and mobile phone usage duration in a community sample of Chinese adults and examine their associations with BMI and obesity.Methods: We conducted a community-based health needs assessment study from February to December 2018 among 2,873 Chinese adults in Nanshan District of Shenzhen, China. We used self-administered questionnaires to collect the data from 24 community health service centers in Nanshan District. The participants individually recorded the time they spent watching TV and using computers and mobile phones. They also answered questions about their sociodemographic and lifestyle factors. We measured their height and weight by using ultrasonic height and weight scales. Then, we calculated and categorized their BMI in accordance with the standards prescribed by the World Health Organization for Asians.Results: Most of the participants were young adults (aged 18–44 years, 74.2%). The overall prevalence of obesity was 15.30%. The prevalence of TV, computer, and mobile phone usage was 75.5, 71.2, and 93.8% in females and 71.1, 75.7, and 94.2% in males, respectively. The youth (18–24 years) and the elderly (65 years or older) had the longest time using mobile phones (3.78 ± 2.51 h) and watching TV programs (2.12 ± 1.38 h), respectively. Longer usage of computers and mobile phones was evident in males (p < 0.05) and participants with a high education level (p < 0.01). The univariate analysis results showed an association between high BMI and obesity and short duration of using computers and mobile phones (all p < 0.05). By contrast, no significant associations were found between the length of TV program viewing and mobile phone usage and BMI (p > 0.05). After we adjusted for potential confounders, we found that computer usage time and the overall usage time of the three electronic devices had an inverse association with BMI (p < 0.05).Conclusions: Mobile phones were the most popular electronic device in Nanshan residents of Shenzhen. Unlike most previous studies, we found an inverse association between screen time and BMI. Nevertheless, scholars should conduct further studies to explore this association. Overall, we strongly encourage the appropriate use of electronic devices.

The dilatancy behavior of rockfill materials shows obvious stress path dependence. Lade-Kim plastic potential equation has been proposed for a long time to model the mechanical behavior of sand and concrete materials. However, it lacks the verification of rockfill materials, especially under various stress paths. In this paper, the dilatancy performance of coarse-grained materials under various stress paths is investigated, and then the dilatancy equation description and verification method based on Lade-Kim plastic potential are given. The applicability of Lade-Kim plastic potential for different stress path tests, such as conventional triaxial tests, constant P tests, and constant stress (increment) ratio tests, are verified and evaluated. It is found that Lade-Kim plastic potential is difficult to consider the influence of stress path. Finally, the Lade-Kim plastic potential, together with nonlinear dilatancy equation, is evaluated by changing the dilatancy equation in the framework of generalized plasticity. Lade-Kim plastic potential is suitable for constant stress increment ratio loading experiments and special care should be taken when applied to other stress paths. These works are helpful to understand stress path dependence of dilatancy behavior for rockfill materials and is beneficial for the establishment of stress path constitutive model.

The classical classifiers are ineffective in dealing with the problem of imbalanced big dataset classification. Resampling the datasets and balancing samples distribution before training the classifier is one of the most popular approaches to resolve this problem. An effective and simple hybrid sampling method based on data partition (HSDP) is proposed in this paper. First, all the data samples are partitioned into different data regions. Then, the data samples in the noise minority samples region are removed and the samples in the boundary minority samples region are selected as oversampling seeds to generate the synthetic samples. Finally, a weighted oversampling process is conducted considering the generation of synthetic samples in the same cluster of the oversampling seed. The weight of each selected minority class sample is computed by the ratio between the proportion of majority class in the neighbors of this selected sample and the sum of all these proportions. Generation of synthetic samples in the same cluster of the oversampling seed guarantees new synthetic samples located inside the minority class area. Experiments conducted on eight datasets show that the proposed method, HSDP, is better than or comparable with the typical sampling methods for F-measure and G-mean.

Background: 5-fluorouracil (5-FU) is a widely used drug for cancer treatment, but its effect and underlying mechanisms on osteosarcoma (OS) cells remain unclear. Methods: U2OS and MG63 cells were treated with 0, 50, 100, and 500 μM 5-FU. MTS and flow cytometry were used to examine the effect of 5-FU on cell viability and apoptosis, respectively. Circular RNA (circRNA) expression was detected using RNA sequencing and quantitative real-time PCR (qPCR). Differentially expressed circRNAs were further subjected to the Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) analysis to predict their functions. A circRNA–miRNA–mRNA interaction network was generated to analyze the regulatory networks of 5-FU–induced differentially expressed circRNAs. Western blotting (WB) was used to verify the protein in the downstream of circRNAs. Results: 5-FU inhibited the cell viability of the MG63 cells in a concentration-dependent manner. The most significant effect was observed in the cells treated with 500 μM 5-FU. Apoptosis was also increased in the MG63 cells after 500 μM 5-FU treatment for 3 days. RNA sequencing results showed that 183 differentially expressed circRNAs (172 upregulated and 11 downregulated) in 5-FU–treated cells. KEGG and GO analysis showed that the differentially expressed circRNAs were primarily enriched in proliferation-, apoptosis-, and metabolism-related functions. qPCR was used to verify the most upregulated and downregulated circRNAs. The circRNA–miRNA–mRNA interaction network showed that these 8 circRNAs had a sizable regulatory network that links a series of genes involved in tumor suppression. Conclusion: 5-FU treatment resulted in the differentially expressed circRNAs that were proliferation- and apoptosis-associated and were involved in the 5-FU–induced inhibition of tumor proliferation in OS cells.

Objectives: As of June 1, 2020, coronavirus disease 2019 (COVID-19) has caused a global pandemic and resulted in over 370,000 deaths worldwide. Early identification of COVID-19 patients who need to be admitted to the intensive care unit (ICU) helps to improve the outcomes. We aim to investigate whether absolute eosinophil count (AEC) can predict ICU transfer among elderly COVID-19 patients from general isolation wards.Methods: A retrospective study of 94 elderly patients older than 60 years old with COVID-19 was conducted. We compared the basic clinical characteristics and levels of inflammation markers on admission to general isolation wards and the needs for ICU transfer between the eosinopenia (AEC on admission

High mobility group box 1 (HMGB1) is a ubiquitous nuclear protein in mammals. When released into the extracellular space, it acts as a damage-associated molecular pattern. This study investigates whether increased HMGB1 levels are found in the intestinal mucosa of ulcerative colitis (UC) patients, and whether an anti-HMGB1 neutralizing-antibody (HnAb) can inhibit the intestinal inflammation elicited by dextran sulfate sodium (DSS) in mice. Because toll-like receptor 4 (TLR4) is implicated in HMGB1-mediated immune cell activation, DSS colitis was also elicited in TLR4-deficient mice in the presence and absence of HnAb. The expression of HMGB1 in UC patients was examined. HnAb was administered via intraperitoneal injection to TLR4 deficient mice and their wild-type littermates, both being induced to colitis with DSS. Finally, the protective effect of HnAb and TLR4 deficiency were evaluated. In UC patients, HMGB1 was up-regulated in the inflamed colon. When administered during DSS application, HnAb alleviated the severity of colitis with a lower disease activity index, limited histological damages, and reduced production of proinflammatory cytokines. This antibody also limited colonic barrier loss, decreased colonic lamina propria macrophages and partially reversed the DSS treatment-associated dysbiosis. The protective effect of this antibody was enhanced in TLR4-deficient mice in some aspects, indicating that both additional HMGB1-mediated as well as TLR4-mediated inflammatory signaling pathways were involved in the induction of colitis by DSS. HnAb ameliorated colitis via macrophages inhibition and colonic barrier protection. It may therefore be a novel treatment option in colitis.

The massive production and activation of myofibroblasts (MFB) is key to the development of liver fibrosis. In many studies, it has been proven that hepatocytes are an important part of MFB, and can be transformed into MFB through epithelial-mesenchymal transition (EMT) during hepatic fibrogenesis. In our previous study, we confirmed that curcumin inhibited EMT procession and differentiation of hepatocytes into MFB. In addition, in previous studies, it has been shown that autophagy plays an important role in the regulation of cellular EMT procession. In the current study, we showed that curcumin inhibited TGF-β/Smad signaling transmission by activating autophagy, thereby inhibiting EMT. The mechanism of degradative polyubiquitylation of Smad2 and Smad3 is likely through inhibiting tetratricopeptide repeat domain 3 (TTC3) and by inducing ubiquitylation and proteasomal degradation of Smad ubiquitination regulatory factor 2 (SMURF2), which on account of the increase of autophagy in hepatocytes. Curcumin inhibits levels of reactive oxygen species (ROS) and oxidative stress in hepatocytes by activating PPAR-α, and regulates upstream signaling pathways of autophagy AMPK and PI3K/AKT/mTOR, leading to an increase of the autophagic flow in hepatocytes. In this study, we confirm that curcumin effectively reduced the occurrence of EMT in hepatocytes and inhibited production of the extracellular matrix (ECM) by activating autophagy, which provides a potential novel therapeutic strategy for hepatic fibrosis.

Background: Haploinsufficiency A20 (HA20) is a newly described monogenic disease characterized by a wide spectrum of manifestations and caused by heterozygous mutations in TNFAIP3 which encodes A20 protein. TNFAIP3 mutation leads to disruption of the A20 ovarian tumor (OTU) domain and/or the zinc finger (ZnF) domain. This study aims at exploring the association between the various manifestations of HA20 and different domains disruption of A20.Methods: We reviewed the HA20 cases in previous literature and summarized the clinical features, TNFAIP3 mutation loci and the disrupted domains caused by different sites and patterns of mutations. Patients were classified into three groups according to the A20 domains disruption.Results: A total of 89 patients from 39 families with a genetic diagnosis of HA20 were included. Overall, the age at onset of HA20 was early (median:5.92, IQR:1-10). Patients in the ZnF group showed the earliest onset (median:2.5, IQR:0.6-5), followed by patients in the OTU+ZnF group (median:6, IQR:1-10) and patients in the OTU group (median:10, IQR:8-14). The main manifestations of HA20 patients were recurrent oral ulcers (70%), recurrent fever (42%), gastrointestinal ulcers (40%), skin lesion (38%), genital ulcers (36%), and musculoskeletal disorders (34%). The percentage of patients with musculoskeletal disorders was significantly different among the three groups (p = 0.005). Patients in the OTU+ZnF group and ZnF group were more likely to develop musculoskeletal disorders than patients in the OTU group (p = 0.002 and p = 0.035, respectively). Besides, forty-three percent of HA20 patients were initially diagnosed as Behcet's disease (BD). Compared to the ZnF group, the OTU+ZnF group and OTU group had a higher percentage of patients initially diagnosed as BD (p = 0.006 and p < 0.001, respectively).Conclusion: HA20 is characterized by early-onset and the most common symptoms of HA20 are recurrent oral ulcers, fever and gastrointestinal ulcers. The onset of HA20 in patients with the ZnF domain disruption is earlier than patients with the OTU domain disruption. Compared to the OTU domain, the ZnF domain may be more closely related to musculoskeletal disorders.

Pyruvate kinase M2 (PKM2) is a key enzyme of glycolysis, which is highly expressed in many tumor cells, and has emerged as an important player in tumor progression and metastasis. However, the functional roles of PKM2 in tumor metastasis remain elusive. Here we showed that PKM2 promoted prostate cancer metastasis via extracellular-regulated protein kinase (ERK)–cyclooxygenase (COX-2) signaling. Based on public databases, we found that PKM2 expression was upregulated in prostate cancer and positively associated with tumor metastasis. Further analysis showed that PKM2 promoted prostate cancer cell migration/invasion and epithelial–mesenchymal transition (EMT) through upregulation of COX-2. Mechanistically, PKM2 interacted with ERK1/2 and regulated its phosphorylation, leading to phosphorylation of transcription factor c-Jun, downstream of ERK1/2, to activate COX-2 transcription by IP and ChIP assay, while inhibition of COX-2 significantly reversed the promotion effect of PKM2 on tumor metastasis in vivo. Taken together, our results suggest that a novel of PKM2–ERK1/2–c-Jun–COX-2 axis is a potential target in controlling prostate cancer metastasis.

The aim of this study is to investigate the role of microRNA-499 (miR-499) in hepatocellular carcinoma tumor growth and the underlying molecular mechanisms. The expression of miR-499 was significantly decreased in hepatocellular carcinoma tissues compared with that in adjacent normal tissues. Furthermore, miR-499 overexpression in HEPG2 cell was related to the tumor growth in nude mice xenograft models. Likewise, miR-499 mimic or inhibitor decreased or accelerated cell proliferation, respectively. Mechanistically, miR-499 directly targeted the 3′- untranslated region of astrocyte elevated gene-1 and downregulate astrocyte elevated gene-1 expression. Restoration of astrocyte elevated gene-1 expression in hepatocellular carcinoma cells reversed the inhibitory effect of miR-499 on cell growth. In addition, astrocyte elevated gene-1 and miR-499 expression were inversely correlated in human and mice hepatocellular carcinoma tissues. Our study identified miR-499 as a tumor-suppressive miR in hepatocellular carcinoma, thus providing a candidate therapeutic target for the future diagnosis or treatment of hepatocellular carcinoma.

The pathogenesis of preeclampsia (PE) involves several pathophysiological processes that may be affected by glucocorticoid (GC). We confirmed previously that GC exposure could result in PE, while PE is linked to a deficiency of lipoxin A4 (LXA4), an endogenous dual anti-inflammatory and proresolving mediator. The present study was to investigate whether GC exposure induces PE via dampening LXA4. In the study, cortisol levels of PE women were higher than those of normal pregnancies, LXA4 levels were downregulated in both PE patients and GC-mediated PE rats, and leukotriene B4 (LTB4) levels were upregulated in both PE patients and GC- mediated PE rats. Moreover, cortisol levels were negatively correlated to LXA4 levels, while positively correlated to LTB4 levels in PE patients. Mechanically, GC downregulated LXA4via disturbing its biosynthetic enzymes, including ALOX15, ALOX5B and ALOX5, especially activating ALOX5, the key enzyme for class switching between LXA4 and LTB4. Importantly, replenishing LXA4 could ameliorate PE-related symptoms and placental oxidative stress in PE rat model induced by GC. Moreover, LXA4 could inhibit GC-mediated ALOX5 activation and LTB4 increase, and also suppress 11β-HSD2 expression and corticosterone upregulation. The protective actions of LXA4 might be explained by its roles in antagonizing the adverse effects of GC on trophoblast development. Together, our findings indicate that GC exposure could contribute to PE through dampening LXA4, and GC/LXA4 axis may represent a common pathway through which PE occurs.

The determination of PM2.5-induced biological response is essential for understanding the adverse health risk associated with PM2.5 exposure. In this study, we conducted cell-based bioassays to measure the toxic effects of PM2.5 exposure, including cytotoxicity, oxidative stress, genotoxicity and inflammatory response. The concentration-response relationship was analyzed by benchmark dose (BMD) modeling and the BMDL10 was used to estimate the biological potency of PM2.5 exposure. PM2.5 samples were collected from three typical megacities of China (Beijing, BJ; Wuhan, WH; Guangzhou, GZ) in typical seasons (winter and summer). The total PM, water-soluble fractions (WSF), and organic extracts (OE) were prepared and subjected to examination of toxic effects. The biological potencies for cytotoxicity, oxidative stress and genotoxicity were generally higher in winter samples, while the inflammatory potency of PM2.5 was higher in summer samples. The relative health risk (RHR) was determined by integration of the biological potencies and the cumulative exposure level, and the ranks of RHR were BJ-W > WH-W > BJ-S > WH-S > GZ-W > GZ-S. Notably, we note that different PM2.5 compositions were associated with distinct biological effects, and the health effects distribution of PM2.5 varied in regions and seasons. These findings demonstrate that the approach of integrated cell-based bioassays could be used for the evaluation of health effects of PM2.5 exposure.

Abstract Background The epidemiological characteristics of sudden cardiac death (SCD) in the autonomous region of Xinjiang Uygur have been largely unknown. This study aimed to evaluate the incidence and demographic risk factors of SCD in Xinjiang, China. Methods This retrospective study reviewed medical records from 11 regions in Xinjiang with different geography (north and south of the Tian Shan mountain range), gross domestic product, and ethnicity (Han, Uyghur, Kazakh, and Hui). SCD was defined as unexpected death due to cardiac reasons within 1 hour after the onset of acute symptoms, including sudden death, unexpected death, and nonviolent death. Monitoring was conducted throughout 2015. Demographic and mortality data were recorded and age-adjusted standardized risk ratio (SRR) was analyzed. Results Among 3,224,103 residents, there were 13,308 all-cause deaths and 1244 events of SCD (784 men and 460 women; overall incidence 38.6 per 100,000 residents). SCD was associated with age (χ2 = 2105.3), but not geography. Men had an increased risk of SCD compared with women (SRR: 1.75, 95% CI: 1.10–2.79). The risk of SCD was highest in residents of the Uyghur (SRR: 1.59, 95% CI: 1.05–2.42) and Kazakh (SRR: 1.92, 95% CI: 1.29–2.87) compared with those of the Han. Poor economic development was associated with elevated risk of SCD (SRR: 1.55, 95% CI: 1.02–2.38). Conclusion SCD is an important public health issue in China. Our understanding of the demographic differences on SCD in Xinjiang, China may improve the risk stratification and management to reduce the incidence and lethality of SCD.

Monitoring and mapping forest carbon is critical for informing climate change mitigation measures. Evidence indicates that forest edges hold less carbon than the forest interior. In this study, using field inventory data from a Chinese fir forest ecosystem in southeast China, the carbon at the forest edge and forest interior at different elevations was measured. The results showed a significant increasing trend in carbon with elevation. The results also revealed that forest edges had significantly lower carbon than the forest interior. Carbon density values varied between 265 Mg C ha−1 at forest edges and 320 Mg C ha−1 at forest interior. The study highlights that ignoring edge effects overestimates carbon density by 9.46%. These findings suggest that edge effects should be given proper consideration during national forest carbon inventory. Furthermore, the authors recommend the establishment of permanent sampling plots along forest edges for precise and accurate carbon accounting.

It is generally accepted that exposure to particulate matter (PM) increases the risk of cardiovascular-related morbidity and mortality, though the exact mechanism behind this has yet to be elucidated. Oxidative stress plays a potentially important role in the mechanism of toxicity, with Nrf2 serving as a major antioxidant gene. In the current study, a Nrf2 knockout mouse model was used in combination with an individual ventilated cage (IVC)-based real-ambient PM exposure system to assess the potential cardiotoxicity induced by real-ambient PM exposure and the potential role of Nrf2 and related signaling in this endpoint. After 6- or 11-weeks exposure to PM, ICP-mass spectrometry was used to assess the metal depositions in the heart tissue following PM exposure. Functional and morphological changes in the hearts were investigated with echocardiography and histopathology, and oxidative stress levels were assessed with a serum malondialdehyde content assay. In the further mechanistic study, an RNA-seq technique was utilized to assess the gene transcription status in the hearts of C57/B6 mice exposed to PM with or without Nrf2 knockout. The expression levels of genes of interest were then further investigated with quantitative real-time PCR and western blotting. The results indicated that PM exposure resulted in significant elevation of sodium, potassium, selenium, and ferrum levels in mouse heart tissue. Meanwhile, significantly altered heart function and morphology were observed. Interestingly, Nrf2 knockout led to abolishment of PM-induced effects in several functional parameters but not the morphological changes. Meanwhile, elevated malondialdehyde content was observed in Nrf2 knockout animals. RNA-seq results revealed thousands of genes altered by PM exposure and/or Nrf2 knockout, and this affected several pathways, such as MAPK, phagosome, calcium signaling, and JAK-STAT. In subsequent molecular studies, enhanced nuclear translocation of Nrf2 was also observed following PM exposure, while the MAPK signaling pathway along with related JAK-STAT and TGF-β1 pathway genes, such as p38MAPK, AKT, TAK1, JAK1, STAT3, GRB2, TGFb1, and SMAD2, were confirmed to be affected by PM exposure and/or Nrf2 knockout. The data suggested that PM may induce cardiotoxicity in C57/B6 mice in which Nrf2 plays both protective and detrimental roles involving cardiac-related pathways, such as MAPK, JAK-STAT, and TGF-β1.

The dynamics and synchronization of fractional-order (FO) chaotic systems have received much attention in recent years. However, the research are focused mostly on FO commensurate systems. This paper addresses the synchronization of incommensurate FO (IFO) chaotic systems. By employing the comparison principle for FO systems with multi-order and the linear feedback control method, a sufficient condition for ensuring the synchronization of IFO chaotic systems is developed in terms of linear matrix inequalities (LMIs). Such synchronization condition relies just on the system parameters, and is easily verify and implemented. Two typical FO chaotic systems, named the IFO Genesio-Tesi system and Hopfied neural networks are selected to demonstrate the effectiveness and feasibility of the proposed method.

Crop residue is an important component of farmland ecosystems, which is of great significance for increasing soil organic carbon, mitigating wind erosion and water erosion and conserving soil and water. Crop residue coverage (CRC) is an important parameter to characterize the number and distribution of crop residues, and also a key indicator of conservation tillage. In this study, the CRC of wheat was taken as the research object. Based on the high-resolution GF-1 satellite remote sensing imagery from China, decision tree (DT), gradient boosting decision tree (GBDT), random forest (RF), least absolute shrinkage and selection operator (LASSO), extreme gradient boosting regression (XGBR) and other machine learning algorithms were used to carry out the estimation of wheat CRC by remote sensing. In addition, the comparisons with sentinel-2 imagery data were also utilized to assess the potential of GF satellite data for CRC estimates. The results show the following: (1) Among the spectral indexes using shortwave infrared characteristic bands from sentinel-2 imagery, the dead fuel index (DFI) was the best for estimating wheat CRC, with an R2 of 0.54 and an RMSE of 10.26%. The ratio vegetation index (RVI) extracted from visible and near-infrared characteristic bands from GF-1 data performed the best, with an R2 of 0.46 and an RMSE of 11.39%. The spectral index extracted from GF-1 and sentinel-2 images had a significant response relationship with wheat residue coverage. (2) When only the characteristic bands from the visible and near-infrared spectral ranges were applied, the effects of the spatial resolution differences of different images on wheat CRC had to be taken into account. The estimations of wheat CRC with the high-resolution GF-1 data were significantly better than those with the Sentinel-2 data, and among multiple machine learning algorithms adopted to estimate wheat CRC, LASSO had the most stable capability, with an R2 of 0.46 and an RMSE of 11.4%. This indicates that GF-1 high-resolution satellite imagery without shortwave infrared bands has a good potential in applications of monitoring crop residue coverage for wheat, and the relevant technology and method can also provide a useful reference for CRC estimates of other crops.

Currently, the robustness of pest recognition algorithms based on sample augmentation with two-dimensional images is negatively affected by moth pests with different postures. Obtaining three-dimensional (3D) posture information of pests can provide information for 3D model deformation and generate training samples for deep learning models. In this study, an algorithm of the 3D posture information extraction method for Hyphantria cunea (Drury) based on monocular vision is proposed. Four images of every collected sample of H. cunea were taken at 90° intervals. The 3D pose information of the wings was extracted using boundary tracking, edge fitting, precise positioning and matching, and calculation. The 3D posture information of the torso was obtained by edge extraction and curve fitting. Finally, the 3D posture information of the wings and abdomen obtained by this method was compared with that obtained by Metrology-grade 3D scanner measurement. The results showed that the relative error of the wing angle was between 0.32% and 3.03%, the root mean square error was 1.9363, and the average relative error of the torso was 2.77%. The 3D posture information of H. cunea can provide important data support for sample augmentation and species identification of moth pests.

Background: Several studies have reported microRNAs (miRNAs) could regulate the placental development, though the role and mechanism of miRNAs in the development of non-diabetic macrosomia (NDFMS) remains unclear. Methods: To identify the aberrantly expressed key miRNAs in placenta of NDFMS, we employed a strategy consisting of initial screening with miRNA microarray and further validation with quantitative RT-PCR assay (qRT-PCR). In vitro cellular model and a mouse pregnancy model were used to delineate the functional effects of key miRNA on proliferation, invasion, and migration. Findings: miR-141-3p was identified as the key miRNA with expression level significantly higher in placentas of NDFMS compared with those from normal controls. Overexpressed miR-141-3p in HTR-8/SVneo cells contributed to increased cell proliferation, invasion, and migration. miR-141-3p inhibition in HTR-8/SVneo cells resulted in decreased cell proliferation and invasion. Significantly increased infant birth weight was observed in late pregnancy of C57BL/6J mice treated with miR-141-3p agomir. However, no significant difference was found in early pregnancy of C57BL/6J mice treated with miR-141-3p agomir. Interpretation: miR-141-3p could stimulate placental cell proliferation to participate in the occurrence and development of NDFMS. Keywords: Birth weight, Macrosomia, microRNAs, miR-141-3p, Placenta

The association of atopic dermatitis and chronic spontaneous urticaria with socioeconomic status has been little studied. The aim of this study was to investigate the prevalence of skin diseases and their association with socioeconomic status in adolescents in China. A cross-sectional study was conducted at Central South University, Changsha, China. All newly enrolled students underwent dermatological examination and completed a survey. Socioeconomic status was measured in terms of parental education level and income. Two-level logistic regression models were used. A total of 8,226 students consented to participate. On dermatological examination, moderate to severe acne (10.2%) had the highest prevalence, followed by chronic spontaneous urticaria (2.7%), atopic dermatitis (2.5%), and tinea (1.7%). Socioeconomic status was positively associated with the prevalence of chronic spontaneous urticaria (ptrend = 0.001) and atopic dermatitis (ptrend = 0.0094). Tinea was inversely associated with socioeconomic status (ptrend = 0.025). Higher parental socioeconomic status was associated with higher risk of atopic dermatitis and chronic spontaneous urticaria, but lower risk of tinea.

To evaluate the effects of various rotation systems on rice grain yield and N use efficiency, a paddy–upland cropping experiment (2013–2016) was conducted in southeastern China. The experiment was designed using six different rice––winter crop rotations: rice–fallow (RF), rice–wheat (RW), rice–potato with rice straw mulch (RP), rice–green manure (Chinese milk vetch; RC–G), rice–oilseed rape (RO), and rice–green manure crop (oilseed rape with fresh straw incorporated into soil at flowering; RO–G) and three N rates, N0 (0 kg N ha−1), N1 (142.5 kg N ha−1), and N2 (202.5 kg N ha−1). Average rice yields in the RF (5.93 t ha−1) rotation were significantly lower than those in the rotations with winter crops (7.20–7.48 t ha−1) under the N0 treatment, suggesting that incorporation of straw might be more effective for increasing soil N than winter fallow. The rice yield differences among the rotations varied by year with the N input. In general, the grain yields in the RP and RO–G rotations –were respectively 11.6–28.5% and 14.80–37.19% higher than those in the RF in plots with N applied. Increasing the N rate may have tended to minimize the average yield gap between the RF and the other rotations; the yield gaps were 18.55%, 4.14%, and 0.23% in N0, N1, and N2, respectively. However, the N recovery efficiency in the RF was significantly lower than that in other rotations, except for 2015 under both N1 and N2 rates, a finding that implies a large amount of chemical N loss. No significant differences in nitrogen agronomic efficiency (NAE) and physiological efficiency (NPE) were found between the rotations with legume (RC–G) and non–legume (RO and RW) winter crops, a result that may be due partly to straw incorporation. For this reason, we concluded that the return of straw could reduce differences in N use efficiency between rotations with and without legume crops. The degree of synchrony between the crop N demand and the N supply was evaluated by comparison of nitrogen balance degree (NBD) values. The NBD values in the RP and RW were significantly lower than those in the other rotations under both N1 and N2 rates. Thus, in view of the higher grain yield in the RP compared to the RW under the N1 rate, the RP rotation might be a promising practice with comparable grain yield and greater N use efficiency under reduced N input relative to the other rotations. The primary yield components of the RF and RP were identified as number of panicles m−2 and numbers of kernels panicle−1, respectively. The NAE and NPE were positively correlated with harvest index, possibly providing a useful indicator for evaluating N use efficiency. Keywords: Rice (Oryza sativa L.), Paddy–upland rotation, Nitrogen use efficiency, Winter crops

Abstract In this paper, we aim to study the asymptotic properties of internal estimator of nonparametric regression with independent and dependent data. Under some weak conditions, we present some results on asymptotic normality of the estimator. Our results extend some corresponding ones.

Abstract Background In late 2016, an uncommon recombinant NoV genotype called GII.P16-GII.2 caused a sharp increase in outbreaks of acute gastroenteritis in different countries of Asia and Europe, including China. However, we did not observe a drastic increase in sporadic norovirus cases in the winter of 2016 in Huzhou. Therefore, we investigate the prevalence and genetic diversity of NoVs in the sporadic acute gastroenteritis (AGE) cases from January 2016 to December 2017 in Huzhou City, Zhejiang, China. Methods From January 2016 to December 2017, a total of 1001 specimens collected from patients with AGE were screened for NoV by real-time RT-PCR. Partial sequences of the RNA-dependent RNA polymerase (RdRp) and capsid gene of the positive samples were amplified by RT-PCR and sequenced. Genotypes of NoV were confirmed by online NoV typing tool and phylogenetic analysis. Complete VP1 sequences of GII.P16-GII.2 strains detected in this study were further obtained and subjected into sequence analysis. Results In total, 204 (20.4%) specimens were identified as NoV-positive. GII genogroup accounted for most of the NoV-infected cases (98.0%, 200/204). NoV infection was found in all age groups tested (60 years), with the 5–15 year age group having the highest detection rate (17/49, 34.7%). Higher activity of NoV infection could be seen in winter-spring season. The predominant NoV genotypes have changed from GII.Pe-GII.4 Sydney2012 and GII.P17-GII.17 in 2016 to GII.P16-GII.2, GII.Pe-GII.4 Sydney2012 and GII.P17-GII.17 in 2017. Phylogenetic analyses revealed that 2016–2017 GII.P16-GII.2 strains were most closely related to Japan 2010–2012 cluster in VP1 region and no common mutations were found in the amino acids of the HBGA-binding sites and the predicted epitopes. Conclusions We report the emergence of GII.P16-GII.2 strains and characterize the molecular epidemiological patterns NoV infection between January 2016 and December 2017 in Huzhou. The predominant genotypes of NoV during our study period are diverse. VP1 amino acid sequences of 2016–2017 GII.P16-GII.2 strains remain static after one year of circulation.

Abstract Background The link between the protocadherin-19 (PCDH19) gene and epilepsy suggests that an unusual form of X-linked inheritance affects females but is transmitted through asymptomatic males. Individuals with epilepsy associated with mutations in the PCDH19 gene display generalized or focal seizures with or without fever sensitivity. The clinical manifestation of the condition ranges from mild to severe, resulting in intellectual disability and behavioural disturbance. In the present study, we assessed mutations in the PCDH19 gene and the clinical features of a group of Chinese patients with early infantile epileptic encephalopathy and aimed to provide further insight into the understanding of epilepsy and mental retardation limited to females (EFMR; MIM 300088). Case Presentation We described three variations in the PCDH19 gene in Chinese patients with epilepsy who developed generalized seizures occurring in clusters with or without triggering by fever. Candidate genes were screened for mutations that cause epilepsy and related paroxysmal or nervous system diseases in the coding exons and intron–exon boundaries using polymerase chain reaction (PCR) of genomic deoxyribonucleic acid (DNA) followed by sequencing. The variations were sequenced using next-generation sequencing technology and verified with first-generation sequencing. Exome sequencing of a multigene epilepsy panel revealed three mutations in the PCDH19 gene in a mosaic male and two unrelated females. These included a frameshift mutation c.1508_1509insT (p.Thr504HisfsTer19), a missense mutation c.1681C > T (p.Pro561Ser) and a nonsense mutation c.918C > G (p.Tyr306Ter). Of the three mutations in the PCDH19 gene associated with early infantile epileptic encephalopathy, the frameshift variation in a mosaic male is novel and de novo, the missense variation is de novo and is the second ever reported in females, and the nonsense variation was inherited from the paternal line and is the first example discovered in a female. Conclusions The results from our current study provide new insight into and perspectives for the molecular genetic link between epilepsy and PCDH19 alterations. Moreover, our new findings of the male mosaic variant broaden the spectrum of PCDH19-related epilepsy and provide a new understanding of this complex genetic disorder.

Since of the scale and the various shapes of down in the image, it is difficult for traditional image recognition method to correctly recognize the type of down image and get the required recognition accuracy, even for the Traditional Convolutional Neural Network (TCNN). To deal with the above problems, a Deep Convolutional Neural Network (DCNN) for down image classification is constructed, and a new weight initialization method is proposed. Firstly, the salient regions of a down image were cut from the image using the visual saliency model. Then, these salient regions of the image were used to train a sparse autoencoder and get a collection of convolutional filters, which accord with the statistical characteristics of dataset. At last, a DCNN with Inception module and its variants was constructed. To improve the recognition accuracy, the depth of the network is deepened. The experiment results indicate that the constructed DCNN increases the recognition accuracy by 2.7% compared to TCNN, when recognizing the down in the images. The convergence rate of the proposed DCNN with the new weight initialization method is improved by 25.5% compared to TCNN. Keywords: Deep convolutional neural network, Weight initialization, Sparse autoencoder, Visual saliency model, Image recognition

Strong non-resonant few-cycle laser pulses can be used to induce ultrafast phase-controllable currents along nanojunctions but the microscopic origin is unclear. Here, the authors present time-dependent quantum transport simulations that recover the experimental observations and offer an intuitive picture of the effect.

Rotary atomizers are mainly used in agricultural manned aircrafts. Atomization characteristics at high speeds have been studied, but methods to measure the atomization efficiency have not been elucidated. The atomization efficiency of rotary atomizers under high-speed airflow was investigated using an IEA-I high-speed wind tunnel experimental installation, AU5000 rotary atomizer, and a laser diffraction particle size analyzer. Accordingly, a model equation for atomization efficiency measurements was innovatively obtained. When the flow rate, fan blade angle of the atomizer, and wind speed were used as variables, the experimental results showed that the atomization efficiency mainly depended on the fan blade angle. When the fan blade angle was 35°, the atomization efficiency was optimal, regardless of wind speed. In contrast, when the fan blade angle of the atomizer was 65°, it exhibited the worst atomization efficiency, regardless of the wind speed. The experimental data from this study can provide guidance for aerial application in fixed-wing manned aircraft, such as the flow rate, and operating speed.

Aiming to solve the problems of poor performance and low stability in the automatic clip-feeding of a grafting machine, an automatic clip-feeding mechanism with a precise single-clip discharge mechanism was designed, and a clip-feeding performance test was carried out. Taking the grafting clip of the 2TJGQ-800 type of vegetable-grafting robot as the research object, the clamping-force analysis model of the grafting clip was constructed by ABUQUS finite-element analysis software, and the variation law of clamping force, steel wire diameter, and opening deformation, as well as the calculation equation of clamping force, were obtained. The grafting clip model was verified by mechanical test, and test results showed that the grafting clip with a steel wire diameter of 0.7 mm proved safe and reliable for grafted cucumber and watermelon seedlings; the grafting clip with steel wire diameter of 0.8 mm had a risk of producing injury to grafted cucumber and watermelon seedlings when clamping. The method of single-clip discharge in the inclined discharging slideway was put forward, and the components for clip discharge and clip pushing were designed. The critical thrust for sending out the grafting clip in the clip-feeding slideway was 0.603 N after analyzing the force status of the grafting clip in the clip-feeding slideway. Test results showed that the success rate of automatic clip-feeding reached 98.67% when inclination angle of row-discharging slideway was 50° and the thrust of clip-pushing cylinder (input air pressure of 0.4 MPa) was 8.04 N, which met the technical requirements of mechanical grafting. The inclination of the grafting clip and the damaged clip in the feeding slideway is the main reason for the failure of clip-feeding. The research results can provide theoretical and design references for the innovative research of the automatic clip-feeding mechanism of grafting robots.

The accuracy of the state-of-charge (SOC) estimation of lithium batteries affects the battery life, driving performance, and the safety of electric vehicles. This paper presents a SOC estimation method based on the fractional-order square-root unscented Kalman filter (FSR-UKF). Firstly, a fractional second-order Resistor-Capacitance (RC) circuit model of the lithium battery is derived. The accuracy of the parameterized model is verified, revealing its superiority over integer-order standard descriptions. Then, the FSR-UKF algorithm is developed, combining the advantages of the square-root unscented Kalman filter and the fractional calculus. The effectiveness of the proposed algorithm is proven under a variety of operational conditions in the perspective of the root-mean-squared error, which is shown to be below 1.0%. In addition, several experiments illustrate the performance of the FSR-UKF.

Language teachers cannot ignore the role of technology in young language learners' lives to engage and motivate them. Therefore, the current research investigated the mediating effect of students' learning and cognitive styles on the relationship between their emotions and situational motivation. 1089 respondents were selected from different colleges and universities, with different ages, genders, and levels. Four questionnaires (Cognitive Scale of the Human--Nature Relationship, Learners' Emotion Questionnaire, The Situational Motivation Scale, and Learning Style Questionnaire) were employed to collect the data. The researcher used Tencent QQ, a widely used communication platform in China, in conjunction with Wenjuanxing, an online survey tool, to distribute the questionnaire to all participants. The results showed that 54% of changes in students' situational motivation can be explained by interaction among their emotions, learning, and cognitive styles. In addition, it was revealed that less attention is paid to the mental and psychological aspects of students in technology-enhanced learning environments, and most educational environments do not have the necessary compatibility with the psychological characteristics of students. Implications are presented.