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Antimicrobial resistance has been an increasingly serious threat to global public health. Anti-virulence strategies are being developed to manage antibiotic resistance because they apply a lower selective pressure for antimicrobial-resistant pathogens than that created using traditional bactericides. We aimed to discover novel small molecules that can reduce the production of virulence factors in Pseudomonas aeruginosa and determine the mechanism of action underlying these effects. A clinical compound library was screened, and ostarine was identified as a potential anti-virulence agent. The effects of ostarine were studied via antimicrobial susceptibility testing, bacterial growth assays, pyocyanin quantitation assays, transcriptomic analysis, quorum sensing signal molecule quantification, and real-time PCR assays. Ostarine treatment significantly decreased the synthesis of pyocyanin without any bactericidal action. Besides, ostarine treatment did not affect the relative growth rate and cell morphology of bacteria. Treatment with ostarine interfered with quorum sensing by decreasing the transcription of genes associated with quorum sensing systems and the production of signalling molecules. The inhibition of ostarine on pyocyanin production and gene expression can be alleviated when signalling molecules were supplemented externally. Overall, ostarine may act as a novel anti-virulence agent that can attenuate P. aeruginosa pyocyanin by interfering with quorum sensing systems.

Extrachromosomal circular DNA (eccDNA) refers to a type of circular DNA that originate from but are likely independent of chromosomes. Due to technological advancements, eccDNAs have recently emerged as multifunctional molecules with numerous characteristics. The unique topological structure and genetic characteristics of eccDNAs shed new light on the monitoring, early diagnosis, treatment, and prediction of cancer. EccDNAs are commonly observed in both normal and cancer cells and function via different mechanisms in the stress response to exogenous and endogenous stimuli, aging, and carcinogenesis and in drug resistance during cancer treatment. The structural diversity of eccDNAs contributes to the function and numerical diversity of eccDNAs and thereby endows eccDNAs with powerful roles in evolution and in cancer initiation and progression by driving genetic plasticity and heterogeneity from extrachromosomal sites, which has been an ignored function in evolution in recent decades. EccDNAs show great potential in cancer, and we summarize the features, biogenesis, evaluated functions, functional mechanisms, related methods, and clinical utility of eccDNAs with a focus on their role in evolution and cancer.

Numerous antitumor drugs exhibited excellent anti-proliferation activities, discovered from natural products. Oridonin is isolated from a traditional Chinese medicine Isodon rubescens, and it exhibit various biological functions including anticancer, anti-inflammation, antibacterial, and so on. The anticancer mechanisms of oridonin include apoptosis, autophagy, cell cycle arrest, and so on. However, clinical research and application of oridonin has been hampered, due to the poor pharmaceutical property. So many studies on oridonin have been explored in the purpose of improve the pharmaceutical property, including investigation of the mechanism of action in depth and structural modification. In this review, we summarized oridonin and oridonin derivatives as potential anticancer agents, and detailed discussion on biological properties, mechanism of actions and potential for overcoming therapeutic resistance.

We herein report a new lanthanide metal-organic framework (MOF) that exhibits excellent chemical stability, especially in the aqueous solution over a wide pH range from 1 to 14. In contrast to many reported lanthanide MOFs, this Tb-based MOF emits cyan fluorescence inherited from the integrated AIE-active ligand, rather than Ln3+ ions. More remarkably, its fluorescence signal features a highly selective and sensitive “turn-off” response toward CrO42−, Cr2O72− and Fe3+ ions, highlighted with the low detection limits down to 68.18, 69.85 and 138.8 ppm, respectively. Thus, the exceptional structural stability and sensing performance render this material able to be a superior luminescent sensor for heavy metal ions in wastewater.

BackgroundGiant cell tumors of the mobile spine invasion of the adjacent vertebrae are an ignored imaging finding.MethodsNine patients with giant cell tumors of the mobile spine with invasion of the adjacent vertebrae confirmed by pathology were enrolled. Eight patients had pure giant cell tumors (GCTs), while one patient also had an aneurysmal bone cyst. All patients underwent conventional computed tomography, three-dimensional reconstruction, and conventional magnetic resonance imaging, while seven patients also underwent post-contrast magnetic resonance imaging.ResultsAll patients showed GCTs of the mobile spine that arose from the vertebral body and extended to the vertebral arch. The tumors showed soft-tissue attenuation with no evidence of a mineralized matrix. Pathological fracture was seen in five patients. The margin of the original tumor showed partial sclerosis in four patients and involved an adjacent vertebral body with a sclerotic rim in two patients. The tumors showed a homogeneous and similar signal intensity to the normal spinal cord on T1WI (T1-weighted image) in five patients. The cystic area of the tumors was hyperintense on T2WI in the remaining four patients, while one patient showed hemorrhage that was hyperintense on T1WI. The solid components of the GCTs show marked enhancement in all cases, while the cystic area of the tumors was observed without enhancement on contrast-enhanced images in four patients. Bone destruction of the adjacent vertebral body showed a homogeneous signal on T1WI and T2WI and marked enhancement on contrast-enhanced images.ConclusionsGiant cell tumors of the mobile spine with invasion into adjacent vertebrae are an unusual imaging finding. Radiologists should be familiar with this imaging characteristic.

Carbon reductant used in metallurgy industry is a considerable source of carbon dioxide emissions. Growing concerns over greenhouse effect have urgently prompted research in the application of hydrogen energy as an alternative. However, some basic kinetic problems in the hydrogen reduction process have not been clarified and resolved yet, such as the activation energy fluctuations caused by neglect of pore characteristics, along with the overly subjective division of the whole reaction process to analyze rate limiting mechanisms. In this study, a novel approach for acquiring instantaneous activation energy is proposed that is able to identify the activation energy at every reaction moment and thereby provide a quantitative basis for kinetics segmentation and rate-limiting mechanism determination. Moreover, due to the space requirements, the activation energy for the reaction stage controlled by nucleation and nuclei growth has a strong correlation with specific surface area. Whereas the restriction mechanisms of chemical reaction and diffusion are closely related to the average pore size. These results reveal that the different pore characteristics and changes in value have a direct influence on the corresponding rate limiting mechanisms and restriction degrees.

Mitochondrial dysfunction in heart triggers an integrated stress response (ISR) through phosphorylation of eIF2α and subsequent ATF4 activation. DAP3 Binding Cell Death Enhancer 1 (DELE1) is a mitochondrial protein recently found to be critical for mediating mitochondrial stress-triggered ISR (MSR)-induced eIF2α-ATF4 pathway activation. However, the specific role of DELE1 in heart at baseline or in response to mitochondrial stress remains largely unknown. In this study, we report that DELE1 is dispensable for cardiac development and function under baseline conditions. Conversely, DELE1 is essential for mediating an adaptive response to mitochondrial dysfunction-triggered stress in the heart, playing a protective role in mitochondrial cardiomyopathy.

General practitioners (GPs) are ideally placed to have a much larger role in detection and management of familial hypercholesterolaemia (FH) among their patients. The aim of this study was to seek the reflections of practice staff and newly diagnosed patients with FH on the implementation of an FH model of care in the general practice setting.Qualitative descriptive methodology was used. Interviews were conducted with 36 practice staff and 51 patients from 15 practices participating in the study.Data were analysed thematically and coded into themes - efficacy of GP training, screening for FH, model of care, patient awareness and cascade testing.Findings reflect the real-world clinical experience of Australian general practice and the acceptability of the model of care for both patients with FH and practice staff. Patient health literacy is a barrier to both management of FH and cascade testing. A systematic approach to cascade testing is required.

Studies exploring the association of tetrabromobisphenol A (TBBPA) with breast cancer and related mechanisms are limited. To investigate the relationship between TBBPA levels in breast adipose and breast cancer, we carried out case-control research. As well as further examine the mediating role of adipose metabolites between TBBPA and breast cancer using the metabolomics approach. In this study, the concentration of TBBPA was determined utilizing ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) after a solid phase extraction (SPE) pretreatment. High-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) was employed to analyze adipose metabolomics. Evaluation of metabolites linked to TBBPA exposure and breast cancer was performed utilizing mediation analysis. With an estimated OR (95%CI) of 1.153 (1.023, 1.299), TBBPA was firmly linked with breast cancer. We also used propensity score matching analysis and sensitivity analysis to reduce the effect of confounding factors on the results. Metabolomics of adipose suggested significant perturbation in the linoleic acid metabolism pathway. In addition, for PC (16:0/16:0) as phospholipids, a mediation effect on the associations of TBBPA exposure with breast cancer risks was observed (estimated mediation percentage: 56.58%). Understanding the relationship between TBBPA exposure and the risk of breast cancer may be facilitated by the findings, which point to potential mediation metabolites.

Familial hypercholesterolaemia (FH) can be effectively detected and managed in primary care, but the health economic evidence for this is scarce. The aim of this study was to examine management pathways and cost implications of FH screening and management in Australian general practice.Cost-effectiveness outcomes were projected using a life table model. Data was used from 133 patients in 15 Australian general practice clinics from an earlier screening and management study. Costing and mortality data were sourced from governmental sources and published literature.Most patients had a regular general practice consultation at baseline (82%), though the proportion seen under a chronic disease management item at follow-up increased to 23%. The median cost of management was $275 per annum in the first year of management. Managing patients with statins up to the age of 60 years yielded an increase of 248,954 life-years at a cost of $759 million, representing a cost per life-year gained of $3047.Screening and management of FH in general practice has the potential for substantial health benefits while requiring relatively modest investments from the health system.

The vision system of a fruit picking robot must perform two difficult tasks, the accurate pixel-wise instance segmentation of fruit and the correct detection of picking points. Due to the unsatisfactory performance of the vision system on these tasks, the picking performance of the robot is insufficient and its application is not prevalent. In this study, performing fruit instance segmentation and the localization of picking points, a vision algorithm using RGB images was designed in a deep learning framework for a potential visual system of mango picking robots. The algorithm not only performed these two tasks successfully, but also integrated them into an end-to-end network, in which parallel branches performed the two tasks simultaneously. The average precision (at IoU of 0.75) and the average recall of instance segmentation reached 0.947 and 0.929 respectively, and the best precision and recall of picking-point detection reached 0.984 and 0.908 respectively. In addition, the tasks face various illumination and background interference in outdoor orchards, along with complex problems in terms of occlusion, overlap and object scale. In this study, the performance of the vision system was analysed in detail on several datasets and subsets of the various complex conditions, and the major factors that affect the performance were discussed. The results demonstrated that this system was robust against various illuminations and complex backgrounds, and yielded satisfactory segmentation and picking-point detection performances for minor and medium occlusion or overlap, and for medium and large mangoes. The model visualization and the influence analysis of model training demonstrated the training process and modelling effect of the deep learning network.

Rationale and Objectives To evaluate the value of a radiomics nomogram for preoperative differentiating hepatocellular adenoma (HCA) from hepatocellular carcinoma (HCC) in the noncirrhotic liver. Materials and Methods One hundred and thirty-one patients with HCA (n = 46) and HCC (n = 85) were divided into a training set (n = 93) and a test set (n = 38). Clinical data and CT findings were analyzed. Radiomics features were extracted from the triphasic contrast CT images. A radiomics signature was constructed with the least absolute shrinkage and selection operator algorithm and a radiomics score was calculated. Combined with the radiomics score and independent clinical factors, a radiomics nomogram was developed by multivariate logistic regression analysis. The performance of the radiomics nomogram was assessed by calibration, discrimination and clinical usefulness. Results Gender, age, and enhancement pattern were the independent clinical factors. Three thousand seven hundred and sixty-eight features were extracted and reduced to 7 features as the optimal discriminators to build the radiomics signature. The radiomics nomogram (area under the curve [AUC], 0.96; 95% confidence interval [CI], 0.93–0.99) and the clinical factors model (AUC, 0.93; 95%CI, 0.88–0.99) showed better discrimination capability (p = 0.001 and 0.047) than the radiomics signature (AUC, 0.83; 95%CI, 0.74–0.92) in the training set. In the test set, the radiomics nomogram (AUC, 0.94; 95%CI, 0.87–1.00) performed better (p = 0.013) than the radiomics signature (AUC, 0.75; 95%CI, 0.59–0.91). Decision curve analysis showed the radiomics nomogram outperformed the clinical factors model and the radiomics signature in terms of clinical usefulness. Conclusion The CT-based radiomics nomogram has the potential to accurately differentiate HCA from HCC in the noncirrhotic liver.

Background Lipoprotein(a) (Lp[a]) is a causal risk factor for atherosclerotic cardiovascular disease (ASCVD). Proprotein convertase subtilisin/kexin‐9 monoclonal antibodies (PCSK9mAbs) can lower Lp(a) levels in clinical trials, but their effects in patients with elevated Lp(a) in clinical practice remain unclear. Aims To investigate the effectiveness and safety of PCSK9mAbs in lowering plasma Lp(a) in patients with elevated Lp(a) concentrations in a lipid clinic. Methods This was an open‐label study of 53 adult patients with elevated Lp(a) concentration (≥0.5 g/L). Clinical, biochemical, and safety data were collected before and on treatment with evolocumab or alirocumab over a mean period of 11 months. Results Treatment with a PCSK9mAb resulted in a significant reduction of 0.29 g/L (−22%) in plasma Lp(a) concentration (p.05 in all). 7.5% and 47% of the patients attained a target concentration of Lp(a)

Background: Guidelines on lipid disorders are constantly evolving. General practitioners regularly face critical decisions about the best treatment strategies for individual patients. Cardiovascular disease (CVD) is common, with most morbidity and mortality due to atherosclerosis. Raised low-density lipoprotein cholesterol (LDL-C) is the most atherogenic component - lowering it lowers the risk of future cardiovascular events. Objective: The aim of this article is to provide an evidence-informed summary of national guidelines and recent research to help clinicians reduce the risk of atherosclerotic CVD and improve health service delivery through improved lipid management strategies. Discussion: Elevated plasma lipids, especially LDL-C, increase the likelihood of a CVD event over time. Knowledge of family and personal histories plus other risk factors for CVD should alert clinicians to the need for treatment. The greater the overall burden of combined risk factors, the greater the lifetime risk. This update provides new information that informs future approaches for improving lipid management in Australian general practice.

Aims: mcr-1 and blaNDM-1 co-harboring isolates have been reported, usually reside on different plasmids, suggesting co-transfer possibility of the two genes from separate donors to the same recipie...

Lipoprotein(a) (Lp(a)) is a low-density lipoprotein-like particle containing apolipoprotein(a) (apo(a)) that increases the risk of atherosclerotic cardiovascular disease (ASCVD) in familial hypercholesterolemia (FH). Postprandial redistribution of apo(a) protein from Lp(a) to triglyceride-rich lipoproteins (TRLs) may also increase the atherogenicity of TRL particles. Omega-3 fatty acid (ω3FA) supplementation improves postprandial TRL metabolism in FH subjects. However, its effect on postprandial apo(a) metabolism has yet to be investigated.We carried out an 8-week open-label, randomized, crossover trial to test the effect of ω3FA supplementation (4 g/day) on postprandial apo(a) responses in FH patients following ingestion of an oral fat load. Postprandial plasma total and TRL-apo(a) concentrations were measured by liquid chromatography with tandem mass spectrometry, and the corresponding areas under the curve (AUCs) (0-10h) were determined using the trapezium rule.Compared with no ω3FA treatment, ω3FA supplementation significantly lowered the concentrations of postprandial TRL-apo(a) at 0.5 (-17.9%), 1 (-18.7%), 2 (-32.6%), and 3 h (-19.2%) (P＜0.05 for all). Postprandial TRL-apo(a) AUC was significantly reduced with ω3FA by 14.8% (P＜0.05). By contrast, ω3FA had no significant effect on the total AUCs of apo(a), apoC-III, and apoE (P＞0.05 for all). The decrease in postprandial TRL-apo(a) AUC was significantly associated with changes in the AUC of triglycerides (r=0.600; P ＜0.01) and apoB-48 (r=0.616; P＜0.01).Supplementation with ω3FA reduces postprandial TRL-apo(a) response to a fat meal in FH patients; this novel metabolic effect of ω3FA may have implications on decreasing the risk of ASCVD in patients with FH, especially in those with elevated plasma triglyceride and Lp(a) concentrations. However, the clinical implications of these metabolic findings require further evaluation in outcome or surrogate endpoint trials.

Hepatic steatosis has been associated with increased risk of coronary artery disease. Individuals with familial hypercholesterolaemia have accelerated but variable progression of coronary artery disease. We investigated whether hepatic steatosis is associated with novel coronary atherosclerosis biomarkers in adults with heterozygous familial hypercholesterolaemia, using comprehensive coronary computed tomographic angiography.We conducted a cross-sectional study of 213 asymptomatic patients with familial hypercholesterolaemia (median age 54.0 years, 59 % female) who underwent coronary computed tomographic angiography for cardiovascular risk assessment in an outpatient clinic. High-risk plaque features, plaque volume and pericoronary adipose tissue attenuation were assessed. From concurrently captured upper abdominal images, severity of hepatic steatosis was computed, as liver minus spleen computed tomography attenuation and stratified into quartiles.Of 213 familial hypercholesterolaemia patients, 59 % had coronary artery calcium, 36 % obstructive coronary artery disease (≥50 % stenosis) and 77 % high-risk plaque features. Increasing hepatic steatosis was associated with higher calcium scores, more high-risk plaque features and presence of obstructive coronary artery disease. Hepatic steatosis was associated with the presence of high-risk plaque features (OR: 1.48; 95 % CI: 1.09-2.00; p = 0.01), particularly in the proximal coronary segments (OR: 1.52; 95 % CI: 1.18-1.96; p = 0.001). Associations persisted on multivariable logistic regression analysis adjusting for cardiometabolic factors, obstructive coronary artery disease and calcium score. Hepatic steatosis was associated with higher plaque volumes (Q4: 499 mmHepatic steatosis is associated with multiple indices of advanced coronary atherosclerosis in familial hypercholesterolaemia patients, particularly high-risk plaque features, independent of conventional cardiovascular risk factors and markers. This may involve specific mechanisms related to hepatic steatosis.N/A.

At present, the solution and qualitative analysis of nonlinear partial differential equations occupy a very important position in the study of dynamics. In this paper, the bilinear Backlund transformation of the (2+1)-dimensional variable-coefficient G a r d n e r − K P ( G K P ) equation is deduced by virtue of Hirota bilinear form, which consists of seven bilinear equations and involves ten arbitrary parameters. On the basis of the bilinear Backlund transformation, the traveling wave solution of the equation is obtained. Then the test function of the interaction solution of the positive quadratic function and exponential function of the (2+1)-dimensional variable-coefficient G K P equation is constructed, and then the test function of the positive quadratic function, hyperbolic cosine function and the interaction solution of the cosine function is constructed. With the help of mathematical symbol software Maple and Mathematica, the solitary wave solutions of (2+1)-dimensional variable-coefficient G K P equation is obtained by using Maple and Mathematica, and the interaction phenomena between a Lump wave and a Kink wave, a Lump wave and Multi-Kink waves are discussed.

Familial hypercholesterolaemia (FH) is a highly penetrant monogenic disorder present from birth that markedly elevates plasma low-density lipoprotein (LDL)-cholesterol (LDL-C) concentration and, if untreated, leads to premature atherosclerosis and coronary artery disease (CAD). At a prevalence of 1:250 individuals, with over 90% undiagnosed, recent estimates suggest that there are approximately 22 000 children and adolescents with FH in Australia and New Zealand. However, the overwhelming majority remain undetected and inadequately treated until adulthood or after their first cardiac event. The guidance in this paper aims to increase awareness about paediatric FH and provide practical advice for the diagnosis and management of FH in children and adolescents. Recommendations are given on the detection, diagnosis, assessment and management of FH in children and adolescents. Recommendations are also made on genetic testing, including counselling and the potential for universal screening programmes. Practical guidance on management includes treatment of non-cholesterol risk factors, and safe and appropriate use of LDL-C lowering therapies, including statins, ezetimibe, PCSK9 inhibitors and lipoprotein apheresis. Models of care for FH need to be adapted to local and regional health care needs and available resources. Targeting the detection of FH as a priority in children and young adults has the potential to alter the natural history of atherosclerotic cardiovascular disease and recognise the promise of early detection for improving long-term health outcomes. A comprehensive implementation strategy, informed by further research, including assessments of cost-benefit, will be required to ensure that this new guidance benefits all families with or at risk of FH.

With research progress on longevity, we have gradually recognized that cardiac aging causes changes in heart structure and function, including progressive myocardial remodeling, left ventricular hypertrophy, and decreases in systolic and diastolic function. Elucidating the regulatory mechanisms of cardiac aging is a great challenge for biologists and physicians worldwide. In this review, we discuss several key molecular mechanisms of cardiac aging and possible prevention and treatment methods developed in recent years. Insights into the process and mechanism of cardiac aging are necessary to protect against age-related diseases, extend lifespan, and reduce the increasing burden of cardiovascular disease in elderly individuals. We believe that research on cardiac aging is entering a new era of unique significance for the progress of clinical medicine and social welfare.

Background MicroRNAs play an important role in many fundamental biological and pathological processes. Defining the microRNAs profile underlying the processes by beneficial and detrimental lifestyles, including caloric restriction (CR), exercise and high-fat diet (HF), is necessary for understanding both normal physiology and the pathogenesis of metabolic disease. We used the microarray to detect microRNAs expression in livers from CR, EX and HF mice models. After predicted potential target genes of differentially expressed microRNAs with four algorithms, we applied GO and KEGG to analyze the function of predicted microRNA targets. Results We describe the overall microRNAs expression pattern, and identified 84 differentially expressed microRNAs changed by one or two or even all the three lifestyle modifications. The common and different enriched categories of gene function and main biochemical and signal transduction pathways were presented. Conclusions We provided for the first time a comprehensive and thorough comparison of microRNAs expression profiles in liver among these lifestyle modifications. With this knowledge, our findings provide us with an overall vision of microRNAs in the molecular impact of lifestyle on health as well as useful clues for future and thorough research of the role of microRNAs.

Non-proteinogenic trans-4-hydroxy- l -proline (t4HYP), a crucial naturally occurred amino acid, is present in most organisms. t4HYP is a regio- and stereo-selectively hydroxylated product of l -proline and a valuable building block for pharmaceutically important intermediates/ingredients synthesis. Microbial production of t4HYP has aroused extensive investigations because of its low-cost and environmentally benign features. Herein, we reported metabolic engineering of endogenous l -proline biosynthetic pathway to enhance t4HYP production in trace l -proline-producing Escherichia coli BL21(DE3) (21-S0). The genes responsible for by-product formation from l -proline, pyruvate, acetyl-CoA, and isocitrate in the biosynthetic network of 21-S0 were knocked out to channel the metabolic flux towards l -proline biosynthesis. PdhR was knocked out to remove its negative regulation and aceK was deleted to ensure isocitrate dehydrogenase’s activity and to increase NADPH/NADP+ level. The other genes for l -proline biosynthesis were enhanced by integration of strong promoters and 5′-untranslated regions. The resulting engineered E. coli strains 21-S1 ∼ 21-S9 harboring a codon-optimized proline 4-hydroxylase-encoding gene (P4H) were grown and fermented. A titer of 4.82 g/L of t4HYP production in 21-S6 overexpressing P4H was obtained at conical flask level, comparing with the starting 21-S0 (26 mg/L). The present work paves an efficient metabolic engineering way for higher t4HYP production in E. coli.

Drawing on organizational learning theory and literature on guanxi, this study examines how and why ambidextrous learning balance influences firm innovation capability in Chinese business circles. We propose a U-shaped relation between ambidextrous learning balance and firm innovation capability which is mediated by guanxi inertia and knowledge inertia in different ways. Specifically, ambidextrous learning balance has an inverted U-shaped impact on guanxi inertia and further influences firm innovation capability. Whereas, ambidextrous learning balance has a linear positive influence on innovation capability through a decreased level of knowledge inertia. Based on survey data collected from, The results obtained from a sample of 197 Chinese channel enterprises using SEMs analysis provide strong support for our hypotheses. In addition, the findings based on firms with unbalanced ambidextrous learning indicate that as opposed to exploratory learning, higher level of exploitative learning leads to an increase in guanxi inertia and a decrease in knowledge inertia. These conclusions reveal how ambidextrous learning balance influence innovation capability for a firm with inherent learning preference which is not discussed by the extant research. At the same time, this study fills the gap of ambidextrous learning balance by considering the influence of culture. Our work also informs foreign practitioners of the optimal ways of learning for innovation in China.

The second elliptic equation method is a more general form of Jacobi elliptic function expansion method, which can obtain more kinds of solutions of a nonlinear evolution equation. In this paper, the method is used to solve the Kdv-Burgers-Kuramoto (Benny) equation with variable coefficients, and its extremely rich solution properties are elucidated, among which the biperiodic solutions, solitary wave solutions and trigonometric periodic solutions are analyzed graphically.

Highlights A method of monitoring the working conditions of a slideway seedling-picking mechanism based on variational mode decomposition (VMD), envelope entropy, and energy entropy is proposed. Based on the criterion of envelope entropy minimization, the combination of the decomposition layer number and penalty factor in VMD is optimized to yield a satisfactory decomposition effect of the analyzed vibration signal. The BP-AdaBoost algorithm is used to improve the working condition classification performance for the slideway seedling-picking mechanism. The working-condition identification effect with the proposed method are compared with those through EMD-based, LMD-based, and EEMD-based methods. Abstract . The slideway seedling-picking mechanism is a type of rotating machinery. This study proposes a novel method of identifying the working conditions of slideway seedling-picking mechanisms for early fault diagnosis by utilizing a back-propagation adaptive boosting (BP-AdaBoost) algorithm based on variational mode decomposition (VMD) optimized by the envelope entropy. The experimental results demonstrate that the proposed method can effectively verify the four working conditions (normal state, slideway failure, cam failure, and spring failure). The overall recognition accuracy reaches 90.0% under the optimal combination of the decomposition layer number K and penalty factor a in VMD determined through the envelope entropy minimization criterion. Classification comparisons with empirical mode decomposition (EMD), local mean decomposition (LMD) and ensemble empirical mode decomposition (EEMD) integrated into the BP-AdaBoost algorithm indicate that the overall recognition accuracy of the proposed method is 18.1%, 16.9%, and 15.6% higher than the accuracies of the three conventional methods, respectively. Compared with the K-means, support vector machine (SVM) algorithms, BP-AdaBoost algorithm demonstrates a more dependable capability for identifying the working conditions. This study provides a useful reference for monitoring the working conditions of slideway seedling-picking mechanisms. Keywords: BP-AdaBoost algorithm, Energy entropy, Envelope entropy, Slideway seedling-picking mechanism, Variational mode decomposition, Working conditions.

Helicobacter pylori is a Gram-negative bacterium related to the development of peptic ulcers and stomach cancer. An increasing number of infected individuals are found to harbor antibiotic-resistant H. pylori, which results in treatment failure. Daphnetin, a traditional Chinese medicine, has a broad spectrum of antibacterial activity without the development of bacterial resistance. However, the antibacterial mechanisms of daphnetin have not been elucidated entirely. To better understand the mechanisms of daphnetin's effect on H. pylori, a label-free quantitative proteomics approach based on an EASY-nLC 1200 system coupled with an Orbitrap Fusion Lumos mass spectrometer was established to investigate the key protein differences between daphnetin- and non-daphnetin-treated H. pylori. Using the criteria of greater than 1.5-fold changes and adjusted p value

Based on Hirota bilinear formulation, the lump solutions to dimensionally reduced generalized variable coefficient B-type Kadomtsev-Petviashvili equation are obtained. The solution process is figured out and the solution properties are illustrated graphically. The present method can be extended to other non-linear equations.

IntroductionHeterozygous familial hypercholesterolaemia (heFH) is the most common monogenic cause of premature atherosclerotic cardiovascular disease. The precise diagnosis of heFH is established by genetic testing. This systematic review will investigate the risk factors that predict cardiovascular events in patients with a genetic diagnosis of heFH.Methods and analysisOur literature search will cover publications from database inception until June 2023. We will undertake a search of CINAHL (trial), clinicalKey, Cochrane Library, DynaMed, Embase, Espacenet, Experiments (trial), Fisterra, ÍnDICEs CSIC, LILACS, LISTA, Medline, Micromedex, NEJM Resident 360, OpenDissertations, PEDro, Trip Database, PubPsych, Scopus, TESEO, UpToDate, Web of Science and the grey literature for eligible studies. We will screen the title, abstract and full-text papers for potential inclusion and assess the risk of bias. We will employ the Cochrane tool for randomised controlled trials and non-randomised clinical studies and the Newcastle–Ottawa Scale for assessing the risk of bias in observational studies. We will include full-text peer-reviewed publications, reports of a cohort/registry, case–control and cross-sectional studies, case report/series and surveys related to adults (≥18 years of age) with a genetic diagnostic heFH. The language of the searched studies will be restricted to English or Spanish. The Grading of Recommendations, Assessment, Development and Evaluation approach will be used to assess the quality of the evidence. Based on the data available, the authors will determine whether the data can be pooled in meta-analyses.Ethics and disseminationAll data will be extracted from published literature. Hence, ethical approval and patient informed consent are not required. The findings of the systematic review will be submitted for publication in a peer-reviewed journal and presentation at international conferences.PROSPERO registration numberCRD42022304273.

Pesticide residues have become a healthy threaten of human beings. Among the pesticides, many of them have neurotoxicity. Extracellular Regulated Protein Kinases (ERK) pathway is an important signaling pathway that regulates a variety of downstream progress. In this work, peach (PRUNUS persica) and cherry (PRUNUS cerasus) were sampled from over 300 plantations in China and assessed for the residue risk. In mechanism studies, high-risk pesticide Avermectin showed a high activity inhibiting three neurotoxicity models, SH-SY5Y, PC-12 and SK-N-SH cells. At protein levels, ERK pathway proteins and their downstream proteins were obviously down-regulated. Moreover, the effects of low-dose Avermectin can be accumulated at protein levels in the low-dose long-term chronic toxicology detection.

Nepetalactol, an iridoid with four chiral carbons, is a crucial component of aphid sex pheromones that have been employed with great success to control the insect-related diseases. Despite of agricultural usage as end products, iridoids are fundamental biosynthetic intermediates for pharmaceutically important monoterpenoid indole alkaloids such as camptothecin (CAM) and vinca alkaloids. Herein we characterized 10-hydroxygeraniol oxidoreductase (10HGO) and iridoid synthase (IS) from Camptotheca acuminata, a CAM-producing plant, and reported their application in biological preparation of nepetalactol. Ca10HGO and CaIS were respectively cloned from C. acuminata, overexpressed in Escherichia coli, and purified to homogeneity. Ca10HGO catalyzes the oxidation of 10-hydroxygeraniol into 10-oxogeranial, in which NADP+ was reduced to NADPH. CaIS catalyzes nepetalactol formation from 10-oxogeranial using NADPH cofactor. The net outcome of the two reactions generate nepetalactol from 10-hydroxygeraniol efficiently, indicating NADP+ - NADPH recycling. Ca10HGO and CaIS were co-overexpressed in E. coli under optimized fermentation conditions to prepare cell-based catalysts that catalyze the conversion of 10-hydroxygeraniol into nepetalactol. The present work shows the enzymatic conversion of 10-hydroxygeraniol into nepetalactol involved in CAM biosynthesis. Co-overexpression of Ca10HGO and CaIS in E. coli is an alternative valuable cell-based biotransformation process with regenerating recycling of NADP+ - NADPH cofactors for nepetalactol preparation.