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Abstract As we know, the horizon area of a black hole will increase when it absorbs matter. Based on Barrow’s concept of a fractal black hole horizon, it has been proposed (Phys Lett B 831:137181, 2022) that for a spherically fractal structure, the minimum increase in the horizon area is the area of the smallest bubble sphere. The corresponding black hole entropy is of a logarithmic form, which is similar to that of Boltzmann entropy under a certain condition. Based on this, we re-derive the entropy of Barrow’s Einstein–power-Yang–Mills (EPYM) anti-de Sitter (AdS) black hole, and calculate its temperature and heat capacity. There exists an interesting phenomenon wherein the ratio between Barrow’s temperature and the Hawking temperature of the EPYM AdS black hole is fully consistent with that of other Schwarzschild-like black holes. The Barrow and Hawking temperatures within a certain range of $$\Lambda $$ Λ are found to increase monotonically, and the corresponding heat capacities are all positive, which means that these black holes are thermodynamically stable. In addition, for Barrow’s EPYM AdS black hole, its heat capacity has a Schottky anomaly-like behavior, which may reflect the existence of a discrete energy level and microscopic degrees of freedom.

The ultracold atomic Fermi gas provides a flexible and controllable experimental platform for exploring magnetic impurity states. In this study, we theoretically examine the magnetic impurity states in a Fermi system with spin-1/2 and spin-3/2 under a local magnetic field. Firstly, the spin-1/2 impurity system contains three types of magnetic solutions. One type magnetic solution with higher energy can be regarded as the result of induced magnetization of a trivial solution, while the other two types magnetic solutions with lower energy can be understood as the results of Zeeman splitting of nontrivial solutions with double degeneracy. Notably, the magnetic solution corresponding to the spin state parallel to the Zeeman magnetic field is always the most stable in terms of the energy. Secondly, we extend the idea of studying spin-1/2 impurity to spin-3/2 impurity, where the half-filled state of impurity atoms is calculated. We found that four types of magnetic solutions at zero magnetic field were split into four, six, four, and twelve new magnetic solutions in the presence of a Zeeman magnetic field, respectively. We obtained that the magnetic solution corresponding to the spin state parallel to the magnetic field is the most stable, and its energy is lower than that of the corresponding magnetic solution at zero magnetic field. Therefore, the introduction of a local magnetic field is beneficial for the formation of magnetic impurity states. Finally, the calculated data illustrate that the Anderson impurity model we adopt exhibits invariance under the combined transformations of spin-flip and particle–hole.

Abstract Considering the nonlinearity of the Yang Mills charge, we investigate the Joule–Thomson expansion for the Einstein–Power–Yang–Mills AdS black holes in the context of the gauge-gravity duality. Under this framework, we calculate the Joule–Thomson coefficient, describe all relevant inversion and isenthalpic curves in the temperature-pressure plane that determining in this manner the corresponding cooling and heating regions. Finally we analyze the effect of the charge nonlinearity on the Joule–Thomson expansion.

Background: Cytokines modulate the glioma tumor microenvironment, influencing occurrence, progression, and treatment response. Strategic cytokine application may improve glioma immunotherapy outcomes. Gliomas remain refractory to standard therapeutic modalities, but immunotherapy shows promise given the integral immunomodulatory roles of cytokines. However, systematic evaluation of cytokine glioma immunotherapy research is absent. Bibliometric mapping of the research landscape, recognition of impactful contributions, and elucidation of evolutive trajectories and hot topics has yet to occur, potentially guiding future efforts. Here, we analyzed the structure, evolution, trends, and hotspots of the cytokine glioma immunotherapy research field, subsequently focusing on avenues for future investigation.Methods: This investigation conducted comprehensive bibliometric analyses on a corpus of 1529 English-language publications, from 1 January 2000, to 4 October 2023, extracted from the Web of Science database. The study employed tools including Microsoft Excel, Origin, VOSviewer, CiteSpace, and the Bibliometrix R package, to systematically assess trends in publication, contributions from various countries, institutions, authors, and journals, as well as to examine literature co-citation and keyword distributions within the domain of cytokines for glioma immunotherapy. The application of these methodologies facilitated a detailed exploration of the hotspots, the underlying knowledge structure, and the developments in the field of cytokines for glioma immunotherapy.Results: This bibliometric analysis revealed an exponential growth in annual publications, with the United States, China, and Germany as top contributors. Reviews constituted 17% and research articles 83% of total publications. Analysis of keywords like “interleukin-13,” “TGF-beta,” and “dendritic cells” indicated progression from foundational cytokine therapies to sophisticated understanding of the tumor microenvironment and immune dynamics. Key research avenues encompassed the tumor microenvironment, epidermal growth factor receptor, clinical trials, and interleukin pathways. This comprehensive quantitative mapping of the glioma immunotherapy cytokine literature provides valuable insights to advance future research and therapeutic development.Conclusion: This study has identified remaining knowledge gaps regarding the role of cytokines in glioma immunotherapy. Future research will likely focus on the tumor microenvironment, cancer vaccines, epidermal growth factor receptor, and interleukin-13 receptor alpha 2. Glioma immunotherapy development will continue through investigations into resistance mechanisms, microglia and macrophage biology, and interactions within the complex tumor microenvironment.

The conservation of the ecosystem in the Yellow River source region (YRSR) has become a crucial national strategy in China, emphasizing the need for evaluating ecosystem integrity to identify priority conservation areas (PCAs). Current research has primarily employed a limited number of indicators or a single dimension to assess ecosystem integrity, which may overlook comprehensive considerations required for effective conservation planning. To address this, a multidimensional approach was adopted in this study to evaluate ecosystem integrity, incorporating three dimensions: biological diversity, ecosystem function, and stress components. The MaxEnt and Fragstats models were employed to create an ecosystem integrity map and Marxan was used to identify priority conservation areas within the YRSR. Our results showed that (1) the index of ecosystem integrity gradually declined from east to west, consistent with the spatial distribution of biodiversity and ecosystem function, whereas the stress component exhibits a decreasing trend from northeast to southwest. (2) the priority protected areas were distributed in Maduo, Ruoergai, Maqu, Maqin, Henan, Gande, and Jiuzhi Counties. Furthermore, to address existing protection gaps and enhance connectivity, it was recommended to incorporate an additional 27,644 km2 of southwest and central YRSR into the PCAs. Overall, the study offered practical recommendations for the conservation of the ecosystem in the YRSR. In addition, the method of PCAs determination in this study could provide a reference for the government’s growing nature conservation affairs, which will contribute to sustainable development.

BackgroundElderly individuals diagnosed with high-grade gliomas frequently experience unfavorable outcomes. We aimed to design two web-based instruments for prognosis to predict overall survival (OS) and cancer-specific survival (CSS), assisting clinical decision-making.MethodsWe scrutinized data from the SEER database on 5,245 elderly patients diagnosed with high-grade glioma between 2000-2020, segmenting them into training (3,672) and validation (1,573) subsets. An additional external validation cohort was obtained from our institution. Prognostic determinants were pinpointed using Cox regression analyses, which facilitated the construction of the nomogram. The nomogram’s predictive precision for OS and CSS was gauged using calibration and ROC curves, the C-index, and decision curve analysis (DCA). Based on risk scores, patients were stratified into high or low-risk categories, and survival disparities were explored.ResultsUsing multivariate Cox regression, we identified several prognostic factors for overall survival (OS) and cancer-specific survival (CSS) in elderly patients with high-grade gliomas, including age, tumor location, size, surgical technique, and therapies. Two digital nomograms were formulated anchored on these determinants. For OS, the C-index values in the training, internal, and external validation cohorts were 0.734, 0.729, and 0.701, respectively. We also derived AUC values for 3-, 6-, and 12-month periods. For CSS, the C-index values for the training and validation groups were 0.733 and 0.727, with analogous AUC metrics. The efficacy and clinical relevance of the nomograms were corroborated via ROC curves, calibration plots, and DCA for both cohorts.ConclusionOur investigation pinpointed pivotal risk factors in elderly glioma patients, leading to the development of an instrumental prognostic nomogram for OS and CSS. This instrument offers invaluable insights to optimize treatment strategies.

The exact mechanisms of the development of autism, a multifactorial neurological disorder, are not clear. The pathophysiology of autism is complex, and investigations at the cellular and molecular levels are ongoing to provide clarity. Mutations in specific genes have been identified as risk factors for autism. The role of heavy metals in the pathogenesis of autism is subject to many studies and remains debatable. Although no exact neuronal phenotypes have been identified linked to autistic symptoms, overproduction and reduction of specific neurons have been implicated. A growing literature on generating genetic and non-genetic models of autism aims to help with understanding mechanistic studies that can explain the complexity of the disorder. Both genetic and non-genetic methods of zebrafish have been used to model autism. For several human autism risk genes, validated zebrafish mutant models have been generated. There is growing evidence indicating a potential link between autism and inorganic arsenic exposure. We have previously shown that inorganic arsenic induces supernumerary spinal motor neurons via Sonic hedgehog (Shh) signaling pathway, and Cdk5 knockdown causes an overproduction of cranial and spinal motor neurons in zebrafish. Here, in this review, we provide a perspective on what these findings of neurogenic phenotypes mean in terms of dysregulated pathways of motor neuron development and their applicability to understanding cellular and molecular underpinnings of autism.

Abstract In order to improve the construction technology level of the connection nodes of prefabricated buildings and improve the mechanical properties, fluidity and economy of the connection mortar, this paper adopts the orthogonal experimental design to improve the cement mortar by adding polymer dispersible polymer powder. A modified high-performance mortar with 1d compressive strength of 11Mpa, 3d compressive strength of 19Mpa, 7d compressive strength of 26Mpa, fluidity of 102 mm and final compressive strength higher than M25 was studied. The factors and levels of the orthogonal test are: mortar ratio 1:3,1:4,1:5; silica powder content of 4%,6%,8%; dispersible polymer powder content of 3%,5%,7%. After research, the optimal mixing ratio of modified high-performance mortar is 1:3, the content of silicon powder is 6%, the content of redispersible latex powder is 3%, the content of early strength water reducing agent is 0.1%, and the content of defoamer is 0.5%. The new modified high-performance cement mortar is characterized by short setting time and high early strength, which provides a new idea for the connecting materials of prefabricated buildings, which is of great significance for improving the integrity of prefabricated buildings and the durability of the connection.

Steel frame infilled with composite plate shear wall (SF-CPSW) is an efficient lateral load resisting structure with significant ductility and energy dissipation capacity. In this paper, CPSW comprises the infill steel plate, encased concrete panel and headed studs. The steel frames (SFs) are expected to sustain the vertical load, while as the boundary members of the CPSW, they also influence the lateral behaviors of structure. However, the research on the interactions or plasticity development of SF-CPSW is limited. Thus, its energy dissipation mechanism is unclear to date. This paper conducts finite element analyses on the hysteresis performance and energy dissipation mechanism of SF-CPSW structure under cyclic loading. The hysteresis and skeleton of lateral load-drift ratio responses, distributions and developments of internal forces, stresses and strains and the energy assignments are studied to reveal the mechanisms of lateral load-resisting and plasticity development of SF-CPSW. The effects of steel plate thickness, beam cross-section, column cross-section and concrete panel thickness on the hysteresis performance and energy assignment are investigated to propose the energy dissipation mechanism and associated design methods. The results indicate that the energy dissipation of SF-CPSW is governed by the plastic shearing of infill steel plate and beam web due to the shear force transfers and bending restraints from CPSW to the steel frame. Besides, the columns resist portions of lateral load under such interactions. The structural energy dissipation should develop successively by the shear yielding of steel plate, the shear yielding of beam and column, the flexural yielding of beam, the plastic buckling of steel plate and the flexural yielding of column. As the major members for energy dissipation, the yield shear strength of beam should be higher than 27.5% yield shear strength of infill steel plate.

Background: The role of cystathionine γ-lyase (CTH) in the prognosis and immune invasion of hepatocellular carcinoma (HCC) remains poorly understood. Methods: In this study, the clinical data of patients with HCC were analyzed, and the expression level of CTH was compared between HCC and normal tissues using the R package and various databases. Results: We found that CTH expression was significantly decreased in HCC compared with normal tissues, and its expression was associated with various clinicopathological factors, including tumor stage, gender, tumor status, residual tumor, histologic stage, race, alpha-fetoprotein (AFP), albumin, drinking, and smoking. Our results suggest that CTH might be a protective factor for the survival of patients with HCC. Further functional analysis revealed that high CTH expression was enriched in the Reactome signaling by interleukins and the Reactome neutrophil degranulation. Moreover, CTH expression was closely correlated with a variety of immune cells, including a negative correlation with the CD56 (bright) NK cells and follicular helper T cell (TFH), while a positive correlation with Th17 cells and central memory T cell (Tcm). High expression of CTH in immune cells predicted a better prognosis of HCC. Our findings further indicated Pyridoxal phosphate, l-cysteine, Carboxymethylthio-3-(3-chlorophenyl)-1,2,4-oxadiazol, 2-[(3-Hydroxy-2-Methyl-5-Phosphonooxymethyl-Pyridin-4-Ylmethyl)-Imino]-5-phosphono-pent-3-enoic acid and L-2-amino-3-butynoic acid as potential target candidate medications for HCC treatment based on CTH. Conclusion: Our study suggests that CTH can serve as a biomarker to predict the prognosis and immune infiltration of HCC.

Alpine grasslands are important ecosystems on the Qinghai–Tibet Plateau and are extremely sensitive to climate change. However, the spatial responses of plant species diversity and biomass in alpine grasslands to environmental factors under the background of global climate change have not been thoroughly characterized. In this study, a random forest model was constructed using grassland ground monitoring data with satellite remote sensing data and environmental variables to characterize the plant species diversity and aboveground biomass of grasslands in the Three-River Headwaters Region within the Qinghai–Tibet Plateau and analyze spatial variation in the relationship between the plant species diversity and aboveground biomass and their driving factors. The results show that (1) the selection of characteristic variables can effectively improve the accuracy of random forest models. The stepwise regression variable selection method was the most effective approach, with an R2 of 0.60 for the plant species diversity prediction model and 0.55 for the aboveground biomass prediction model, (2) The spatial distribution patterns of the plant species diversity and aboveground biomass in the study area were similar, they were both high in the southeast and low in the northwest and gradually decreased from east to west. The relationship between the plant species diversity and aboveground biomass varied spatially, they were mostly positively correlated (67.63%), but they were negatively correlated in areas with low and high values of plant species diversity and aboveground biomass, and (3) Analysis with geodetector revealed that longitude, average annual precipitation, and elevation were the main factors driving variation in the plant species diversity and aboveground biomass relationship. We characterized plant species diversity and aboveground biomass, as well as their spatial relationships, over a large spatial scale. Our data will aid biodiversity monitoring and grassland conservation management, as well as future studies aimed at clarifying the relationship between biodiversity and ecosystem functions.

Parthenolide (PTL or PAR) was first isolated from Magnolia grandiflora and identified as a small molecule cancer inhibitor. PTL has the chemical structure of C15H20O3 with characteristics of sesquiterpene lactones and exhibits the biological property of inhibiting DNA biosynthesis of cancer cells. In this review, we summarise the recent research progress of medicinal PTL, including the therapeutic effects on skeletal diseases, cancers, and inflammation-induced cytokine storm. Mechanistic investigations reveal that PTL predominantly inhibits NF-κB activation and other signalling pathways, such as reactive oxygen species. As an inhibitor of NF-κB, PTL appears to inhibit several cytokines, including RANKL, TNF-α, IL-1β, together with LPS induced activation of NF-κB and NF-κB -mediated specific gene expression such as IL-1β, TNF-α, COX-2, iNOS, IL-8, MCP-1, RANTES, ICAM-1, VCAM-1. It is also proposed that PTL could inhibit cytokine storms or hypercytokinemia triggered by COVID-19 via blocking the activation of NF-κB signalling. Understanding the pharmacologic properties of PTL will assist us in developing its therapeutic application for medical conditions, including arthritis, osteolysis, periodontal disease, cancers, and COVID-19-related disease.

IntroductionThe most important chemotherapy treatment for glioma patients is temozolomide. However, the development of drug resistance severely restricts the use of temozolomide. Therefore, elucidating the mechanism of temozolomide resistance, enhancing temozolomide sensitivity, and extending patient survival are urgent tasks for researchers.MethodsTemozolomide resistance hub differential genes were identified using differential analysis and protein interaction analysis from the GEO datasets (GSE100736 and GSE113510). These genes were further studied in glioma patients treated with temozolomide in the TCGA and CGGA databases. Patients from the mRNAseq_325 dataset (CGGA) were considered as the training set to construct a risk model for predicting glioma sensitivity to temozolomide, while patients from the mRNAseq_693 dataset (CGGA) and TCGA-GBM dataset were considered as the validation set to evaluate the performance of models. PCR and western blot were performed to determine the difference in expression of the feature gene DACH1 between glioma cells and temozolomide-resistant glioma cells. The alterations in the sensitivity of tumor cells to temozolomide were also observed after DACH1 was silenced. The patients were then divided into two groups based on the expression of DACH1, and the differences in patient survival rates, molecular pathway activation, and level of immune infiltration were compared.ResultsBased on four signature genes (AHR, DACH1, MGMT, and YAP1), a risk model for predicting glioma sensitivity to temozolomide was constructed, and the results of timeROC in both the training and validation sets showed that the model had good predictive performance. The expression of the signature gene DACH1 was significantly downregulated in temozolomide-resistant cells, according to the results of the PCR and western blot experiments. The sensitivity of tumor cells to temozolomide was significantly reduced after DACH1 was silenced. DACH1 probably regulates temozolomide resistance in glioblastoma through the transcriptional dysregulation in cancer and ECM.DiscussionThis study constructs a risk model that can predict glioma susceptibility to temozolomide and validates the function of the feature gene DACH1, which provides a promising target for the research of temozolomide resistance.

Abstract Background The natural history and genotype–phenotype correlation of Pelizaeus–Merzbacher disease (PMD) of Chinese patients has been rarely reported. Method Patients who met the criteria for PMD were enrolled in our study. Genomic analysis was conducted by multiplex ligation probe amplification (MLPA) and Sanger or whole-exome sequencing (WES). Natural history differences and genotype–phenotype correlations were analyzed. Result A total of 111 patients were enrolled in our follow-up study. The median follow-up interval was 53 m (1185). Among PMD patients, developmental delay was the most common sign, and nystagmus and hypotonia were the most common initial symptoms observed. A total of 78.4% of the patients were able to control their head, and 72.1% could speak words. However, few of the patients could stand (9.0%) or walk (4.5%) by themselves. Nystagmus improved in more than half of the patients, and hypotonia sometimes deteriorated to movement disorders. More PLP1 point mutations patients were categorized into severe group, while more patients with PLP1 duplications were categorized into mild group (p

Abstract A compact damping ring with a limited circumference of about 160 m is proposed for producing kilowatt-level coherent EUV radiation. The electron bunch in the storage ring is modulated by a 257 nm wavelength seed laser with the help of the angular-dispersion-induced micro-bunching method (Feng and Zhao in Sci Rep 7:4724, 2017), coherent radiation at 13.5 nm with an average power of about 2.5 kW can be achieved with the state-of-the-art accelerator and laser technologies.

BackgroundC-arm-guided percutaneous puncture balloon compression alone has risk factors of puncture failure, complications, and poor prognosis. Robot-assisted PBC can effectively increase the one-time puncture success rate and improve the safety of the procedure. However, evidence on the superiority of robot-assisted PBC over C-arm-guided PBC alone remains relatively limited.MethodsRetrospective analysis The clinical data of 60 patients with trigeminal neuralgia aged 60 years or older in the Department of Neurosurgery of the Fourth Hospital of Harbin Medical University from January 2021 to October 2021. There were 29 males and 31 females, and the patients’ ages ranged from 60 to 79 years, with an average of 71.63 ± 5.12 years. Two groups were divided according to the surgical method, the C-arm guidance-only group (30 cases, n = 30) and the robot-assisted group (30 cases, n = 30). The success rate of first puncture, total operation time, number of “pear-shaped” balloons, number of C-arm x-ray scans, and immediate postoperative relief rate were recorded in both groups, and follow-up was performed to evaluate the postoperative results and complications. The overall evaluation of postoperative results and complications was performed.ResultsIntraoperative balloon compression was successfully completed in all 60 patients, and the first puncture success rate was higher in the robot-assisted group than in the simple C-arm group, with a significant difference between the two groups (P 0.05). By the final follow-up, the mean VAS score of the robot-assisted group was lower than that of the simple C-arm group, and both were statistically significant (P

UAV multitarget detection plays a pivotal role in civil and military fields. Although deep learning methods provide a more effective solution to this task, changes in target size, shape change, occlusion, and lighting conditions from the perspective of drones still bring great challenges to research in this field. Based on the above problems, this paper proposes an aerial image detection model with excellent performance and strong robustness. First, in view of the common problem that small targets in aerial images are prone to misdetection and missed detection, the idea of Bi-PAN-FPN is introduced to improve the neck part in YOLOv8-s. By fully considering and reusing multiscale features, a more advanced and complete feature fusion process is achieved while maintaining the parameter cost as much as possible. Second, the GhostblockV2 structure is used in the backbone of the benchmark model to replace part of the C2f module, which suppresses information loss during long-distance feature transmission while significantly reducing the number of model parameters; finally, WiseIoU loss is used as bounding box regression loss, combined with a dynamic nonmonotonic focusing mechanism, and the quality of anchor boxes is evaluated by using “outlier” so that the detector takes into account different quality anchor boxes to improve the overall performance of the detection task. The algorithm’s performance is compared and evaluated on the VisDrone2019 dataset, which is widely used worldwide, and a detailed ablation experiment, contrast experiment, interpretability experiment, and self-built dataset experiment are designed to verify the effectiveness and feasibility of the proposed model. The results show that the proposed aerial image detection model has achieved obvious results and advantages in various experiments, which provides a new idea for the deployment of deep learning in the field of UAV multitarget detection.

ObjectiveTuberous sclerosis complex (TSC) is a rare disease with a high risk of epilepsy and cognitive impairment in children. Ketogenic diet (KD) therapy has been consistently reported to be beneficial to TSC patients. In this study, we aimed to investigate the efficacy and safety of KD in the treatment of drug-resistant epilepsy and cognitive impairment in children with TSC.MethodsIn this multicenter study, 53 children (33 males and 20 females) with drug-resistant epilepsy or cognitive impairment caused by TSC were retrospectively recruited from 10 hospitals from January 1, 2010, to December 31, 2020. Intention-to-treat analysis was used to evaluate seizure reduction and cognition improvement as outcomes after KD therapy.ResultsOf the 53 TSC patients included, 51 failed to be seizure-free with an average of 5.0 (range, 4–6) different anti-seizure medications (ASMs), before KD therapy. Although the other two patients achieved seizure freedom before KD, they still showed psychomotor development delay and electroencephalogram (EEG) abnormalities. At 1, 3, 6, and 12 months after the KD therapy, 51 (100%), 46 (90.2%), 35 (68.6%), and 16 patients (31.4%) remained on the diet therapy, respectively. At these time points, there were 26 (51.0%), 24 (47.1%), 22 (43.1%) and 13 patients (25.5%) having ≥50% reductions in seizure, including 11 (21.6%), 12 (23.5%), 9 (17.6%) and 3 patients (5.9%) achieving seizure freedom. In addition, of 51 patients with psychomotor retardation, 36 (36 of 51, 70.6%) showed cognitive and behavioral improvements. During the KD therapy, no serious side effects occurred in any patient. The most common side effects were gastrointestinal disturbance (20 of 53, 37.7%) and hyperlipidemia (6 of 53, 11.3%). The side effects were gradually relieved after adjustment of the ketogenic ratio and symptomatic treatment.ConclusionKD is an effective and safe treatment for TSC-related drug-resistant epilepsy and cognitive impairment in children. KD can reduce seizure frequency and may potentially improve cognition and behavior.

Objective: This study aimed to investigate the emotion regulation effect of Baduanjin Qigong on college students. Methods: The late positive potential (LPP) components were recorded while performing emotional pictures from 12 college students with Baduanjin Qigong experience and 12 with no experience of any mind–body exercises. Results: Under positive emotional stimuli, greater LPP amplitudes were observed in the experimental group in the frontal, central, and temporal areas than in the control group. Under negative emotional stimuli, greater LPP amplitudes were found in the experimental group in the prefrontal area and smaller amplitudes in the occipital area than in the control group. Conclusion: The results reveal the emotion regulation effect on the event-related potential of Baduanjin Qigong to college students. The findings suggest that the regulatory effect of Baduanjin Qigong on emotional stimulation may be a possible reason for reducing the symptoms of depression and anxiety.

A fast robot sorting method based on lightweight convolutional neural network was proposed to improve the recognition speed and environmental adaptability,especially for sorting complex objects.Firstly,the MobileNet-SSD algorithm was used to detect and classify the objects based on lightweight convolutional neural network.Secondly,image preprocessing and edge extraction were used to revise the object locations according to the above object detection results.The sorting experiments on PROBOT Anno robot arm show that the proposed method can achieve fast detection and location for complex objects.Compared with traditional image processing methods,the proposed method is robust to the diversity of target morphology and environment.

Background and ObjectiveHepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and the DNA polymerase delta (POLD) family is significantly related to cancer prognosis. This study aimed to explore the significance of the POLD family in HCC via the DNA damage repair (DDR) pathway.MethodsData mining was conducted using bioinformatics methods. RNA sequencing and clinicopathological data were collected from The Cancer Genome Atlas, GTEx database and the Gumz Renal cohort. Statistical analyses were also performed in cancer samples (n>12,000) and the Affiliated Hospital of Youjiang Medical University for Nationalities (AHYMUN, n=107) cohort.ResultsThe POLD family (POLD1–4) was identified as the most important functional component of the DDR pathway. Based on the analysis of independent cohorts, we found significantly elevated POLD expression in HCC compared with normal tissues. Second, we investigated the prognostic implication of elevated POLD1 expression in HCC and pan-cancers, revealing that increased POLD1 levels were correlated to worse prognoses for HCC patients. Additionally, we identified 11 hub proteins interacting closely with POLD proteins in base excision repair, protein-DNA complex and mismatch repair signaling pathways. Moreover, POLD1 mutation functioned as an independent biomarker to predict the benefit of targeted treatment. Importantly, POLD1 expression was associated with immune checkpoint molecules, including CD274, CD80, CD86, CTLA4, PDCD1 and TCGIT, and facilitated an immune-excluded tumor microenvironment. Additionally, we confirmed that elevated POLD1 expression was closely correlated with the aggressive progression and poor prognosis of HCC in the real-world AHYMUN cohort.ConclusionWe identified a significant association between elevated POLD1 expression and poor patient survival and immune-excluded tumor microenvironment of HCC. Together, these findings indicate that POLD1 provides a valuable biomarker to guide the molecular diagnosis and development of novel targeted therapeutic strategies for HCC patients.

Supervised machine learning is an essential but difficult to use approach in biomedical data analysis. The Galaxy-ML toolkit (https://galaxyproject.org/community/machine-learning/) makes supervised machine learning more accessible to biomedical scientists by enabling them to perform end-to-end reproducible machine learning analyses at large scale using only a web browser. Galaxy-ML extends Galaxy (https://galaxyproject.org), a biomedical computational workbench used by tens of thousands of scientists across the world, with a suite of tools for all aspects of supervised machine learning.

Abstract Background Intellectual disability/developmental delay is a complex condition with extraordinary heterogeneity. A large proportion of patients lacks a specific diagnosis. Next generation sequencing, enabling identification of genetic variations in multiple genes, has become an efficient strategy for genetic analysis in intellectual disability/developmental delay. Methods Clinical data of 112 Chinese families with unexplained intellectual disability/developmental delay was collected. Targeted next generation sequencing of 454 genes related to intellectual disability/developmental delay was performed for all 112 index patients. Patients with promising variants and their other family members underwent Sanger sequencing to validate the authenticity and segregation of the variants. Results Fourteen promising variants in genes EFNB1, MECP2, ATRX, NAA10, ANKRD11, DHCR7, LAMA1, NFIX, UBE3A, ARID1B and PTPRD were identified in 11 of 112 patients (11/112, 9.82%). Of 14 variants, eight arose de novo, and 13 are novel. Nine patients (9/112, 8.03%) got definite molecular diagnoses. It is the first time to report variants in EFNB1, NAA10, DHCR7, LAMA1 and NFIX in Chinese intellectual disability/developmental delay patients and first report about variants in NAA10 and LAMA1 in affected individuals of Asian ancestry. Conclusions Targeted next generation sequencing of 454 genes is an effective test strategy for patients with unexplained intellectual disability/developmental delay. Genetic heterogenicity is significant in this Chinese cohort and de novo variants play an important role in the diagnosis. Findings of this study further delineate the corresponding phenotypes, expand the mutation spectrum and support the involvement of PTPRD in the disease.

Abstract Background Brown-Vialetto-Van Laere Syndrome (BVVLS), a rare neurological disorder characterized by motor, sensory, and cranial neuronopathies, is mainly associated with defective riboflavin transporters encoded by SLC52A2 and SLC52A3 genes. Clinical outcomes have been shown to be improved significantly by high-dose riboflavin supplementation. The aim of this study was to identify genetic causes and further evaluate the clinical course and response to riboflavin in a Chinese pedigree with BVVLS. Case presentation We report the novel compound heterozygous variants c.1328G>A p.(Cys443Tyr) and c.1022_1023insC p. (Leu341Profs*103) of SLC52A2 gene in a female proband who presented in our out-patient clinic at the age of one-year-old with progressive mental and motor regression, breath holding, and brain stem dysfunction including facial weakness, hearing loss, dysphagia. Following high-dose riboflavin supplementation, the respiratory insufficiency and mental, motor, and bulbar function improved. However, sensorineural hearing loss was not improved. The missense variant site was highly conserved. Both variants were not found in the population database gnomAD. The two variants were inherited from her mother and father, respectively. Both variants were predicted to be deleterious by Polyphen2, Mutation taster, and SIFT and were classified as likely pathogenic according to the ACMG guideline. Conclusions Two novel pathogenic variations of SLC52A2 gene were firstly found from a Chinese pedigree with BVVLS. Clinical outcomes could be improved by early diagnosis and riboflavin supplementation.

Campylobacter jejuni is a major foodborne pathogen and can be transmitted to human beings via the consumption of poultry products. This study aimed to determine antibiotic resistance and virulence potential of one hundred C. jejuni isolates from poultry meat and to explore the correlation between them and the multilocus sequence types (MLST). A total of 29 STs and 13 CCs were identified by MLST, of which 8 STs were first identified. The dominant ST was ST583 (21%), followed by ST42 (15%), ST61 (12%), and ST2276 (10%). Eighty-eight isolates showed resistance to at least one antibiotic. The resistance rate to fluoroquinolones was the highest (81%), followed by tetracycline (59%), whereas all the isolates were susceptible to erythromycin and telithromycin. Multi-antibiotic resistance was detected in 18 C. jejuni isolates. Great variability in the adhesion and invasion ability to Caco-2 cells was observed for the 100 isolates, with adhesion rates varying between 0.02% and 28.48%, and invasion rates varied from 0 to 6.26%. A correlation between STs and antibiotic resistance or virulence was observed. The ST61 isolates were significantly sensitive to CIP, while the TET resistance was significantly associated with ST354 and ST6175 complex. ST11326 showed substantially higher resistance to gentamicin and higher adhesion and invasion abilities to Caco-2 cells. The results helped improve our understanding of the potential hazard of different genotypes C. jejuni and provided critical information for the risk assessment of campylobacteriosis infection.

The flow and performance of a rotor of a Savonius hydraulic turbine provided with a shield plate were analyzed by the two-dimensional simulations. The rotor diameter DR is 142 mm, and the Reynolds number based on the velocity of the main flow U0, U0DR/ν, is 1.1×105. The shield plate with a length of 0.5DR is installed upstream of the rotor, perpendicular to the main flow. The comparative experimental studies have visualized the flow and clarified that the shield plate increases the power output of the rotor. The vortex in cell method combined with the volume penalization method was applied to the flow simulation, and the torque acting on the rotor was computed with a custom method by the authors. The simulated flows around the shield plate and rotor agreed with the experimentally visualized ones. The simulation successfully revealed the effect of the shield plate on the flow and power output of the rotor. These demonstrate the applicability of the present simulation method for the performance prediction of the rotor of Savonius hydraulic turbines provided with a shield plate.

Background: Several studies have reported that mindfulness meditation has a potential effect in controlling headaches, such as migraine and tension-type headache; however, its role remains controversial. This review assessed the evidence regarding the effects of mindfulness meditation for primary headache pain. Methods: Only English databases (PubMed, Cochrane Central Register of Controlled Trials [the Cochrane Library], PsycINFO, Psychology and behavioral science collection, PsyArticles, Web of Science, and Scopus) were searched from their inception to November 2016 with the keywords (“meditation” or “mindfulness” or “vipassana” or “dzogchen” or “zen” or “integrative body-mind training” or “IBMT” or “mindfulness-based stress reduction” or “MBSR” or “mindfulness-based cognitive therapy” or “MBCT” and “Headache” or “Head pain” or “Cephalodynia” or “Cephalalgia” or “Hemicrania” or “Migraine”). Titles, abstracts, and full-text articles were screened against study inclusion criteria: controlled trials of structured meditation programs for adult patients with primary headache pain. The quality of studies included in the meta-analysis was assessed with the Yates Quality Rating Scale. The meta-analysis was conducted with Revman 5.3. Results: Ten randomized controlled trials and one controlled clinical trial with a combined study population of 315 patients were included in the study. When compared to control group data, mindfulness meditation induced significant improvement in pain intensity (standardized mean difference, −0.89; 95% confidence interval, −1.63 to −0.15; P = 0.02) and headache frequency (−0.67; −1.24 to −0.10; P = 0.02). In a subgroup analysis of different meditation forms, mindfulness-based stress reduction displayed a significant positive influence on pain intensity (P < 0.000). Moreover, 8-week intervention had a significant positive effect (P < 0.000). Conclusions: Mindfulness meditation may reduce pain intensity and is a promising treatment option for patients. Clinicians may consider mindfulness meditation as a viable complementary and alternative medical option for primary headache.

The Shanghai soft X-ray Free-Electron Laser facility (SXFEL), which is the first X-ray FEL facility in China, is being constructed in two phases: the test facility (SXFEL-TF) and the user facility (SXFEL-UF). The test facility was initiated in 2006 and funded in 2014. The commissioning of the test facility was finished in 2020. The user facility was funded in 2016 to upgrade the accelerator energy and build two undulator lines with five experimental end-stations. The output photon energy of the user facility will cover the whole water window range. This paper presents an overview of the SXFEL facility, including considerations of the upgrade, layout and design, construction status, commissioning progress and future plans.

Photocathodes based on bialkali antimonides have great potential in the field of high-brightness electron sources. In this paper, the influence of incident light absorption on the performance of K_{2}CsSb photocathodes was studied using Monte Carlo simulations. The surface plasmon polaritons (SPPs) were first introduced into K_{2}CsSb photocathodes employing a nanopattern structure to improve the effective absorption of incident light and adjust the initial distribution of the photoelectrons. To evaluate the effect of SPPs on the photocathode performance, photoemission from such photocathodes was modeled using Monte Carlo simulations. Simulations show the quantum efficiency of the K_{2}CsSb photocathode increases by 2–3 times that of the photocathode without SPPs. Moreover, the thermal emittance of the photocathode remains unchanged. These results are crucial to the future development of high-brightness electron beams.

The author wishes to make the following corrections to this paper [...]

The most commonly studied prokaryotic sensory signal transduction systems include the one-component systems, phosphosignaling systems, extracytoplasmic function (ECF) sigma factor systems, and the various types of second messenger systems. Recently, we described the regulatory role of two separate sensory systems in Streptococcus mutans that jointly control bacteriocin gene expression, natural competence development, as well as a cell death pathway, yet they do not function via any of the currently recognized signal transduction paradigms. These systems, which we refer to as LytTR Regulatory Systems (LRS), minimally consist of two proteins, a transcription regulator from the LytTR Family and a transmembrane protein inhibitor of this transcription regulator. Here, we provide evidence suggesting that LRS are a unique uncharacterized class of prokaryotic sensory system. LRS exist in a basal inactive state. However, when LRS membrane inhibitor proteins are inactivated, an autoregulatory positive feedback loop is triggered due to LRS regulator protein interactions with direct repeat sequences located just upstream of the -35 sequences of LRS operon promoters. Uncharacterized LRS operons are widely encoded by a vast array of Gram positive and Gram negative bacteria as well as some archaea. These operons also contain unique direct repeat sequences immediately upstream of their operon promoters indicating that positive feedback autoregulation is a globally conserved feature of LRS. Despite the surprisingly widespread occurrence of LRS operons, the only characterized examples are those of S. mutans. Therefore, the current study provides a useful roadmap to investigate LRS function in the numerous other LRS-encoding organisms.

DEFA1/DEFA3, genes encoding human neutrophil peptides (HNP) 1–3, display wide-ranging copy number variations (CNVs) and is functionally associated with innate immunity and infections. To identify potential associations between DEFA1/DEFA3 CNV and hospital-acquired infections (HAIs), we enrolled 106 patients with HAIs and 109 controls in the intensive care unit (ICU) and examined their DEFA1/DEFA3 CNVs. DEFA1/DEFA3 copy number ranged from 2 to 16 per diploid genome in all 215 critically ill patients, with a median of 7 copies. In HAIs, DEFA1/DEFA3 CNV varied from 2 to 12 with a median of 6, which was significantly lower than that in controls (2 to 16 with a median of 8, p=0.017). Patients with lower DEFA1/DEFA3 copy number (CNV

Hypomyelinating disorders are a group of clinically and genetically heterogeneous diseases characterized by neurological deterioration with hypomyelination visible on brain MRI scans. This study was aimed to clarify the clinical and genetic features of HMDs in Chinese population.119 patients with hypomyelinating disorders in Chinese population were enrolled and evaluated based on their history, clinical manifestation, laboratory examinations, series of brain MRI with follow-up, genetic etiological tests including chromosomal analysis, multiplex ligation probe amplification, Sanger sequencing, targeted enrichment-based next-generation sequencing and whole exome sequencing.Clinical and genetic features of hypomyelinating disorders were revealed. Nine different hypomyelinating disorders were identified in 119 patients: Pelizaeus-Merzbacher disease (94, 79%), Pelizaeus-Merzbacher-like disease (10, 8%), hypomyelination with atrophy of the basal ganglia and cerebellum (3, 3%), GM1 gangliosidosis (5, 4%), GM2 gangliosidosis (3, 3%), trichothiodystrophy (1, 1%), Pol III-related leukodystrophy (1, 1%), hypomyelinating leukodystrophy type 9 (1, 1%), and chromosome 18q deletion syndrome (1, 1%). Of the sample, 94% (112/119) of the patients were genetically diagnosed, including 111 with mutations distributing across 9 genes including PLP1, GJC2, TUBB4A, GLB1, HEXA, HEXB, ERCC2, POLR3A, and RARS and 1 with mosaic chromosomal change of 46, XX,del(18)(q21.3)/46,XX,r(18)(p11.32q21.3)/45,XX,-18. Eighteen novel mutations were discovered. Mutations in POLR3A and RARS were first identified in Chinese patients with Pol III-related leukodystrophy and hypomyelinating leukodystrophy, respectively.This is the first report on clinical and genetic features of hypomyelinating disorders with a large sample of patients in Chinese population, identifying 18 novel mutations especially mutations in POLR3A and RARS in Chinese patients, expanding clinical and genetic spectrums of hypomyelinating disorders.

Objective. Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA) that leads to severe physiologic and developmental problems. Our study is aimed at elucidating the clinical and genetic characteristics of Chinese MLD patients. Methods. Clinical data of 21 MLD patients was collected. All coding exons of ARSA and their flanking intronic sequences were amplified by polymerase chain reaction and subjected to direct sequencing. Results. All 21 patients were diagnosed with MLD clinically and genetically, out of which 17 patients were late infantile and 4 were juvenile types. A total of 34 ARSA mutations, including 28 novel mutations (22 missense, 1 splicing, 1 nonsense, 3 small insertions, and 1 small deletion mutation) and 6 known mutations (5 missense and 1 small insertion mutation), were identified. Prenatal diagnosis was performed for four pedigrees. One fetus was a patient, two fetuses were carriers, and two were wild type. Conclusions. The present study discovered 28 novel ARSA mutations and widely expanded the mutation spectrum of ARSA. Four successful prenatal diagnoses provided critical information for MLD families.

To evaluate the prognostic value of OCT4 expression and vasculogenic mimicry (VM) in human breast cancer, we examined OCT4 expression and VM formation using immunohistochemistry and CD31/PAS (periodic acid-schiff) double staining on 90 breast cancer specimens. All patients were followed up for five–149 months following surgery. Survival curves were generated using Kaplan-Meier method. Multivariate analysis was performed using Cox regression model to assess the prognostic values. Results showed positive correlation between OCT4 expression and VM formation (p < 0.05). Both OCT4 expression and VM were also positively correlated with lymph node metastasis, higher histological grade, and Nottingham prognostic index (p < 0.05). Patients with OCT4 expression or VM formation exhibited poorer overall survival (OS) and disease-free survival (DFS) than OCT4-negative or VM-negative patients (p < 0.05). OCT4-positive/VM-positive patients also had the worst OS and DFS (p < 0.05). In multivariate survival analysis, VM, Nottingham prognostic index (NPI), and Her2 were independent prognostic factors related to OS and OCT4-positive/VM-positive patients, whereas NPI and Her2 were independent predictors of DFS. These results suggest that a combined OCT4 expression/VM could improve the prognostic judgment for breast cancer patients.

The echo-enabled harmonic generation (EEHG) scheme holds promising prospects for efficiently generating intense coherent radiation at very high harmonics of a conventional ultraviolet seed laser. We report the lasing of the EEHG free-electron laser (FEL) at an extreme ultraviolet (EUV) wavelength with a seeded FEL facility, the Shanghai soft x-ray FEL. For the first time, we have benchmarked the basic theory of EEHG by measuring the bunching factor distributions over one octave down to the EUV region. Our results demonstrated the key advantages of the EEHG FEL, i.e., generation of very high harmonics with a small laser-induced energy spread and insensitivity to beam imperfections, and marks a great step towards fully coherent x rays with the EEHG scheme.

OBJECTIVE:Megalencephalic leukoencephalopathy with subcortical cysts (MLC, OMIM 604004) is a rare neurological deterioration disease. We aimed to clarify clinical and genetic features of Chinese MLC patients. METHODS:Clinical information and peripheral venous blood of 20 patients and their families were collected, Sanger-sequencing and Multiple Ligation-dependent Probe Amplification were performed to make genetic analysis. Splicing-site mutation was confirmed with RT-PCR. UPD was detected by haplotype analysis. Follow-up study was performed through telephone for 27 patients. RESULTS:Out of 20 patients, macrocephaly, classic MRI features, motor development delay and cognitive impairment were detected in 20(100%), 20(100%), 17(85%) and 4(20%) patients, respectively. 20(100%) were clinically diagnosed with MLC. 19(95%) were genetically diagnosed with 10 novel mutations in MLC1, MLC1 and GlialCAM mutations were identified in 15 and 4 patients, respectively. Deletion mutation from exon4 to exon9 and a homozygous point mutation due to maternal UPD of chromosome22 in MLC1 were found firstly. c.598-2A>C in MLC1 leads to the skip of exon8. c.772-1G>C in MLC1 accounting for 15.5%(9/58) alleles in Chinese patients might be a founder or a hot-spot mutation. Out of 27 patients in the follow-up study, head circumference was ranged from 56cm to 61cm in patients older than 5yeas old, with a median of 57cm. Motor development delay and cognitive impairment were detected in 22(81.5%) and 5(18.5%) patients, respectively. Motor and cognitive deterioration was found in 5 (18.5%) and 2 patients (7.4%), respectively. Improvements and MRI recovery were first found in Chinese patients. Rate of seizures (45.5%), transient motor retrogress (45.5%) and unconsciousness (13.6%) after head trauma was much higher than that after fever (18.2%, 9.1%, 0%, respectively). SIGNIFICANCE:It's a clinical and genetic analysis and a follow-up study for largest sample of Chinese MLC patients, identifying 10 novel mutations, expanding mutation spectrums and discovering clinical features of Chinese MLC patients.

The Shanghai soft X-ray Free-Electron Laser facility (SXFEL) is being developed in two steps; the SXFEL test facility (SXFEL-TF), and the SXFEL user facility (SXFEL-UF). The SXFEL-TF is a critical development step towards the construction a soft X-ray FEL user facility in China, and is under commissioning at the Shanghai Synchrotron Radiation Facility (SSRF) campus. The test facility is going to generate 8.8 nm FEL radiation using an 840 MeV electron linac passing through the two-stage cascaded HGHG-HGHG or EEHG-HGHG (high-gain harmonic generation, echo-enabled harmonic generation) scheme. The construction of the SXFEL-TF started at the end of 2014. Its accelerator tunnel and klystron gallery were ready for equipment installation in April 2016, and the installation of the SXFEL-TF linac and radiator undulators were completed by the end of 2016. In the meantime, the SXFEL-UF, with a designated wavelength in the water window region, began construction in November 2016. This was based on upgrading the linac energy to 1.5 GeV, and the building of a second undulator line and five experimental end-stations. Construction status and the future plans of the SXFEL are reported in this paper.

The transcription factor Runx2 has been reported to promote epithelial-mesenchymal transition (EMT) in many tumors. Vasculogenic mimicry (VM) is described as the mimicry of endothelial cells by tumor cells to form microvascular tubes in aggressive tumors. Galectin-3 has been reported to regulate cell invasion, migration, and VM formation; it could be regulated by Runx2. However, the relationship between Runx2, Galectin-3, EMT, and VM has not been studied in hepatocellular carcinoma (HCC). We examined Runx2 expression in 89 human HCC samples and found Runx2 expression was associated with VM. Clinical-pathological data analysis revealed that Runx2 expression was associated with a shorter survival period. Overexpression of Runx2 promoted EMT and enhanced cell migration, invasion, and VM formation in HepG2 cells. Conversely, the downregulation of Runx2 inhibited EMT and reduced cell invasion, migration, and VM formation in SMMC7721. Galectin-3 expression declined following the downregulation of Runx2 in HepG2 cells, and increased in SMMC7721 cells after Runx2 knockdown. We consistently demonstrated that the downregulation of LGALS3 in HepG2-Runx2 cells reduced cell migration; invasion and VM formation; while upregulation of LGALS3 in SMMC7721-shRunx2 cells enhanced cell migration, invasion, and VM formation. The results indicate that Runx2 could promote EMT and VM formation in HCC and Galectin-3 might have some function in this process.

The microbunching instability developed during the beam compression process in the linear accelerator (LINAC) of a free-electron laser (FEL) facility has always been a problem that degrades the lasing performance, and even no FEL is able to be produced if the beam quality is destroyed too much by the instability. A common way to suppress the microbunching instability is to introduce extra uncorrelated energy spread by the laser heater that heats the beam through the interaction between the electron and laser beam, as what has been successfully implemented in the Linac Coherent Light Source and Fermi@Elettra. In this paper, a simple and effective scheme is proposed to suppress the microbunching instability by adding two transverse gradient undulators (TGU) before and after the magnetic bunch compressor. The additional uncorrelated energy spread and the density mixing from the transverse spread brought up by the first TGU results in significant suppression of the instability. Meanwhile, the extra slice energy spread and the transverse emittance can also be effectively recovered by the second TGU. The magnitude of the suppression can be easily controlled by varying the strength of the magnetic fields of the TGUs. Theoretical analysis and numerical simulations demonstrate the capability of the proposed technique in the LINAC of an x-ray free-electron laser facility.

Megalencephalic leukoencephalopathy with subcortical cysts (MLC, MIM# 604004) is an autosomal recessive inherited disease mostly resulting from MLC1 mutations. In this study, we finished the functional analysis of MLC1 mutations identified recently in Chinese patients, including five newly described missense mutations (R22Q, A32V, G73E, A275T, Y278H), one known nonsense mutation (Y198X), and two known missense mutations (S69L, T118M). We found MLC1(wt) was localized to the cell periphery, whereas mutant R22Q, A32V, G73E, S69L and T118M were trapped in the lumen of endoplasmic reticulum (ER) when we transfected the wild-type and mutant MLC1 in U373MG cells. Compared to wild type, the mutant G73E, T118M, Y198X and A275T transcript decreased and all mutants except R22Q had lower protein expression in transfected U373MG cells. Therefore, we propose that all these eight MLC1 mutations had functional effect either on their protein/mRNA expression, or on their intracellular protein localization, or both.

In the crystal of the title compound, C15H10N2O3, the molecules are linked together by intermolecular N—H...N hydrogen bonds into chains along the c axis. The crystal structure also shows weak intermolecular C—H...π hydrogen bonds. The three furanyl rings bonded to the imidazole core are not coplanar with the latter; the dihedral angles between the furanyl and imidazole ring planes are 29.3 (2), 19.4 (2), and 4.8 (2)°.

The microbunching instability in the linear accelerator (linac) of a free-electron laser facility has always been a problem that degrades the electron beam quality. In this paper, a quite simple and inexpensive technique is proposed to smooth the electron beam current profile to suppress the instability. By directly adding a short undulator with a transverse gradient field right after the injector to couple the transverse spread into the longitudinal direction, additional density mixing in the electron beam is introduced to smooth the current profile, which results in the reduction of the gain of the microbunching instability. The magnitude of the density mixing can be easily controlled by varying the strength of the undulator magnetic field. Theoretical analysis and numerical simulations demonstrate the capability of the proposed technique in the accelerator of an x-ray free-electron laser.

A new scheme to generate narrow-band tunable terahertz (THz) radiation using a variant of the echo-enabled harmonic generation is analyzed. We show that by using an energy chirped beam, THz density modulation in the beam phase space can be produced with two lasers having the same wavelength. This removes the need for an optical parametric amplifier system to provide a wavelength-tunable laser to vary the central frequency of the THz radiation. The practical feasibility and applications of this scheme are demonstrated numerically with a start-to-end simulation using the beam parameters at the Shanghai Deep Ultraviolet Free-Electron Laser facility (SDUV). The central frequency of the density modulation can be continuously tuned by either varying the chirp of the beam or the momentum compactions of the chicanes. The influence of nonlinear rf chirp and longitudinal space charge effect have also been studied in our article. The methods to generate the THz radiation in SDUV with the new scheme and the estimation of the radiation power are also discussed briefly.