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Xiucai Zhang,1 Chao Fang,1 Junfeng Zhang,1 Wang Hua,2 Rong He,1 Mingming Zhou1 1Department of Clinical Laboratory, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, People’s Republic of China; 2Department of Infectious Diseases, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, People’s Republic of ChinaCorrespondence: Mingming Zhou, Department of Clinical Laboratory, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, No. 3333 Binsheng Road, Hangzhou, 310052, People’s Republic of China, Tel +86-571-86670467, Email 6510053@zju.edu.cnBackground: The emergence of carbapenem and colistin co-resistant Escherichia coli poses a huge challenge to infection control. The purpose of this study was to clarify the mechanism of the carbapenems and colistin co-resistance in E. coli strains.Methods: Antimicrobial susceptibility test was carried out by agar dilution methods and colistin resistance was confirmed by broth microdilution methods. Whole genome sequencing was carried out, and resistance genes, sequence types and virulence genes of carbapenems and colistin co-resistance E. coli isolates were analyzed.Results: The results showed that among the 176 carbapenem-resistant Enterobacteriaceae strains, 5 multidrug resistant E. coli strains exhibiting coresistance to carbapenem and colistin. The main mechanism of 5 E. coli strains in this study was generating carbapenem. Four E. coli strains were mcr-positive, while one mcr-negative strain had a new MgrB mutation. The blaNDM-5, blaCTX-M-65, blaOXA-10, blaTEM-1 and mcr-1.1 genes were simultaneously detected in E. coli 20IR1127 strain belonging to ST156 lineage. Other antimicrobial resistance genes encoding aminoglycosides-, sulfonamide-, chloramphenicol-, tetracyclines- and macrolides resistance were also detected.Conclusion: The main mechanisms of carbapenem and colistin resistance were encoded by blaNDM and mcr1.1, meanwhile mgrB mutations also contribute to colistin resistance. To our knowledge, this study is the first to report of E. coli ST156 strain in which the blaNDM-5, blaCTX-M-65, blaOXA-10, blaTEM-1 and mcr1.1 genes coexist. In addition, there is also an E. coli ST457 strain, which carries blaTEM-1, blaNDM-9, blaCTX-M-199 and is positive for mcr1.1 gene.Keywords: Escherichia coli, carbapenem, colistin, co-resistance, WGS

Xiaoyun Gao,* Moxi Chen,* Penghao Liu, Shenyuan Zhou, Sai Kong, Junfeng Zhang, Jun Cao Department of Anesthesiology, Shanghai Sixth People’s Hospital, Shanghai, 200233, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun Cao, Department of Anesthesiology, Shanghai Sixth People’s Hospital, No. 600, Yishan Road, Shanghai, 200233, People’s Republic of China, Tel +86 18930173661, Email dr_caojun@sina.comBackground: A novel ultrasound-guided paravertebral block, the edge laminar block (ELB) was reported recently. However, it was unclear how effective ELB was in comparison with traditional blocking methods. We conducted a trial to compare the analgesic efficacy of ELB with the thoracic paravertebral block (TPVB) and the retrolaminar block (RLB) in patients undergoing video-assisted thoracic surgery (VATS).Methods: We identified 90 patients who were scheduled for VATS and randomly assigned them to three groups: ELB group (Group E), TPVB group (Group T), and RLB group (Group R). Each group underwent ELB, TPVB, and RLB, respectively, under ultrasound guidance before general anesthesia induction. All patients received post-operative routine analgesia protocol. Our primary outcome was the extent of dermatomal sensory loss on the midclavicular, midaxillary, and scapular lines, measured using a pinprick 15 minutes after the nerve block. Secondary outcomes included the intraoperative dose of sufentanil, the numerical rating scale (NRS) scores assessed in the post-anesthesia care unit (PACU) and at 6, 12, and 24 hours post-operatively, and pethidine administrated as analgesic rescue dose.Results: The percentages of nerve block range reaching the midclavicular line, midaxillary line, and scapular line in Group E were 96.7%, 93.3%, 93.3%, and 60% in Group T and 30%, 56.7%, and 96.7% in Group R, respectively. Group E had wider dermatomal sensory loss on the midclavicular line and midaxillary line compared to Group R (P

Additional file 1: Fig. S1. Analysis of biocompatibility of ADNVs. Fig. S2. Effects of different injection routes on biodistribution and tumor control of ADNVs in vivo. Fig. S3. ADNVs promote TAMs polarization towards M1 phenotype. Fig. S4. ADNVs act through TAMs to exert the anti-tumor effect. Fig. S5. The immunoregulatory function of ADNVs is not through TLR2, TLR3, or TLR4 pathway. Tablse S1. Mouse primers for quantitative RT-PCR analysis. Table S2. Plant primers for PCR analysis.

Based on bilinear hardening material model, the swage autofrettage technology of steel sleeve for pump is analyzed. The theoretical calculation formulas of stress, strain, residual stress and strain and punch thrust of swage autofrettage steel sleeve are derived by the elastic-plastic analysis. The accuracy of the theoretical formulas is verified by the swage autofrettage experiment. The result of theoretical calculation is consistent with that of the experiment, and the process of the second loading does not affect the autofrettage result. The theoretical calculation formulas can be used to guide the swage autofrettage technology design of the steel sleeve for the pump.

Colchicine (Col) is used to prevent and treat acute gout flare; however, its therapeutic use is strictly limited owing to severe gastrointestinal side effects after oral administration. Therefore, we developed a dissolvable Col-loaded microneedle (MN) with hyaluronic acid to deliver Col via the transdermal route. We studied the preparation, mechanical properties, skin insertion, skin irritation, drug content, and transdermal release of the Col-loaded MN. The pharmacokinetics of Col after Col-loaded MN application were compared with those of Col solution gavage over 24 h. Knee joint edema evaluation and the hindfoot mechanical threshold test were conducted to determine the pharmacodynamic profile. The dissolvable Col-loaded MN possessed sufficient mechanical strength to penetrate the skin and release the loaded drug. No skin irritation was observed for 3 days after application. We found that 3.36-fold more Col contained in MNs was delivered through the skin compared with that in gel in vitro, and moderate relative bioavailability in vivo. The Col-loaded MN significantly relieved swollen knee joints and mechanical hypernociception in an acute gout model in rats. The dissolvable Col-loaded MN array reduced inflammation and pain via topical administration when acute gout occurred. Reducing the gastrointestinal side effects of Col-loaded MNs is expected to optimize the therapeutic effects of Col and improve patient compliance.

China's social and economic development is currently transitional. There is great incompatibility between the traditional construction land allocation model and the requirements of social and economic development, marked by a prominent contradiction between the supply and demand of construction land that has severely restricted the sustained and healthy development of China's social economy. Improving the efficiency of land resource allocation has become a new driving force for economic growth. With the limited driving power of this factor input for economic development, it is important to explore the occurrence and mechanism of rare construction land resource misallocation to secure the structural benefits of construction land allocation and sustainable economic development, as correcting construction land misallocation would greatly advance land supply-side reform and improve the efficiency of land resource allocation. To explain the mechanism of construction land misallocation, the article builds models for the measurement of both construction land misallocation and its mechanism, applying methods such as spatial autocorrelation model and the spatial Dubin model (SDM). Using these models, we focus on the space-time characteristics, driving factors, and spatial effects of construction land misallocation in China from 2001 to 2016. The sample data in this article come from 235 prefecture-level cities in China. The results show that the misallocation of construction land in China tends to decrease, followed by an increase, with a spatial distribution high in the West and low in the East. There were obvious spatial agglomeration and association features of construction land misallocation and its influencing factors in China, but the spatial correlation effect has weakened. Land financial dependence, industrial structure optimization, and market development have a significant negative impact on construction land misallocation, while government corruption and economic development have a significant positive impact and exert a space spillover effect. We find that the misallocation of construction land in our country is widespread and shows an upward trend. Changing the mode of economic development, increasing government governance, and improving market mechanisms and regional integration can effectively alleviate the misallocation of regional construction land. This paper is significant in discussing the driving factors of construction land misallocation from both theoretical and empirical perspectives, and in analyzing their spatial effect for the first time. It provides research directions and ideas for quantitatively exploring the problem of land resource misallocation, and indicates a feasible way to correct the misallocation of land resources.

Thedatasetcontains waveform data for Back-projection.

Pogostemon cablin (patchouli) is a commercially important medicinal and industrial crop grown worldwide for its medicinal and aromatic properties. Patchoulol and pogostone, derived from the essential oil of patchouli, are considered valuable components in the cosmetic and pharmaceutical industries. Due to its high application value in the clinic and industry, the demand for patchouli is constantly growing. Unfortunately, patchouli cultivation has suffered due to severe continuous cropping obstacles, resulting in a significant decline in yield and quality. Moreover, the physiological and transcriptional changes in patchouli in response to continuous cropping obstacles remain unclear. This has greatly restricted the development of the patchouli industry. To explore the mechanism underlying the rapid response of patchouli roots to continuous cropping stress, integrated analysis of the transcriptome and miRNA profiles of patchouli roots under continuous and noncontinuous cropping conditions in different growth periods was conducted using RNA sequencing (RNA-seq) and miRNA-seq and complemented with physiological data. The physiological and biochemical results showed that continuous cropping significantly inhibited root growth, decreased root activity, and increased the activity of antioxidant enzymes (superoxide dismutase, peroxidase, and catalase) and the levels of osmoregulators (malondialdehyde, soluble protein, soluble sugar, and proline). Subsequently, we found 4,238, 3,494, and 7,290 upregulated and 4,176, 3,202, and 8,599 downregulated differentially expressed genes (DEGs) in the three growth periods of continuously cropped patchouli, many of which were associated with primary carbon and nitrogen metabolism, defense responses, secondary metabolite biosynthesis, and transcription factors. Based on miRNA-seq, 927 known miRNAs and 130 novel miRNAs were identified, among which 67 differentially expressed miRNAs (DEMIs) belonging to 24 miRNA families were induced or repressed by continuous cropping. By combining transcriptome and miRNA profiling, we obtained 47 miRNA-target gene pairs, consisting of 18 DEMIs and 43 DEGs, that likely play important roles in the continuous cropping response of patchouli. The information provided in this study will contribute to clarifying the intricate mechanism underlying the patchouli response to continuous cropping obstacles. In addition, the candidate miRNAs and genes can provide a new strategy for breeding continuous cropping-tolerant patchouli.

Junfeng Zhang,1,2 Meng Wang,1 Baoyu Wei,3 Jiangwei Shi,1 Tao Yu1 1First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300380, People’s Republic of China; 2National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300380, People’s Republic of China; 3State Key Laboratory of Component-based Chinese Medicine, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, People’s Republic of ChinaCorrespondence: Tao Yu, Email doctoryutao@163.comAbstract: The startle reflex is considered a primitive physiological reflex, a defense response that occurs in the organism when the body feels sudden danger and uneasiness, characterized by habituation and sensitization effects, and studies on the startle reflex often deal with pre-pulse inhibition (PPI) and sensorimotor gating. Under physiological conditions, the startle reflex is stable at a certain level, and when the organism is in a pathological state, such as stroke, spinal cord injury, schizophrenia, and other diseases, the reflex undergoes a series of changes, making it closely related to the progress of disease. This paper summarizes the startle reflex in physiological and pathological states by reviewing the databases of PubMed, Web of Science, Cochrane Library, EMBASE, China Biology Medicine, China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodical, Wanfang Data, and identifies and analyzes the startle reflex and excessive startle reaction disorder.Keywords: startle reflex, disease, hyperekplexia, review

Transformers have dominated the field of natural language processing, and recently impacted the computer vision area. In the field of medical image analysis, Transformers have also been successfully applied to full-stack clinical applications, including image synthesis/reconstruction, registration, segmentation, detection, and diagnosis. Our paper aims to promote awareness and application of Transformers in the field of medical image analysis. Specifically, we first overview the core concepts of the attention mechanism built into Transformers and other basic components. Second, we review various Transformer architectures tailored for medical image applications and discuss their limitations. Within this review, we investigate key challenges revolving around the use of Transformers in different learning paradigms, improving the model efficiency, and their coupling with other techniques. We hope this review can give a comprehensive picture of Transformers to the readers in the field of medical image analysis.

Dongjiu Li,1,* Jiayin You,2,* Chengyu Mao,1,* En Zhou,1,* Zhihua Han,1 Junfeng Zhang,1 Tiantian Zhang,1 Changqian Wang1 1Department of Cardiology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People’s Republic of China; 2Department of Emergency, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tiantian Zhang; Changqian Wang, Email ZhangTT2022Dr@163.com; wangcqdr17@163.comObjective: Cardiomyocyte apoptosis critically contributes to ischemia reperfusion injury (IRI), which lacks effective therapeutic strategies. Circular RNAs (circRNAs) serve as novel diagnostic and therapeutic targets in various cardiovascular diseases. CircRNA Fbxl5 is one of the abundantly expressed circRNAs in the heart and its role in myocardial IRI remains elusive.Materials and Methods: Wild-type (WT) mice and neonatal mice ventricular myocytes (NMVMs) were used and subjected to myocardial IRI and anoxia reoxygenation (AR), respectively. Molecular and histological analyses and echocardiography were used to determine the extent of apoptosis, infarct size, and cardiac function.Results: We found that circRNA Fbxl5 was significantly upregulated in the myocardium, as well as in NMVMs subjected to AR. Knockdown of circRNA Fbxl5 ameliorated cardiomyocyte apoptosis, thereby decreasing infarct size and preserving cardiac function. Additionally, in vitro knockdown of circRNA Fbxl5 in NMVMs subjected to AR recapitulated the in vivo findings. Mechanistically, we identified that circRNA Fbxl5 directly sponged and suppressed the endogenous microRNA-146a (miR-146a), thereby weakening its inhibitory effect on MED1, which could further promote the apoptosis of cardiomyocytes.Conclusion: Our findings revealed a novel and critical role for circRNA Fbxl5 in regulating cardiomyocyte apoptosis, and added additional insight into circRNAs mediated during myocardial IRI. The underlying miR-146a-MED1 signaling serves as an important cascade in regulating the apoptosis of cardiomyocytes.Keywords: myocardial ischemia reperfusion injury, circular RNA, microRNA-146a, cardiomyocyte apoptosis

Objective To explore the biological role of copine 8 in the occurrence and progression of pancreatic cancer. Methods GEO datasets were used to compare the expression of copine 8 in pancreatic cancer tissues and adjacent tissues, and TCGA datasets were used to analyze the impact of copine 8 expression on the patients' overall survival rate. The differentially expressed genes between the patients with high and low copine 8 expression were analyzed using GO, KEGG enrichment analysis and gene set enrichment analysis (GSEA). The effect of small interfering RNA-mediated silencing of copine 8 on proliferation, invasion, metastasis, and apoptosis of pancreatic cancer cell lines CFPAC-1 and AsPC-1 were examined using CCK8 assay, colony formation assay, transwell assay, and Annexin V-FITC and propidium iodide staining. The pancreatic cancer transcriptome dataset was analyzed to identify the pathways regulated by copine 8. Results Copine 8 mRNA and protein were highly expressed in pancreatic cancer tissues and lowly expressed in adjacent tissues. Copine 8 expression was significantly correlated with the survival prognosis of the patients with pancreatic cancer (P=0.033). Enrichment analysis showed that copine 8 affected WNT, Hippo, mTOR, and ERBB signaling pathways in pancreatic cancer, and may promote the progression of pancreatic cancer by affecting the expression of the key molecules YAP1, STK3, STK4 and SGMS1 in Hippo pathway. Interference of copine 8 expression significantly suppressed the proliferation, invasion and migration and obviously increased the number of apoptotic cells in 2 pancreatic cancer cell lines. Conclusion Copine 8 has a strong cancer-promoting effect and plays a significant role in the proliferation, invasion, metastasis and apoptosis of pancreatic cancer.

Background Gestational diabetes mellitus (GDM) seriously affects the health of mothers and babies, and there are still no effective early diagnostic markers. Therefore, it is necessary to find diagnostic biomarkers for screening GDM in early pregnancy. Circular RNA (circRNA) is more stable than linear RNA, and can be encapsulated in exosomes and participate in the pathological process of various diseases, which makes it a better candidate biomarker for various diseases. In this study, we attempted to identify the exosomal circRNA biomarkers for detecting early GDM. Methods We performed microarray analysis to compare the plasma exosomal circRNA expression profiles of three GDM patients 48 h before and 48 h after delivery. The repeatability of the expression of circRNAs were randomly validated by RT-PCR analysis. Pearson correlation analysis was applied to evaluate the correlation between circRNAs and OGTT level. ROC curve was established to assess the diagnostic value of circRNAs for GDM at different stages. Results Plasma exosomal hsa_circRNA_0039480 and hsa_circRNA_0026497 were highly expressed in GDM patients before delivery (P P Conclusion Plasma exosomal hsa_cirRNA_0039480 is highly expressed in GDM patients at different stages and may be served as a candidate biomarker for early detection of GDM.

Additional file 1: Supplementary Figure 1. HPLC fingerprint of total Total flavones of Abelmoschus manihot (L.) medicus. 1 Rutin, 2 hyperoside, 3 isoquercetin, 4 Myricetin, 5 quercetin-3���-O-glucoside, 6 quercetin. Supplementary Figure 2. The proportions of dentric cells in BALF. TFA (125, 250, 500 mg/kg) or PBS was gavage daily for 7 days, and PR8 was intranasally administrated at a dose of 5000 TCID50 per mouse (n = 3 mice per group). The proportions of CD11c + dentric cells in BALF were detected by flow cytometry. The value are shown as means �� SD of three individual experiments.

Additional file 1: Figures S1–4.

Additional file 1: Table S1. Population characteristics between those followed up and lost follow-up.

Additional file 2: Table S1. The primer sequences used in this study. Table S2. The antibodies used in this study.

models, experimental setups, and latency comparison

Additional file 1: Supplementary Word 1. h-RHOB 3-UTR reporter vector.

Additional file 6: Table S6. The association between greenness, air pollution with the metabolic biomarkers among the participants with at least one follow-up.

Additional file 2: Supplementary Figure 3. Gels/blots are cropped for the clear presentation of results. Samples derived from the same experiment and gels/blots were processed in parallel. The Uncropped Blot in Fig. 5O. The red arrow indicates the location of target bands. Supplementary Figure 4. Gels/blots are cropped for the clear presentation of results. Samples derived from the same experiment and gels/blots were processed in parallel. The Uncropped Blot in Fig. 6O. The red arrow indicates the location of target bands. Supplementary Figure 5. Gels/blots are cropped for the clear presentation of results. Samples derived from the same experiment and gels/blots were processed in parallel. The Uncropped Blot in Fig. 7J. The red arrow indicates the location of target bands. Supplementary Figure 6. Gels/blots are cropped for the clear presentation of results. Samples derived from the same experiment and gels/blots were processed in parallel. The Uncropped Blot in Fig. 7K. The red arrow indicates the location of target bands.

Additional file 5: Table S5. The association between air pollution with the metabolic biomarkers (One-year and five-year exposure) in the longitudinal analysis.

Additional file 7: Table S7. The association between the greenness and air pollution with the metabolic syndrome and the components (binary outcome) in the longitudinal analysis using the Joint Interim Societies’ definition of MetS for Chinese populations.

Additional file 1: Figure S1. Characterization of cDex and DETA-Dex. Figure S2. Kinetic analysis of the RNA droplets induced by the cationic polymers. Figure S3. Quantification of the transcription levels of common markers by RNA-seq. Figure S4. Gene Set Enrichment Analysis. Figure S5. Evaluation of antitumor activity of the cationic polymers in the BALB/c mouse model and BALB/c nude mouse model. Figure S6. Examples of the gating strategies for intracellular staining flow cytometry analysis. Figure S7. Evaluation of the antitumor activity of the cationic polymer combined with an anti-PD-1 antibody. Table S1. GPC analysis of the cationic polymers. Table S2. Dextran standards for GPC analysis. Table S3. qPCR primers and probes. Table S4. Flow cytometry antibodies.

Additional file 3: Table S3. The association between the greenness and air pollution with the 2012 baseline metabolic biomarkers (binary outcome).

Additional file 2: Table S2. Baseline population characteristics across different counties.

Additional file 1: Supplementary methods. Table S1. Population Characteristics by High and Low PM2.5 and NO2 Exposure Levels (unit: μg/m3). Table S2. Association between NO2, PM2.5 levels and all-cause mortality adjusting for different variables. Table S3. The association between NO2, PM2.5 and mortality stratified by different exposure level groups (unit: μg/m3). Figure S1. The scatter plot of NO2 and PM2.5 of the year closest to outcome assessment. Figure S2. The restricted cubic spline of NO2 and PM2.5 on mortality. Figure S3. DAGs of NO2 and PM2.5 Relationship on Mortality.

Additional file 4: Table S4. The association between the greenness and air pollution with the metabolic biomarkers (continuous outcome) in the longitudinal analysis.

International audience

models, experimental setups, and latency comparison

Lithium–sulfur (Li–S) batteries are considered as a next-generation energy storage solution thanks to the dramatic increase in their energy density and the accompanying low fabrication cost. Nonetheless, their practical applications have been hampered by critical challenges such as cycling instability, low sulfur utilisation and efficiency. Here, the interfacial growth of Ni(OH)2-encapsulated sulfur nanoparticles in a reduced graphene oxide free-standing matrix as Li–S cathodes has been highlighted, along with a detailed application investigation of the sandwich foam structure in Li–S batteries. Compared to sulfur composites based solely on a graphene host (S@rGO), this composite foam cathode could provide significant improvements in specific capacity and long-cycle stability with the effective confinement and promoted conversion of lithium polysulfides. Moreover, the sandwich foam composite cathode exhibits a high specific capacity of 1189 mA h g−1 (0.1 C), better rating performance (691 mA h g−1 at 2 C) and remarkable cycling stability, retaining 81% of the initial capacity after 200 cycles of charge–discharge at 0.2 C. Furthermore, Ni(OH)2 wrapping at the cathode–electrolyte interface offers vastly improved polysulfide shuttle suppression, which provides a new cathode encapsulation method for further developments of advanced Li–S cathodes.

To solve the problems of low detection accuracy, high false positive rate and unbalanced network data sets in the high-dimensional massive data environment of traditional intrusion detection model, an intrusion detection model based on improved Stack autoencoder (SAE) and bidirectional feature attention short-time memory network (BALSTM) is proposed. In the model, firstly, Smote-Tomek combined sampling algorithm is used to reduce the imbalance rate of data sets, and then batch standardization and early stop mechanism are used to improve SAE for feature extraction, which accelerates the convergence speed of the model and solves the over-fitting problem. Finally, an attention module is added to BLSTM, which enables BALSTM model to pay attention to context information and strengthen the learning of important features. Analysis and simulation results show that the model has better performance in accuracy and false alarm rate.

Accurate segmentation of brain tumors from multi-modal Magnetic Resonance (MR) images is essential in brain tumor diagnosis and treatment. However, due to the existence of domain shifts among different modalities, the performance of networks decreases dramatically when training on one modality and performing on another, e.g., train on T1 image while performing on T2 image, which is often required in clinical applications. This also prohibits a network from being trained on labeled data and then transferred to unlabeled data from a different domain. To overcome this, unsupervised domain adaptation (UDA) methods provide effective solutions to alleviate the domain shift between labeled source data and unlabeled target data. In this paper, we propose a novel Bidirectional Global-to-Local (BiGL) adaptation framework under a UDA scheme. Specifically, a bidirectional image synthesis and segmentation module is proposed to segment the brain tumor using the intermediate data distributions generated for the two domains, which includes an image-to-image translator and a shared-weighted segmentation network. Further, a global-to-local consistency learning module is proposed to build robust representation alignments in an integrated way. Extensive experiments on a multi-modal brain MR benchmark dataset demonstrate that the proposed method outperforms several state-of-the-art unsupervised domain adaptation methods by a large margin, while a comprehensive ablation study validates the effectiveness of each key component. The implementation code of our method will be released at \url{https://github.com/KeleiHe/BiGL}.

Objective: To investigate the effect of warm needle moxibustion on patients with lumbar disc herniation (LDH). Methods: A total of 100 patients with lumbar disc herniation treated in our hospital were recruited as the study cohort and randomly assigned into a control group and an observation group. The patients in the control group underwent routine acupuncture treatment, while those in the observation group underwent warm needle moxibustion treatment. The observed indexes, including the clinical efficacy, the visual analogue scale (VAS) scores, the Japanese Orthopedic Association (JOA) scores, the Oswestry disability index (ODI) scores, and the serum inflammatory factor levels were compared between the control group and the observation group. Results: The total cure rate in the observation group was significantly higher than it was in the control group (76.0% vs 92%, P=0.029). Compared with the patients in the control group after the treatment, the patients’ VAS and ODI scores in the observation group were significantly lower, but their JOA scores were significantly higher, and the differences were statistically significant (all P

The digging resistance in a normal state is the key to excavator design and automated excavation. It is difficult to accurately predict, simulate, or directly measure the digging resistance in a normal state due to uncertainties in the soil properties and excavation parameters. In this paper, a research idea is proposed that uses the working device as the entry point to indirectly calculate the digging resistance in a normal state by measuring the motion parameters and the cylinder pressure intensity. Based on the rule of combination for spatial force systems, a method for combining and projecting the system of the digging resistance is proposed in which the system is projected as six parts, and the tangential force, normal force, and bending moment in the plane of symmetry of the working device are the objects of the solution to avoid redundant equations. Based on kinematics and dynamics models of the excavator and the force and moment equilibrium conditions of the working device, equations for the active-side calculation of the incomplete digging resistance are derived. Based on these equations, the motion parameters of the working device and data on the cylinder pressure intensity obtained by measurement are used to calculate the incomplete digging resistance. The validation scheme and process proposed use the incomplete digging resistance as the external load to obtain the simulated stress of the working device through transient analysis. The simulated stress and the measured stress corresponding to the position of the measurement point are extracted and compared. The results show that there is a difference in the size of the numerical value between the simulated and measured stress, but the variation law is highly consistent, which validates the calculation method. In this paper, an active-side calculation method is provided for the incomplete digging resistance in a normal state without considering the soil-tool interaction relationships, which lays a theoretical foundation for the study of the digging resistance characteristics in a normal state, as well as excavator design and automated excavation.

Plant growth regulators (PGRs) are commonly used to regulate maturation in strawberry. Despite this, comprehensive assessments of the metabolomic effects of PGRs on strawberry maturation are lacking. In this study, a nuclear magnetic resonance-based approach, combined with multivariate and pathway analysis, was used to evaluate the regulatory effects of gibberellin, forchlorfenuron, and brassinolide, applied at two different maturation stages, on the expression of metabolites in strawberry. The results demonstrated that the PGRs differentially influenced metabolism, whether applied at the same or different maturation stages. Additionally, we also discovered that these different PGRs exhibited some similar metabolic trends when applied at the same growth period. Our findings validate the use of NMR-based metabolomics for identifying subtle changes in the expression of metabolites associated with PGR application.

The curved beam bridge exhibits lateral displacement during construction and operation. Taking a curved beam bridge as an example, the status of lateral displacement of the bridge is investigated in detail in this paper. To understand the mechanism of the curved beam lateral displacement, further to determine the curved beam lateral displacement under temperature effect, using ANSYS software to establish solid element model of the curved beam, steady state thermal analysis method is applied to analyze temperature field. Based on the analysis, the lateral displacement under temperature effect is analyzed. Then in order to further explain the lateral displacement mechanism, to discuss the frictional force causing the residual deformation of the rubber bearing to make the lateral displacement of the curved beam, the mechanical mechanism of curved beam under temperature effect is approximately analyzed. On the basis of clarifying the mechanism of lateral displacement, the paper puts forward the reinforcement measures for the curved beam bridge. In order to verify the treatment effect, long-term displacement monitoring is performed on the bridge. Numerical studies and monitoring data show that temperature is the main factor that causes the lateral displacement. Monitoring data over the past year shows that the displacement of the bearing is less than the value of allowable displacement after the reinforcement measures are adopted, and the bridge is in a safe state.

International audience; This paper is concerned with the event-triggered positive -gain non-fragile filter design of positive Markov jump systems. By using the upper and lower bounds of the error vector of system measurement outputs, the positive -gain filtering system to be designed is transformed into interval uncertain systems. Combining linear Lyapunov functions and linear programming, the positivity and stability of such systems can be obtained. Then, the proposed approach is developed to investigate positive -gain additive and multiplicative non-fragile filters, respectively. Furthermore, two classes of non-fragile positive filters are proposed for positive Markov jump systems with incomplete measurements and sensors saturation, respectively. Finally, two examples are provided to verify the effectiveness of the proposed design.

Additional file 1: Table S1. Baseline clinical characteristics between non-diabetic (Non-DM) and diabetic (DM) groups.

Additional file 1: File S1. The Sanger sequencing of the linear circ_0004296 RNA sequence carried on the plasmid.

Additional file 1.

Additional file 1: Figure S1. The content of microRNAs in honeysuckle. a The photo of honeysuckle. b The levels of plant microRNAs in honeysuckle. Figure S2. Prediction of the major immune checkpoint genes sequence targeted by miR2911. a–c Schematic description of the base pairing between miR2911 and major immune checkpoint genes (PD-1, PDL-1 and CTLA4; mouse and human), and their binding energies.

In order to improve the prediction accuracy of railway passenger traffic, an ARIMA model and FSVR are combined to propose a hybrid prediction method. The ARIMA prediction model is established based on the known railway passenger traffic data, and then, the ARIMA prediction results are used as the training set of the FSVR method. At the same time, the air price and historical passenger traffic data are introduced to predict the future passenger traffic, to realize the mixed prediction of railway passenger traffic. The case study demonstrates that the hybrid prediction method can effectively improve the prediction performance of railway passenger traffic. Compared with the single ARIMA method, the hybrid prediction method improves the delay of the prediction results. Compared with the FSVR prediction result, the hybrid prediction method greatly reduces the errors in the extreme points of passenger traffic and long-term prediction. The relevant research results of this paper provide a useful reference for the prediction of railway passenger traffic.

Additional file 6: Figure S3. A. Knockdown of EIF4A3 had no effect on circ_0004296 expression. B. The efficiency of ETS1 knockdown at protein level. C. The efficiency of ETS1 overexpression at protein level. D. Colony formation assays were used to measure viability of PCa cells after ETS1 knockdown. E. The migration abilities of PCa cells were analyzed by Transwell assays for migration after ETS1 knockdown. Scale bars =100um. F. Colony formation assays were used to measure viability of PCa cells after ETS1 overexpression. G. The migration abilities of PCa cells were analyzed by Transwell assays for migration after ETS1 overexpression. Scale bars =100um. H. Kaplan-Meier analysis for different ETS1 protein expression in PCa patients. I, J. Luciferase-labeled stably DU145-overexpressing circ_0004296 and luciferase-labeled DU145-vector cells were constructed. Scale bars =200um. *P

Additional file 5: Figure S2. The circ_0004296 knockdown promoted the proliferation, migration, invasion, and EMT induction of PCa cells. A. Schematic illustration of designed siRNAs (siRNA#1, siRNA#2, and siRNA#3) targeting the back-splice junction of circ_0004296. B. The expression of circ_0004296 and ETS1 was detected by qRT-PCR in PC3 and DU145 cells transfected with siRNA-circ_0004296 or si-NC. C, D. CCK8 and colony formation assays were performed to measure the viability of PCa cells after circ_0004296 knockdown. E-H. The migration and invasion abilities of PCa cells were analyzed by wound healing and Transwell assays for migration and invasion after circ_0004296 knockdown. Scale bars =100um. I. Western blotting assay was performed to detected the expression of EMT-related proteins, namely E-cadherin, N-cadherin, Vimentin, and Snail, after circ_0004296 knockdown. J. Protein profiling was used to screen specific proteins bound by circ_0004296 in PCa cells. *P

Forecasting the passenger flow of high speed railway is a hot but difficult research topic in the field of railway transportation for a long time. It is the basis of the revenue management and the rapid response mechanism for the railway sector. With the increasingly fierce competition of aviation and railway, it brings forward new challenges to the forecasting. This paper proposes a new method of passenger flow forecasting of the high speed railway in competitive market based on XGBoost model. The ticket price of the train is also taken into account in the method. First, the flight booking info data is preprocessed and statistics features are calculated to complement the missing data. Then, the railway booking info and flight booking info merge into a large training data and prediction model is constructed by using XGBoost algorithm. Applying this model for prediction, the passenger flow in competitive market can be obtained. Experimental results show that the proposed model has higher prediction accuracy than traditional models.