Search

Abstract Background Endometriosis is a common cause of female reproductive problems, and vitamin intake may affect its incidence. Therefore, we further explored the association between multivitamin intake and endometriosis in a large population-based study. Methods This study included 3351 participants from the National Health and Nutrition Examination Survey (NHANES) 1999–2006. The dietary intake of eight vitamins was calculated as the average of two 24-h recall interviews, and information on endometriosis was obtained through questionnaires that included gynecological history. Multiple logistic regression analysis was used to explore the relationship between multivitamin intake and endometriosis. Smoothed curve fitting analysis was employed to assess the dose–response relationship between vitamins and endometriosis. Finally, subgroup analysis and interaction tests were conducted to determine the association of covariates between vitamins and endometriosis. Results In this large-scale cross-sectional study, multiple logistic regression analysis showed that the intake of vitamins A, B1, B2, B6, C and folate was negatively associated with the occurrence of endometriosis. The odds ratios associated with a per-SD increase were 0.836 (95%CI: 0.702, 0.997), 0.817 (95%CI: 0.702, 0.951), 0.860 (95%CI: 0.746, 0.991), 0.784 (95%CI: 0.669, 0.919), 0.845 (95%CI: 0.718, 0.994), and 0.772 (95%CI: 0.660, 0.903), respectively. Smoothed curve fitting analysis revealed that the intake of vitamins A, B1, B2, B6, C, and folate was negatively associated with the risk of endometriosis (P

Abstract Objectives To develop and validate a radiomics nomogram combining radiomics features and clinical factors for preoperative evaluation of Ki-67 expression status and prognostic prediction in clear cell renal cell carcinoma (ccRCC). Methods Two medical centers of 185 ccRCC patients were included, and each of them formed a training group (n = 130) and a validation group (n = 55). The independent predictor of Ki-67 expression status was identified by univariate and multivariate regression, and radiomics features were extracted from the preoperative CT images. The maximum relevance minimum redundancy (mRMR) and the least absolute shrinkage and selection operator algorithm (LASSO) were used to identify the radiomics features that were most relevant for high Ki-67 expression. Subsequently, clinical model, radiomics signature (RS), and radiomics nomogram were established. The performance for prediction of Ki-67 expression status was validated using area under curve (AUC), calibration curve, Delong test, decision curve analysis (DCA). Prognostic prediction was assessed by survival curve and concordance index (C-index). Results Tumour size was the only independent predictor of Ki-67 expression status. Five radiomics features were finally identified to construct the RS (AUC: training group, 0.821; validation group, 0.799). The radiomics nomogram achieved a higher AUC (training group, 0.841; validation group, 0.814) and clinical net benefit. Besides, the radiomics nomogram provided a highest C-index (training group, 0.841; validation group, 0.820) in predicting prognosis for ccRCC patients. Conclusions The radiomics nomogram can accurately predict the Ki-67 expression status and exhibit a great capacity for prognostic prediction in patients with ccRCC and may provide value for tailoring personalized treatment strategies and facilitating comprehensive clinical monitoring for ccRCC patients.

Abstract The pathological role of interferon signaling is emerging in neuroinflammatory disorders, yet, the specific role of Interferon Regulatory Factor 3 (IRF3) in neuroinflammation remains poorly understood. Here, we show that global IRF3 deficiency delays TLR4-mediated signaling in microglia and attenuates the hallmark features of LPS-induced inflammation such as cytokine release, microglial reactivity, astrocyte activation, myeloid cell infiltration, and inflammasome activation. Moreover, expression of a constitutively active IRF3 (S388D/S390D: IRF3-2D) in microglia induces a transcriptional program reminiscent of the Activated Response Microglia and the expression of genes associated with Alzheimer’s disease, notably apolipoprotein-e. Using bulk-RNAseq of IRF3-2D brain myeloid cells, we identified Z-DNA binding protein-1 (ZBP1) as a target of IRF3 that is relevant across various neuroinflammatory disorders. Lastly, we show IRF3 phosphorylation and IRF3-dependent ZBP1 induction in response to Aβ in primary microglia cultures. Together, our results identify IRF3 as an important regulator of LPS and Aβ -mediated neuroinflammatory responses and highlight IRF3 as a central regulator of disease-specific gene activation in different neuroinflammatory diseases.

Urban operations such as counterterrorism, hostage rescue, and building clearance are the primary forms of modern warfare. The large scale of unstructured terrain makes quadruped combat platforms have great military potential and combat effectiveness in modern warfare. To explore the mechanical characteristics and firing disturbances of quadruped combat platforms under multiple shooting modes, the structure of the quadruped combat platform strike system was developed. Then, the rigid–flexible coupling launch dynamics model was built using ANSYS and ADAMS; in addition, simulations under single and continuous shooting modes were conducted by changing loads. According to the dynamic model, the launching process of the quadruped combat platform was simulated, the joint torque characteristics and firing disturbance of the quadruped combat platform were examined, and the method for suppressing the firing disturbance was explored. At last, the quadruped combat platform was confirmed by a live firing experiment in a 100-m indoor shooting range. Findings revealed that the joint torque distribution of the quadruped combat platform presents an uneven trend under static load conditions. The effect of the launching load resulted in a significant torque impact and oscillation to the joint of the quadruped combat platform. Moreover, firing disturbances were produced. Under the single shooting mode, the maximum amplitude of the muzzle center point of the quadruped combat platform along the z-axis direction is 8.42 mm, the maximum amplitude along the y-axis direction is 1.87 mm, and the firing disturbance momentum is 0.39 mm. Under the continuous shooting mode, the impact torque and firing disturbance of the first shooting are near the single shooting mode, whereas the impact torque of the subsequent firing increases by 25.8% compared with the first shooting. Meanwhile, with the superposition effect of the continuous firing vibration, the average firing disturbance also increases to 2.15 mm. Considering the reduction in firing disturbance, the effects of various buffers were discussed. The suppression effect of the unidirectional buffer was found not obvious due to the presence of the impact force during the return and forward processes, whereas the bidirectional buffer with damping can effectively lower the firing disturbance, and its average firing disturbance is 1.02 mm, decreased by 52.56% compared with the rigid connection. The live firing experiment confirmed the possibility of the quadruped combat platform, and the R50 of the platform with a bidirectional buffer was reduced by 47.0% compared with that with a rigid connection, demonstrating its effectiveness in suppressing the firing disturbance and enhancing the firing accuracy.

This paper proposes a multimodal information fusion neural network model that integrates visual, radar, and proprioceptive information. The model uses a spatial crossmodal attention mechanism to fuse the information, allowing the robot to focus on the most relevant information for obstacle avoidance. The attention mechanism enables the robot to selectively focus on the most relevant informative sensory inputs, which improves its ability to navigate complex terrain. The proposed method was evaluated using multiple experiments in challenging simulated environments, and the results showed a significant improvement in the obstacle avoidance success rate. The proposed method uses an actor–critic architecture and a proximal policy optimization (PPO) algorithm to train the robot in a simulated environment. The training process aims to reduce the difference between the robot’s performance in simulated and real-world environments. To achieve this, we randomly adjust the simulation environment’s parameters and add random noise to the robot’s sensory inputs. This approach allows the robot to learn a robust planning strategy that can be deployed in real-world environments. The multimodal information fusion neural network model is designed using a transformer-based architecture. The model shares the encoding of three types of tokens and generates features for the robot’s proprioceptive, visual, and point cloud inputs. The transformer encoder layers are stacked such that the token information from the three modalities can be fuzed at multiple levels. To balance the information from the three modalities, we first separately collect information for each modality and calculate the average value of all tokens from the same modality to obtain a single feature vector. This multimodal information fusion approach improves the robot’s decision-making capabilities in complex environments. The novelty of the proposed method lies in the introduction of a spatial crossmodal attention mechanism that allows the robot to selectively attend to the most informative sensory inputs. This attention mechanism improves the robot’s ability to navigate complex terrain and provides a certain degree of reliability for the quadruped robot in dynamic unknown environments. The combination of multimodal information fusion and attention mechanism enables the robot to adapt better to complex environments, thus improving its obstacle avoidance capabilities. Therefore, the proposed method provides a promising approach for improving the obstacle avoidance capabilities of quadruped robots in complex environments. The proposed method is based on the multimodal information fusion neural network model and spatial crossmodal attention mechanism. The experimental results demonstrate the effectiveness of the proposed method in improving the robot’s obstacle avoidance success rate. Moreover, the potential applications of the proposed method include search and rescue missions, exploration, and surveillance in complex environments.

BackgroundTriglyceride-glucose (TyG) index has been found to be associated with female reproductive disorders, but its relationship with the risk of endometriosis is unknown. Therefore, the aim of this study was to investigate this relationship.MethodsWe performed a two-sample mendelian randomization(MR) analysis to examine the causal effect of TyG index on endometriosis, and inverse variance weighting(IVW) was the main method of analysis. Then, we selected 1484 participants with endometriosis from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2006. Weighted multivariable-adjusted logistic regression and smoothed curve analysis were used to evaluate the correlation between the TyG index and endometriosis.ResultsThe results of MR analysis confirmed that higher TyG index was causally associated with the risk of endometriosis (OR=1.27, 95%CI: 1.05-1.54, P=0.01). In the cross-sectional study, subjects in the highest quartile of TyG index had the highest risk of incident endometriosis after adjusting for covariates(OR = 2.41, 95% CI:1.31-4.44, P for trend

Eccentric training has been proposed as a potential method for enhancing athletes' movement speed. However, a systematic review specifically examining the impact of eccentric training on movement speed in athletes has yet to be conducted. This paper aims to fill this gap by evaluating the effects of eccentric training on movement speed in athletes.A systematic search was carried out on May 15, 2024, in accordance with the PRISMA guidelines for systematic reviews and meta-analyses. The search was conducted across multiple databases, including Web of Science, EBSCOhost, PubMed, CNKI, and VIP, using keywords related to eccentric training, athletes, and movement speed. Out of 421 reviews screened, nine met the inclusion criteria. The quality of the studies was assessed using the PEDro scale, with an average score of 3.67 (range 3–4). The results indicated that short-distance sprint speed (n = 7) was the most affected by eccentric training interventions. Sport-specific movement speed (n = 3) and change of direction speed (COD) (n = 5) were also positively influenced, although to a lesser extent.In conclusion, eccentric training significantly enhances sport-specific movement speed and COD speed, with more moderate effects on short-distance sprinting. These findings suggest that eccentric training can be a valuable intervention for improving movement speed in athletes, especially for sports that involve rapid directional changes.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024547112, identifier CRD42024547112.

BackgroundFibrosis is key in the development and progression of diabetic kidney disease (DKD). Baicalin (BA), wogonin (WGN), and wogonoside (WGS) have renoprotective effects. The mechanism of alleviation of DKD progression, by improving renal fibrosis, is unclear. This study aimed to investigate the mechanisms and effects of a Scutellaria baicalensis Georgi. (Lamiaceae) mixture (MIX, WGN:BA:WGS = 4:2:1) on DKD in a spontaneous DKD model.MethodsMale db/m mice were controls, and db/db mice were diabetes models. Both groups received daily oral gavage of normal saline. Treatment groups received daily oral gavage of BA or MIX (20 mg/kg) for 10 weeks. Biochemical indicators and kidney lesions were assessed. Fibrosis-related proteins were detected by immunoblotting, immunohistochemistry, and real-time fluorescence quantitative PCR.ResultsMIX significantly reduced body weight (40.97 ± 1.43 vs. 42.26 ± 1.60), improved insulin sensitivity (63.70 ± 8.98 vs. 109.48 ± 0.69), lowered the renal hypertrophy index (19.81 ± 2.86 vs. 28.94 ± 0.256), and decreased blood urea nitrogen levels (7.57 ± 0.79 vs. 9.57 ± 0.38) and the urine protein/creatinine ratio (0.50 ± 0.06 vs. 0.80 ± 0.18). MIX also enhanced lipid profiles and renal function by improving renal tubular dilation, restoring renal structures, and reducing glomerulosclerosis, basal membrane thickening, and glycogen deposition. These effects were achieved by reducing the protein and gene expression of collagen II (Col-II), connective tissue growth factor, and collagen I (Col-I).ConclusionMIX inhibits the transforming growth factor-β/Smads signaling pathway, thus alleviating renal fibrosis, and can be used to develop a treatment for DKD.

ABSTRACT Adult severe caries (ASC) brings severe oral dysfunction and treatment difficulties to patients, and yet no clear pathogenic mechanism for it has been found. This study is focused on the composition of dental plaque microbiome profiles in order to identify disease-relevant species and to investigate into their interactions with the S. mutans. Samples of dental plaque were collected for metagenomic analysis. The acidification, aciduricity, oxidative stress tolerance, and gtf (glucosyltransferase) gene expression of S. mutans cocultured with V. parvula which was identified as ASC-related dominant bacterium. The biofilm formation and extracellular exopolysaccharide (EPS) synthesis of dual-strain were analyzed with scanning electron microscopy (SEM), crystal violet (CV) staining, live/dead bacterial staining, and confocal laser scanning microscopy (CLSM). Furthermore, rodent model experiments were performed to validate the in vivo cariogenicity of the dual-species biofilm. The most significantly abundant taxon found associated with ASC was V. parvula. In vitro experiments found that V. parvula can effectively promote S. mutans mature biofilm formation with enhanced acid resistance, hydrogen peroxide detoxicity, and biofilm virulence. Rodent model experiments revealed that V. parvula was incapable of causing disease on its own, but it significantly heightened the biofilm virulence of S. mutans when being co-infected and augmented the progression, quantity, and severity of dental caries. Our findings demonstrated that V. parvula may act as a synergistic pathobiont to modulate the metabolic activity, spatial structure, and pathogenicity of biofilms of S. mutans in the context of ASC.IMPORTANCEAdult severe caries (ASC), as a special type of acute caries, is rarely reported and its worthiness of further study is still in dispute. Yet studies on the etiology of severe caries in adults have not found a clear pathogenic mechanism for it. Knowledge of the oral microbiota is important for the treatment of dental caries. We discovered that the interaction between V. parvula and S. mutans augments the severity of dental caries in vivo, suggesting V. parvula may act as a synergistic pathobiont exacerbating biofilm virulence of S. mutans in ASC. Our findings may improve the understanding of ASC pathogenesis and are likely to provide a basis for planning appropriate therapeutic strategies.

Objective To explore the prognostic impact and clinical application value of therapeutic plasma exchange(TPE) intervention timing and liver injury periodization in patients with exertional heat stroke(EHS). Methods Data of 127 EHS patients from the First Medical Center of the General Hospital of the People′s Liberation Army from January 2011 to December 2023 were collected, then divided into the death group and the survival group based on therapeutic outcomes and into 5 stages according to the dynamic changes of ALT, AST, TBIL and DBIL. According to propensity score matching analysis, 11 patients in the survival group and 12 patients in the death group were included in the statistical analysis, and 20 of them were treated with TPE. The changes in indicators and clinical outcomes before and after TPE were observed, in order to evaluate the impact of intervention timing on prognosis. Results Among the 23 patients, 14 had no liver injury or could progress to the repair phase, resulting in 3 deaths(with the mortality rate of 21.43%), while 9 patients failed to progress to the repair phase, resulting in 9 deaths(with the mortality rate of 100%), with significant differences(P

Objective To review the occurrence of allergic reactions during therapeutic plasma exchange (TPE) and to explore the risk factors of TPE allergic reactions. Methods The clinical data of 929 patients treated with TPE using plasma components by the Department of Transfusion Medicine in our medical center from 2018 to 2023 were collected. The influencing factors of allergic reactions were analyzed by univariate analysis, and the independent risk factors of allergic reactions were analyzed by logistic multivariate regression analysis. Results A total of 4 071 TPEs were performed in 929 patients.Among them, 198 patients (21.31%) experienced 349 times (8.57%) of allergic reactions, with the incidence of grade Ⅰ, Ⅱ and Ⅲ allergic reactions of 16.33%, 81.38% and 2.29%, respectively, and no deaths. The univariate analysis showed that the patient′s age, allergy history, diagnosis of immune-related diseases, ICU admission, plasma consumption, total blood volume, maximum blood flow rate and combined use of albumin were related to the occurrence of allergic reactions (P

Abstract As an innovative technology for enhancing authenticity, security, and risk management, blockchain is being widely adopted in trade and finance systems. The unique capabilities of blockchain, such as immutability and transparency, enable new business models of distributed data storage, point‐to‐point transactions, and decentralized autonomous organizations. Here, the authors focus on blockchain‐based securities trading, in which blockchain technology plays a vital role in financial services as it ultimately lifts trust and frees the need for third‐party verification by using consensus‐based verification. The 12 most popular blockchain platforms are investigated and 6 platforms that are related to finance are elaborated on, seeking to provide a panorama of securities trading practices. Meanwhile, this survey provides a comprehensive summary of blockchain‐based securities trading applications. Numerous practical applications of blockchain‐based securities trading are gathered and they are categorized into four distinct categories. For each category, a typical example is introduced and how blockchain contributes to solving the key problems faced by FinTech companies and researchers explained. Finally, interesting observations are provided ranging from mainstream blockchain‐based financial institutions to security issues of decentralized finance applications, aiming to picture the current blockchain ecosystem in finance.

Abstract T cell receptor (TCR) signaling regulates important developmental transitions, partly through induction of the E protein antagonist, Id3. Although normal γδ T cell development depends on Id3, Id3 deficiency produces different phenotypes in distinct γδ T cell subsets. Here, we show that Id3 deficiency impairs development of the Vγ3+ subset, while markedly enhancing development of NKγδT cells expressing the invariant Vγ1Vδ6.3 TCR. These effects result from Id3 regulating both the generation of the Vγ1Vδ6.3 TCR and its capacity to support development. Indeed, the Trav15 segment, which encodes the Vδ6.3 TCR subunit, is directly bound by E proteins that control its expression. Once expressed, the Vγ1Vδ6.3 TCR specifies the innate-like NKγδT cell fate, even in progenitors beyond the normally permissive perinatal window, and this is enhanced by Id3-deficiency. These data indicate that the paradoxical behavior of NKγδT cells in Id3-deficient mice is determined by its stereotypic Vγ1Vδ6.3 TCR complex.

In urban environment visualization, including both traditional two-dimensional (2D) and three-dimensional (3D) visualization, the height of ground objects results in visual occlusions in ordinary 3D maps, which leads to challenges in displaying spatial relationships. We empirically studied the visual effects of a curled deformation method and assessed whether curled deformation visualization could help participants complete wayfinding tasks. The results revealed that a forward-curled map can include both ego-view and bird-view perspectives, ensure continuity from ego-view to bird-view perspectives, and address foreshortening effects. The remote, distant areas are pulled closer, thereby enhancing the sense of space and allowing participants to better understand the overall situation. A forward-curled map has a wider coverage range of fixation points and a wider scope of visual search and can improve a participant’s task completion efficiency. Moreover, the cognitive burden is not increased with this approach.

Visual localization, a camera pose estimation problem, is a core component of indoor navigation applications. Visual localization methods based on image feature databases or sparse SfM point clouds can provide accurate results but suffer from limitations such as dependency on local feature type and high memory consumption. The state-of-the-art 3D-model-based visual localization methods can overcome these limitations but still meet challenges. It requires expensive specialized equipment (e.g., LiDAR or RGB-D cameras) and complex model optimization to acquire high-precision models as offline maps. The models’ accuracy directly limits visual localization accuracy. Furthermore, the requirement of high-precision models limits the ubiquitous localization of mass users. Therefore, a key problem is whether models reconstructed from mass terminal camera images can achieve localization accuracy close to high-precision models. Model accuracy improvement based on image reconstruction is difficult to break through. Benefiting from the development of neural radiation field rendering technology, improving the accuracy of rendered synthetic images is relatively simple. Based on this idea, we propose a simple and flexible visual localization scheme that enhances visual localization with only imperfect 3D models from a new perspective through neural rendering iterations. In terms of scheme design, it is first proposed to use imperfect 3D models provided by commercial reconstruction algorithms instead of high-precision 3D models to complete visual localization. This idea avoids expensive professional equipment and becomes more universal. In terms of scheme optimization, to bypass the complex model refinement process of commercial 3D models and further improve the initial localization accuracy, the neural rendering iterative improved visual localization (NerfIVL) based method is proposed. This method iteratively updates the pose using the difference between the pixels of the rendered and captured images, allowing for finer localization results. Experimental results performed on 12 sets of datasets from 12Scenes show that our proposed method compares with the localization accuracy of high-precision 3D models reconstructed by professional RGB-D cameras with a difference ranging from only 2.93% to 17.05%, among which the average value for six datasets is less than 8%. This result indicates that comparable visual localization accuracy can be achieved.

BackgroundDepression is increasingly recognized as a factor affecting infertility and the causal relationship between them remains controversial. The aim of this study was to explore the relationship between depression and infertility using Mendelian randomization (MR) and cross-sectional study, and to explore the potential mediating role of obesity.MethodsThe cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) 2013-2018. Multivariable-adjusted logistic regression was used to assess the association between depression and infertility risk, and mediation analysis was to examine the mediating effect of obesity. Then, we performed MR analyses to investigate the causal effect of depression on infertility. Instrumental variables for depression were obtained from a genome-wide association meta-analysis (135,458 cases and 344,901 controls), and summary level data for infertility were obtained from the FinnGen database (6,481 cases and 68,969 controls).ResultsIn the cross-sectional study, a total of 2,915 participants between the ages of 18 and 45 were included, of whom 389 were infertile. We observed that depression was strongly associated with an increased risk of infertility (OR=1.66, 95%CI: 1.19, 2.33), and this relationship remained significant in mild (OR=1.45, 95% CI: 1.09, 1.93), moderate (OR=1.89, 95% CI: 1.26, 2.84), and severe depression (OR=1.74, 95% CI: 1.02, 2.99). Mediation analysis showed that obesity mediated 7.15% and 15.91% of the relationship between depression and infertility for body mass index and waist circumference. Furthermore, depression significantly increased the risk of infertility in both the general obesity (OR=1.81, 95%CI=1.20-2.73, P

Abstract Background Acinetobacter baumannii (A. baumannii) is associated with both hospital-acquired infections (HAP) and community-acquired pneumonia (CAP). In this study, we present a novel CAP-associated A. baumannii (CAP-AB) strain causing severe pneumonia in an afore healthy male patient without underlying conditions. Subsequently, we investigated the pathogenicity and immunogenicity of this CAP-AB strain using a mice pneumonia model. Results A 58-year-old male patient with no underlying conditions experienced worsening symptoms of a productive cough, sputum, and fever that developed acutely, in just 24 h. The diagnosis was severe community-acquired pneumonia (CAP) and type-1 respiratory failure. An A. baumannii strain was isolated from his sputum and blood cultures. To gain a deeper understanding of the rapid progression of its pathology, we utilized the CAP-associated A. baumannii strain YC128, a previously obtained hospital-acquired pneumonia A. baumannii (HAP-AB) strain YC156, and a highly virulent A. baumannii control strain LAC-4 to construct a mouse pneumonia model, and subsequently compared the mortality rate of the three groups. Following inoculation with 107 CFU of A. baumannii, the mortality rate for the YC128, LAC-4, and YC156 groups was 60% (6/10), 30% (3/10), and 0%, respectively. The bacterial burden within the pulmonary, liver, and spleen tissues of mice in the YC128 group was significantly higher than that of the YC156 group, and slightly higher than that of the LAC-4 group. Pathological analysis of lung tissue using HE-staining revealed that the inflammatory pathological changes in mice from the YC128 group were significantly more severe than those in the YC156 group. Additionally, CT scan images displayed more pronounced inflammation in the lungs of mice from the YC128 group compared to the YC156 group. Local levels of cytokines/chemokines such as IL-1β, IL-6, TNF-α, and CXCL1 were assessed via RT-qPCR in lung tissues. In comparison with the YC156 strain, the highly virulent YC128 strain induced the expression of proinflammatory cytokines more rapidly and severely. Furthermore, we examined the in vitro anti-phagocytosis ability of YC128 and YC156 strains against mice peritoneal macrophages, revealing that the highly virulent YC128 isolate displayed greater resistance to macrophage uptake in contrast to YC156. Results from Whole Genome Sequencing (WGS) indicated that YC128 harbored a complete type VI secretion system (T6SS) gene cluster, while YC156 lacked the majority of genes within the T6SS gene cluster. The other virulence-related genes exhibited minimal differences between YC128 and YC156. Drawing from previous studies, we postulated that the T6SS is linked to the hypervirulence and robust anti-phagocytic ability of YC128. Conclusions This article reports on the isolation of a novel hypervirulent CAP-AB strain, YC128, from a severe CAP patient. The results demonstrate that this CAP-AB strain, YC128, is capable of inducing fatal pneumonia and extrapulmonary dissemination in a mouse pneumonia model. Moreover, this highly virulent CAP-AB strain exhibits significantly stronger anti-phagocytic abilities compared to the HAP-AB YC156 strain. Genome sequencing comparisons reveal that the heightened hypervirulence and enhanced anti-phagocytosis abilities observed in YC128 may be attributed to the presence of the T6SS.

Introduction: In solid tumors, regulatory T cell (Treg) and mast cell perform different roles depending on the microenvironment. Nevertheless, mast cell and Treg-mediated interactions in gastric cancer (GC) are unclear, as are their regulation, function, and clinical significance. Objective: The present study demonstrated the mechanism of tumor-infiltrating mast cells stimulating ICOS+ regulatory T cells via the IL-33/IL-2 axis to promote the growth of gastric cancer. Methods: Analyses of 98 patients with GC were conducted to examine mast cell counts, ICOS+ Tregs, and the levels of IL-33 or IL-2. Isolated ICOS+ Treg and CD8+ T cell were stimulated, cultured and tested for their functional abilities in vitro and in vivo. Results: GC patients exhibited a significantly more production of IL-33 in tumors. Mast cell stimulated by tumor-derived IL-33 exhibited a prolonged lifespan through IL-33 mediated inhibition of apoptosis. Moreover, mast cells stimulated by tumor-derived IL-33 secreted IL-2, which induced Treg expansion. These inducible Tregs displayed an activated immunosuppressive phenotype with positive expression for the inducible T cell co-stimulator (ICOS). In vitro, IL-2 from IL to 33-stimulated mast cells induced increased numbers of ICOS+ Tregs with increased immunosuppressive activity against proliferation and effector function of CD8+ T cell. In vivo, ICOS+ Tregs were treated with anti-IL-2 neutralizing antibody followed by co-injection with CD8+ T cells in GC mouse model, which showed an increased CD8+ T cell infiltration and effector molecules production, meanwhile tumor growth and progression were inhibited. Besides, reduction in GC patient survival was associated with tumor-derived ICOS+ Tregs. Conclusion: Our results highlight a crosstalk between GC-infiltrating mast cells and ICOS+ Tregs and provide a novel mechanism describing ICOS+ Treg expansion and induction by an IL-33/mast cell/IL-2 signaling axis in GC, and also provide functional evidence that the modulation of this immunosuppressive pathway can attenuate GC-mediated immune tolerance.

ABSTRACTThe capsule robot has become an important tool in covering the entire spectrum of digestive tract disease diagnosis. To achieve magnetic capsule-robot localization, the Levenberg-Marquardt (LM) algorithm has become a mainstream approach that provides accurate solutions in the general case. In practice, however, to meet the requirements of wearability, fewer sensors and lower power consumption are required. When the number of sensor observations becomes smaller, local convergences and outliers may occur in positioning results. To mitigate this issue, this paper makes two contributions to enhance the robustness of capsule-endoscope positioning, especially when the quality of magnetic observations is low. First, it proposes a two-step approach that initializes the capsule attitude by using inertial measurements before estimating the position. Second, it presents an improved LM-based positioning algorithm based on vest-type magnetic sensor arrays. Furthermore, to verify the proposed approach, a vest-type wearable device with two low-cost magnetometer arrays is designed. Test results have shown the effectiveness of the proposed LM method in enhancing positioning when there is a lack of observations.

Abstract Objective The purpose of this study was to assess the composition of the oral microbial flora of adults with rampant caries in China to provide guidance for treatment. Patients and methods Sixty human salivary and supragingival plaque samples were collected. They were characterized into four groups: patients with rampant caries with Sjogren’s syndrome (RC-SS) or high-sugar diet (RC-HD), common dental caries (DC), and healthy individuals (HP). The 16S rRNA V3-V4 region of the bacterial DNA was detected by Illumina sequencing. PCoA based on OTU with Bray–Curtis algorithm, the abundance of each level, LEfSe analysis, network analysis, and PICRUSt analysis were carried out between the four groups and two sample types. Clinical and demographic data were compared using analysis of variance (ANOVA) or the nonparametric Kruskal–Wallis rank-sum test, depending on the normality of the data, using GraphPad Prism 8 (P

In this study, the effects of applied pressure (0, 90, 120, and 150 MPa) during solidification on the microstructure, mechanical properties, and impact–abrasive wear resistance of Cr-Mn-Mo steel prepared by squeeze casting were systematically investigated. The results demonstrated that the materials produced under pressure showed smaller grains compared to those of the samples fabricated without pressure. Compared to the unpressurized sample, the grain diameter of the sample prepared at 120 MPa decreased by 37.7%, the length of the primary arm shortened by 40.7%, and the spacing of the secondary arm contracted by 14.1%. Furthermore, the impact toughness results indicated that the samples prepared without pressure exhibited brittle fracture characteristics, whereas quasi-destructive fractures predominated in the samples prepared at 120 MPa. Simultaneously, three-point bending strength exhibited a gradual increase with increasing pressure, reaching a maximum value of 855.5 MPa when prepared under 150 MPa. Additionally, the impact–abrasive wear resistance of Cr-Mn-Mo alloyed steel produced by squeeze casting was significantly enhanced compared to the samples produced without pressure. The samples without external pressure exhibited a combination of abrasive and adhesive wear, whereas the wear characteristics of the samples prepared under pressure includes grooves, cutting marks, flaking pits, and accumulating ridges.

AimTimbre in piano performance plays a critical role in enhancing musical expression. However, timbre control in current piano performance education relies mostly on descriptive characterization, which involves large variations of interpretation. The current study aimed to mitigate the limitations by identifying quantitative indices with adequate precision to characterize piano timbre.MethodsA total of 24 sounds of G6 were recorded from 3 grand pianos, by 2 performers, and with 4 repetitions. The sounds were processed and analyzed with audio software for the frequencies and volumes of harmonic series in the spectrum curves. Ten quantitative timbre indices were calculated. Precision validation with statistical gage R&R analysis was conducted to gage the repeatability (between repetitions) and reproducibility (between performers) of the indices. The resultant percentage study variation (%SV) of an index must be ≤10% to be considered acceptable for characterizing piano timbre with enough precision.ResultsOut of the 10 indices, 4 indices had acceptable precision in characterizing piano timbre with %SV ≤10%, including the square sum of relative volume (4.40%), the frequency-weighted arithmetic mean of relative volume (4.29%), the sum of relative volume (3.11%), and the frequency-weighted sum of relative volume (2.09%). The novel indices identified in the current research will provide valuable tools to advance the measurement and communication of timbre and advance music performance education.

This paper examines the chaos caused by introducing advanced language models, specifically ChatGPT, to art. Our focus is on the potential impact of ChatGPT on art creation and collaboration. We explore how it has been utilized to generate art and assist in creative writing and how it facilitates collaboration between artists. This exploration includes an investigation into the use of AI in creating art, music, and literature, emphasizing ChatGPT’s role in generating poetry and prose and its ability to provide valuable suggestions for sentence structure and word choice in creative writing. We conduct case studies and interviews with diverse artists and AI experts to understand the benefits and challenges of using ChatGPT in the creative process. Our findings reveal that artists find ChatGPT helpful in generating new ideas, overcoming creative blocks, and improving the quality of their work. It enables remote collaboration between artists by providing a real-time communication and idea-sharing platform. However, ethical concerns relating to authorship ownership and authenticity have emerged. Artists fear using ChatGPT may lead to losing their artistic identity and ownership of their work. While our data suggests that ChatGPT holds the potential to transform the art world, careful consideration must be given to the ethical implications of AI in art. We recommend future research to focus on developing guidelines for the responsible use of AI in art, safeguarding artists’ rights, and preserving artistic authenticity.

The facultative intracellular bacterium Listeria (L.) monocytogenes may cause severe diseases in humans and animals. The control of listeriosis/L. monocytogenes requires the concerted action of cells of the innate and adaptive immune systems. In this regard, cell-intrinsic immunity of infected cells, activated by the immune responses, is crucial for the control and elimination intracellular L. monocytogenes. Both the immune response against L. monocytogenes and cell intrinsic pathogen control are critically regulated by post-translational modifications exerted by the host ubiquitin system and ubiquitin-like modifiers (Ubls). In this review, we discuss our current understanding of the role of the ubiquitin system and Ubls in listeriosis, as well as future directions of research.

Digestive system diseases, such as gastritis, gastric ulcers, chronic liver disease, inflammatory bowel disease (IBD), and colorectal cancer, represent a major group of diseases that have high morbidity and death rates worldwide. Their incidence continues to rise owing to factors such as dietary structure changes, accelerated lifestyles, increased environmental pollution, and population aging. Despite the rapid development of the medical technology, the treatment of digestive diseases still faces many challenges, such as addressing drug-resistant Helicobacter pylori infections, treating IBD, and improving the efficacy of advanced gastrointestinal tumor therapies. Fortunately, the emergence of drug-releasing materials has provided new insights that can be used in the treatment of digestive disorders. Drug-releasing materials are a category of specially designed carriers or systems capable of carrying drugs and controlling their release at specific time intervals on demand to achieve the desired therapeutic effect. This article reviews recent research progress of drug-releasing materials used to diagnose and treat digestive disorders. First, the limitations of traditional oral drug delivery methods, such as low bioavailability and nonspecific distribution, are discussed. Second, different types of drug-releasing materials, such as liposomes, dendritic polymers, micelles, nanogels, inorganic nanoparticles, and extracellular vesicles, along with their advantages in terms of improved drug stability, biocompatibility, targeting, and controlled release, are outlined. In addition, the application strategies and preclinical findings of various drug release materials for different digestive disorders are discussed in detail. This Review could help researchers explore more advanced nanomaterials for personalized treatment of drug delivery for digestive disorders.

Revealing the plasticity-evolved behaviors is of great significance for developing high-reliability thick Ti–6Al–4V welded joint for deep-sea exploration equipment. This research effort entailed a collaborative utilization of transmission electron microscopy (TEM) and electron backscatter diffraction (EBSD) techniques to reveal the evolution behaviors of microstructure, weld texture, and grain boundaries for thick Ti–6Al–4V laser-arc hybrid welded joint with thickness of up to 40 mm. The discerned outcomes of this study underscored that the mixture strategy of large-sized lath martensite, densely entangled dislocations, and dislocations pile up at grain boundaries in distinct welding layers significantly enlarged the inhomogeneous plasticity of thick Ti–6Al–4V welded joint. Besides, the intensified cylindrical-texture within the weld leads to a substantial augmentation in the occurrence of Schmidt Factor concentrations above 0.3, indicative of a larger fraction of grains assuming a soft-orientation. Furthermore, the investigation unveiled an increase in the proportion of low angle grain boundaries demonstrably augmented the distribution density of geometrically necessary dislocations (GNDs) within the welds, which in conjunction with the enhanced cylindrical texture substantially elevated the grains deformability, consequently reinforcing the plasticity of welded joint. This work has provided insights into the evolution behavior of thick Ti–6Al–4V welded joint for greatly improving the plastic properties of welded structure, and substantially enhancing the service safety for deep-sea exploration equipment.

Abstract Miniaturized fiber-Bragg-grating (FBG) interrogators are of interest for applications in the areas where weight and size controlling is important, e.g., airplanes and aerospace or in-situ monitoring. An ultra-compact high-precision on-chip interrogator is proposed based on a tailored arrayed waveguide grating (AWG) on a silicon-on-insulator (SOI) platform. The on-chip interrogator enables continuous wavelength interrogation from 1 544 nm to 1 568 nm with the wavelength accuracy of less than 1 pm [the root-mean-square error (RMSE) is 0.73 pm] over the whole wavelength range. The chip loss is less than 5 dB. The 1 × 16 AWG is optimized to achieve a large bandwidth and a low noise level at each channel, and the FBG reflection peaks can be detected by multiple output channels of the AWG. The fabricated AWG is utilized to interrogate FBG sensors through the center of gravity (CoG) algorithm. The validation of an on-chip FBG interrogator that works with sub-picometer wavelength accuracy in a broad wavelength range shows large potential for applications in miniaturized fiber optic sensing systems.

Objective This study explores the accuracy of drilling core reorientations by using remanent magnetization. Methods To this end, paleomagnetic analyses were carried out on 43 Silurian sandstone samples collected from five boreholes (TKQ101, SHUN9, TAT19, TZ18, and TS108)in the Tarim Basin. Meanwhile, rock magnetic measurements, scanning electron microscope (SEM) and energy dispersive spectral (EDS) observations were conducted on representative samples to identify the predominant magnetic carriers. Furthermore, the paleocurrent direction inferred from the corrected maximum magnetic susceptibility (Kmax)axis of the anisotropy of magnetic susceptibility (AMS) using remanent magnetization was analyzed. Results AMS results indicate a sedimentary fabric preserved in the studied drilling cores, suggesting their stratigraphy are overall horizontal.Rock magnetic results, SEM and EDS observations reveal that magnetite is the dominant magnetic carrier for the TKQ101 samples, with small amounts of goethite and hematite, while pyrrhotite and magnetite are the dominant magnetic carriers for the other samples. The demagnetization results indicate that the viscous remanent magnetization (VRM) acquired in the present geomagnetic field and the characteristic remanent magnetization(ChRM) of the Silurian formation can be isolated for the TKQ101 samples, where the original azimuth rotations (R, R') estimated by VRM and ChRM are consistent. Furthermore, the paleocurrent direction inferred from the corrected Kmax is supported by the geological evidence, suggesting a counterclockwise rotation of 258.0°-262.0°of the TKQ101 drilling cores. Only one remanence component was isolated for the majority (~90%) of samples from the other four boreholes, which is a superposition component of the VRM acquired in present geomagnetic field and the chemical remagnetization caused by fluid activities, such as oil-gas migration and accumulation, during the Himalayan period. Therefore, it is more reliable to reorient these drill cores by using the VRM component, with confirmation of the paleocurrent direction inferred by the corrected Kmax and geological evidence. Conclusion In summary, to restore the original orientations of these drilling cores, the following rotation angles are required: 258.0°-262.0° counterclockwise rotation for the TKQ101 drill cores; 148.1°, 221.2°, and 318.2° counterclockwise rotation for the 4th, 5th and 6th sections from the borehole SHUN9, respectively; 269.8° and 155.9° counterclockwise rotation for the sections 3 and 5 from the borehole TAT19, respectively; 239.3° and 256.6° counterclockwise rotation for drill cores from the boreholes TS108 and TZ18, respectively.

In ecological modeling, symmetry can manifest in multiple ways, significantly contributing to our understanding of ecosystem stability, species interactions, and ecological balance. Considering the bloom phenomenon caused by excessive algae in ponds and its impact on aquaculture, we establish a class of algae–fish ecological models with two state-dependent impulse controls. In this paper, we first discuss the existence of positive equilibria in the system without impulses. Second, the existence and asymptotic stability of the order-1 and order-2 periodic solutions are analyzed by applying successor functions and a Similar Poincare Criterion. Finally, numerical simulations demonstrate that the model exhibits order-1 and order-2 periodic solutions, clarifying that the system with two impulses can address the problem more effectively.

Most chronic liver diseases progress to liver fibrosis, which, when left untreated, can lead to cirrhosis and hepatocellular carcinoma. MicroRNA (miRNA)-targeted therapeutics have become attractive approaches to treat diseases. In this study, we investigated the therapeutic effect of miR-155 inhibition in the bile duct ligation (BDL) mouse model of liver fibrosis and evaluated the role of miR-155 in chronic liver fibrosis using miR-155-deficient (miR-155 knockout [KO]) mice. We found increased hepatic miR-155 expression in patients with cirrhosis and in the BDL- and CCl4-induced mouse models of liver fibrosis. Liver fibrosis was significantly reduced in miR-155 KO mice after CCl4 administration or BDL. To assess the therapeutic potential of miR-155 inhibition, we administered an rAAV8-anti-miR-155 tough decoy in vivo that significantly reduced liver damage and fibrosis in BDL. BDL-induced protein levels of transforming growth factor β (TGF-β), p-SMAD2/3, and p-STAT3 were attenuated in anti-miR-155-treated compared with control mice. Hepatic stellate cells from miR-155 KO mice showed attenuation in activation and mesenchymal marker expression. In vitro, miR-155 gain- and loss-of-function studies revealed that miR-155 regulates activation of stellate cells partly via STAT3 signaling. Our study suggests that miR-155 is the key regulator of liver fibrosis and might be a potential therapeutic target to attenuate fibrosis progression.

ABSTRACT: Objectives: The emergence of the plasmid-mediated colistin resistance 1 (mcr-1) of Escherichia coli has become a global health concern. This study reports the prevalence of mcr-1 among E. coli isolates from patients with diarrheal disease in Shanghai and the genetic characterization of mcr-1-harbouring plasmids. Methods: A total of 1723 E. coli strains were collected from the faeces of patients with diarrheal disease in all sentinel hospitals in Shanghai from 2016 to 2021. Antimicrobial susceptibility testing was performed by broth microdilution and plasmid conjunction transfer assay was carried out using E. coli C600 as the recipient. The mcr-1-positive E. coli strains (MCRPEC) were subjected to molecular characterization and bioinformatic analysis of the mcr-1-bearing plasmids that they harboured. Results: Only 5 (0.28%) strains were found to harbour the mcr-1 gene using PCR screening. Plasmid conjugation assay and whole-genome sequencing indicated that EC16500, one MCRPEC strain that co-exhibited mcr-1, blaTEM-1, blaOXA-1, qnrS1, qnrS2, arr-3, and catB3, could be conjugated to EC C600 by horizontal transfer with an average efficiency of 3.2 × 10−5. The plasmid pEC16500 harboured similar backbones as p70_2_15, pECGD-8–33, pNCYU-29–19–1_MCR1, and pIBMC_mcr1, and was shown to be encoded within a type IV secretion system (T4SS)-containing 32.6 kbp IncX4, next to the pap2-like membrane-associated gene, to form a 2.4-kb cassette. Furthermore, sequencing and phylogenetic analyses revealed a similarity between other MCR-1-homolog proteins, indicating that the five E. coli isolates were colistin-resistant. Conclusion: Our data represents a significant snapshot of colistin resistance mcr-1 genes and highlights the need to increase active surveillance, especially among children under five years of age, in Shanghai. Great effort needs to be taken to avoid further dissemination of plasmid-mediated colistin resistance among clinically relevant Gram-negative bacterial pathogens.

The ectonucleotidase CD39 has been regarded as a promising immune checkpoint in solid tumors. However, the expression of CD39 by tumor-infiltrating CD8+ T cells as well as their potential roles and clinical implications in human gastric cancer (GC) remain largely unknown. Here, we found that GC-infiltrating CD8+ T cells contained a fraction of CD39hi cells that constituted about 6.6% of total CD8+ T cells in tumors. These CD39hi cells enriched for GC-infiltrating CD8+ T cells with features of exhaustion in transcriptional, phenotypic, metabolic and functional profiles. Additionally, GC-infiltrating CD39hiCD8+ T cells were also identified for tumor-reactive T cells, as these cells expanded in vitro were able to recognize autologous tumor organoids and induced more tumor cell apoptosis than those of expanded their CD39int and CD39-CD8+ counterparts. Furthermore, CD39 enzymatic activity controlled GC-infiltrating CD39hiCD8+ T cell effector function, and blockade of CD39 efficiently enhanced their production of cytokines IFN-γ and TNF-α. Finally, high percentages of GC-infiltrating CD39hiCD8+ T cells correlated with tumor progression and independently predicted patients’ poor overall survival. These findings provide novel insights into the association of CD39 expression level on CD8+ T cells with their features and potential clinical implications in GC, and empowering those exhausted tumor-reactive CD39hiCD8+ T cells through CD39 inhibition to circumvent the suppressor program may be an attractive therapeutic strategy against GC.

Messenger RNA (mRNA) is the molecule which carries genetic information from DNA and guides the synthesis of protein. It participates in many cellular cascades and exhibits substantial associations with certain diseases. The development of advanced approaches for mRNA sensing and imaging is of utmost importance for biological studies and early clinical diagnosis. Herein, a novel fluorescent method is demonstrated for highly sensitive analysis of mRNA based on entropy‐driven strand displacements around three‐dimensional DNA nanostructures. Tetrahedral DNA with four pendant linear sequences provides excellent molecular scaffold loading at multiple sites for target mRNA‐initiated cascade toehold strand displacement reactions. The variations of fluorescence resonance energy transfer states can be used to indicate the presence and level of target mRNA. Besides, MnO2 nanosheets are introduced for intracellular transportation of the reaction system for bioimaging. The operation is relatively simple and the developed approach provides a promising tool for mRNA‐related biological researches and clinical applications.

ABSTRACTLong-term care facilities (LTCFs) for older people play an important and unique role in multidrug-resistant organism transmission. Herein, we investigated the genetic characteristics of mobile colistin resistance gene (mcr-1)-carrying Escherichia coli strains isolated from wastewater of LTCFs in Shanghai. Antimicrobial susceptibility test was carried out by agar dilution methods. Whole-genome sequencing and plasmid sequencing were conducted, and resistance genes and sequence types of colistin in E. coli isolates were analyzed. Core genome multilocus sequence typing (cgMLST) analysis was performed by the Ridom SeqSphere+ software. Phylogenetic tree through the maximum likelihood method was constructed by MEGA X. Out of 306 isolates, only 1 E. coli named ECSJ33 was found, and the plasmid pECSJ33 from ECSJ33 harbored the mcr-1 gene that was located with 59,080 bp belonging to IncI2 type. The plasmid pECSJ33 was capable of conjugation with an efficiency of 2.9 × 10−2. Bioinformatic analysis indicated pECSJ33 shared backbone with the previously reported mcr-1-harboring pHNGDF93 isolated from fish source. Moreover, the cgMLST analysis revealed that ECSJ33 belongs to different lineages from those reported from previous E. coli strains but shared high similarity to NCTC11129 in cluster 11. The phylogenetic tree revealed MCR-1 of ECSJ33 in this study was mostly of animal food origin and that they were closely related. Our study firstly reports detection of genome sequence of a multidrug-resistant mcr-1-harboring E. coli ST155 from wastewater of LTCF source in China. The data may prove that the plasmid pECSJ33 belongs to food origin and help to understand the antimicrobial resistance mechanisms and genomic features of colistin resistance under One Health approach.IMPORTANCEOne Escherichia coli named ECSJ33 was found from wastewater of a long-term care facility (LTCF) and the plasmid pECSJ33 from ECSJ33 harbored the mobile colistin resistance gene (mcr-1) that was located with 59,080 bp belonging to IncI2 type, which was capable of conjugation with an efficiency of 2.9 × 10-2. This paper firstly reports an mcr-1-carrying E. coli strain ST155 isolated from LTCF in China. Comparative genomics analysis indicated pECSJ33 shared backbone with the previously reported mcr-1-harboring pHNGDF93 isolated from fish source. The phylogenetic tree revealed MCR-1 protein of ECSJ33 in this study was mostly of animal food origin and that they were closely related. Therefore, the pECSJ33 could be considered as food-origin transmission mcr-1-harboring plasmid.

Background and aims: Granulocyte colony-stimulating factor (G-CSF) has been proposed as a therapeutic option for patients with ACLF, however clinical outcomes are controversial. We aimed at dissecting the role of G-CSF in an alcohol-induced murine model of ACLF.Methods: ACLF was triggered by a single alcohol binge (5 g/kg) in a bile duct ligation (BDL) liver fibrosis model. A subgroup of mice received two G-CSF (200 μg/kg) or vehicle injections prior to acute decompensation with alcohol. Liver, blood and brain tissues were assessed.Results: Alcohol binge administered to BDL-fibrotic mice resulted in features of ACLF indicated by a significant increase in liver damage and systemic inflammation compared to BDL alone. G-CSF treatment in ACLF mice induced an increase in liver regeneration and neutrophil infiltration in the liver compared to vehicle-treated ACLF mice. Moreover, liver-infiltrating neutrophils in G-CSF-treated mice exhibited an activated phenotype indicated by increased expression of CXC motif chemokine receptor 2, leukotriene B4 receptor 1, and calprotectin. In the liver, G-CSF triggered increased oxidative stress, type I interferon response, extracellular matrix remodeling and inflammasome activation. Circulating IL-1β was also increased after G-CSF treatment. In the cerebellum, G-CSF increased neutrophil infiltration and S100a8/9 expression, induced microglia proliferation and reactive astrocytes, which was accompanied by oxidative stress, and inflammasome activation compared to vehicle-treated ACLF mice.Conclusion: In our novel ACLF model triggered by alcohol binge that mimics ACLF pathophysiology, neutrophil infiltration and S100a8/9 expression in the liver and brain indicate increased tissue damage, accompanied by oxidative stress and inflammasome activation after G-CSF treatment.

Abstract Objective It has been reported that recombinant bovine basic fibroblast growth factor (rbFGF) may possess possible biological functions in promoting the process of wound healing. Consequently, our study aimed to investigate the hemostatic effect of topically applied rbFGF in patients who underwent a loop electrosurgical excision procedure (LEEP). Methods In this retrospective analysis, we meticulously examined clinicopathologic data from a cohort of 90 patients who underwent LEEP at our institution between 2020 and 2021. Subsequently, we conducted inquiries with the patients to ascertain the degree of vaginal bleeding experienced during the postoperative periods of 3 and 6 weeks, comparing it to their preoperative menstrual flow. The magnitude of the menstrual volume alteration was then quantified using a menstrual volume multiplier(MVM). The primary endpoints of our investigation were to assess the hemostatic effect of rbFGF by means of evaluating the MVM. Additionally, the secondary endpoints encompassed the assessment of treatment-related side effects of such as infection and dysmenorrhea. Results Our findings demonstrated a significant reduction in hemorrhage following cervical LEEP. Specifically, in the per-protocol analysis, the study group exhibited a statistically significantly decrease in MVM after 3 weeks (0 [0–0] vs. 1 [0–1], respectively; p

Hg(II), as an extremely hazardous heavy metal contaminant in the environment, poses a significant potential hazard to human health and ecosystems. A GR-MWCNTs-COOH/CeO2/Nafion composite film-modified glassy carbon electrode was prepared using the drop-casting method in this study. The GR-MWCNTs-COOH/CeO2/Nafion/GCE was electrochemically investigated through cyclic voltammetry (CV) and differential pulse stripping voltammetry (DPSV). Additionally, the surface morphologies of the composite film were evaluated using scanning electron microscopy (SEM). The conditions, such as buffer solution, pH, deposition potential, deposition time, modified film thickness, and Nafion content, were optimized. Under optimal experimental conditions, a good linear relationship between the peak current response of Hg(II) and its concentration in the range of 5–100 μg·L−1 was observed, with a detection limit of 0.389 μg·L−1. When it was used to detect Hg(II) in offshore seawater, the recovery rate ranged from 94.72% to 103.8%, with RSDs ≤ 5.79%.

Background: To comprehensively investigate the diagnostic effect of intraoperative indocyanine green (ICG) imaging for endometriosis (EMs). Methods: We systematically retrieved relevant literature from a series of databases (Embase, Web of Science, PubMed, Clinical Trials, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), and WanFang Database) up to January 2024. We also performed manual searches using the reference lists from selected articles, along with reports from relevant meetings and Google Scholar. Data were stored and analyzed by Review Manager version 5.3 and Stata/MP version 14.0. Results: Systematic searches of the literature identified six articles comparing the diagnostic effect of ICG imaging to white light (WL) imaging for EMs during laparoscopic surgery. Two of these studies found that ICG imaging improved the diagnostic rate of EMs while the remaining four studies reported that the diagnostic value of ICG imaging was minimal. Cumulative analysis determined that the sensitivity was 0.88 (95% confidence interval [95% CI]: 0.81–0.93) for WL and 0.64 (95% CI: 0.36–0.84) for ICG. The specificity was 0.85 (95% CI: 0.49–0.97) for WL and 0.88 (95% CI: 0.66–0.97) for ICG. The positive likelihood ratio (LR+) was 5.8 (95% CI: 1.4–24.5) for WL and 5.4 (95% CI: 1.2–24.1) for ICG. The negative likelihood ratio (LR–) was 0.14 (95% CI: 0.09–0.20) for WL and 0.41 (95% CI: 0.18–0.94) for ICG, while the diagnostic odds ratio (DOR) was 42 (95% CI: 10–182) for WL and 13 (95% CI: 1–124) for ICG. Conclusions: Although we only analyzed a limited number of publications, our analysis demonstrated that ICG may be helpful for the visualization of occult EMs, although the diagnostic effect of ICG is not superior to WL. Our findings need to be confirmed by additional studies involving larger sample sizes from multiple centers.

Binge drinking in obese patients positively correlates with accelerated liver damage and liver-related death. However, the underlying mechanism and the effect of alcohol use on the progression of metabolic-dysfunction-associated steatotic liver disease (MASLD) remain unexplored. Here, we show that short-term feeding of a metabolic-dysfunction-associated steatohepatitis (MASH) diet plus daily acute alcohol binges for three days induce liver injury and activation of the NLRP3 inflammasome. We identify that a MASH diet plus acute alcohol binges promote liver inflammation via increased infiltration of monocyte-derived macrophages, neutrophil recruitment, and NET release in the liver. Our results suggest that both monocyte-derived macrophages and neutrophils are activated via NLRP3, while the administration of MCC950, an NLRP3 inhibitor, dampens these effects.In this study, we reveal important intercellular communication between hepatocytes and neutrophils. We discover that the MASH diet plus alcohol induces IL-1β via NLRP3 activation and that IL-1β acts on hepatocytes and promotes the production of CXCL1 and LCN2. In turn, the increase in these neutrophils recruits chemokines and causes further infiltration and activation of neutrophils in the liver. In vivo administration of the NLRP3 inhibitor, MCC950, improves the early phase of MetALD by preventing liver damage, steatosis, inflammation, and immune cells recruitment.

Considering that heavy-metal contamination of seawater is getting worse, building a quick, accurate and portable device for detecting trace zinc in seawater in real time would be very beneficial. In this work, a microfluidic system was developed that includes a planar disc electrode, a micro-cavity for detection, an electrochemical workstation, a computer, a container for waste liquid reprocessing, an external pipeline and other components as well as a graphene/cerium oxide/nano-cerium oxide/Nafion composite membrane was used to modify the planar disc electrode (GR/CeO2/Nafion/Au) to investigate the electrochemical behaviour of Zn(II) using cyclic voltammetry, square-wave voltammetry and orthogonal test methods. Under optimal experimental conditions, the peak reaction current of Zn(II) showed a good linear relationship with the concentration of Zn(II) in the range of 1–900 μg/L with a correlation coefficient of 0.998, and the detection limit of the method was 0.87 μg/L. In addition, the microfluidic system had good stability, reproducibility and anti-interference. The system was used for determining zinc ions in real seawater samples, and the results were very similar to those of inductively coupled plasma–emission spectrometry, demonstrating the practicality of the system for the detection of trace zinc.

Background: The senescence marker protein 30 (SMP30) is a calcium-binding protein whose expression decreases with age, and is closely associated with hepatocellular carcinoma (HCC) development. The primary goal of this study was to examine the mechanistic effect of SMP30 on HCC migration and invasion. Methods: Bioinformatic and immunohistochemical approaches were used to examine the expression of SMP30 in HCC tissues and its relationship to patient survival. We investigated the effects of SMP30 expression on HCC cell proliferation, migration, invasion, and cell cycle dynamics. cDNA microarray technology was used to determine the gene expression profile of SK-Hep-1 cells following recombinant SMP30 overexpression to identify genes downstream of SMP30 that regulate HCC cell migration and invasion. We identified SMP30 interacting proteins by affinity purification-mass spectrometry (AP-MS) and co-immunoprecipitation/western blotting (COIP-WB). Results: SMP30 expression was lower in HCC tissues compared with normal liver tissues, and its expression positively correlated with overall survival in HCC patients. Additionally, SMP30 overexpression effectively blocked the migratory and invasive properties of SK-Hep-1 cells, but did not affect either proliferation rates or cell cycle. cDNA microarray results confirmed that many of the differentially expressed genes identified are involved in the process of epithelial-mesenchymal transition (EMT). AP-MS and COIP-WB experiments confirmed that Rho-associated protein kinase 1 (ROCK1) interacts with SMP30 in SK-Hep-1 cells, and ROCK1 is known to intimately regulate the EMT process. Conclusion: SMP30 inhibits HCC metastasis by influencing the expression of EMT-related proteins after interacting with ROCK1.

Summary: Poor skin wound healing, which is common in patients with diabetes, is related to imbalanced macrophage polarization. Here, we find that nutrition sensor GCN2 (general control nonderepressible 2) and its downstream are significantly upregulated in human skin wound tissue and mouse skin wound macrophages, but skin wound-related GCN2 expression and activity are significantly downregulated by diabetes and hyperglycemia. Using wound healing models of GCN2-deleted mice, bone marrow chimeric mice, and monocyte-transferred mice, we show that GCN2 deletion in macrophages significantly delays skin wound healing compared with wild-type mice by altering M1 and M2a/M2c polarization. Mechanistically, GCN2 inhibits M1 macrophages via OXPHOS-ROS-NF-κB pathway and promotes tissue-repairing M2a/M2c macrophages through eukaryotic translation initiation factor 2 (eIF2α)-hypoxia-inducible factor 1α (HIF1α)-glycolysis pathway. Importantly, local supplementation of GCN2 activator halofuginone efficiently restores wound healing in diabetic mice with re-balancing M1 and M2a/2c polarization. Thus, the decreased macrophage GCN2 expression and activity contribute to poor wound healing in diabetes and targeting GCN2 improves wound healing in diabetes.

Abstract Objectives CD4+ T cell helper and regulatory function in human cancers has been well characterised. However, the definition of tumor‐infiltrating CD4+ T cell exhaustion and how it contributes to the immune response and disease progression in human gastric cancer (GC) remain largely unknown. Methods A total of 128 GC patients were enrolled in the study. The expression of CD39 and PD‐1 on CD4+ T cells in the different samples was analysed by flow cytometry. GC‐infiltrating CD4+ T cell subpopulations based on CD39 expression were phenotypically and functionally assessed. The role of CD39 in the immune response of GC‐infiltrating T cells was investigated by inhibiting CD39 enzymatic activity. Results In comparison with CD4+ T cells from the non‐tumor tissues, significantly more GC‐infiltrating CD4+ T cells expressed CD39. Most GC‐infiltrating CD39+CD4+ T cells exhibited CD45RA−CCR7− effector–memory phenotype expressing more exhaustion‐associated inhibitory molecules and transcription factors and produced less TNF‐α, IFN‐γ and cytolytic molecules than their CD39−CD4+ counterparts. Moreover, ex vivo inhibition of CD39 enzymatic activity enhanced their functional potential reflected by TNF‐α and IFN‐γ production. Finally, increased percentages of GC‐infiltrating CD39+CD4+ T cells were positively associated with disease progression and patients' poorer overall survival. Conclusion Our study demonstrates that CD39 expression defines GC‐infiltrating CD4+ T cell exhaustion and their immunosuppressive function. Targeting CD39 may be a promising therapeutic strategy for treating GC patients.

Helicobacter pylori infection is characterized as progressive processes of bacterial persistence and chronic gastritis with features of infiltration of mononuclear cells more than granulocytes in gastric mucosa. Angiopoietin-like 4 (ANGPTL4) is considered a double-edged sword in inflammation-associated diseases, but its function and clinical relevance in H. pylori-associated pathology are unknown. Here, we demonstrate both pro-colonization and pro-inflammation roles of ANGPTL4 in H. pylori infection. Increased ANGPTL4 in the infected gastric mucosa was produced from gastric epithelial cells (GECs) synergistically induced by H. pylori and IL-17A in a cagA-dependent manner. Human gastric ANGPTL4 correlated with H. pylori colonization and the severity of gastritis, and mouse ANGPTL4 from non-bone marrow-derived cells promoted bacteria colonization and inflammation. Importantly, H. pylori colonization and inflammation were attenuated in Il17a−/−, Angptl4−/−, and Il17a−/−Angptl4−/− mice. Mechanistically, ANGPTL4 bound to integrin αV (ITGAV) on GECs to suppress CXCL1 production by inhibiting ERK, leading to decreased gastric influx of neutrophils, thereby promoting H. pylori colonization; ANGPTL4 also bound to ITGAV on monocytes to promote CCL5 production by activating PI3K–AKT–NF-κB, resulting in increased gastric influx of regulatory CD4+ T cells (Tregs) via CCL5–CCR4-dependent migration. In turn, ANGPTL4 induced Treg proliferation by binding to ITGAV to activate PI3K–AKT–NF-κB, promoting H. pylori-associated gastritis. Overall, we propose a model in which ANGPTL4 collectively ensures H. pylori persistence and promotes gastritis. Efforts to inhibit ANGPTL4-associated pathway may prove valuable strategies in treating H. pylori infection.

Accurate and robust localization is one of the key modules of autonomous driving and multi-sensor robotic systems in complex urban scenes. Compared with camera-based localization, which is sensitive to the influence of light changes caused by different environments, LiDAR-based localization has higher accuracy and robustness. However, the existing LiDAR localization often assumes that the scene is static and ignores the impact of moving objects on localization and mapping. At present, globally consistent multi-sensor localization is an open issue, especially in the complex dynamic environment. We propose a LiDAR-based dynamic scene perception and multi-sensor localization framework. To improve the localization robustness in dynamic complex scenes, we design a moving object segmentation (MOS) module based on spatio-temporal information, and further optimize ground segmentation. On this basis, we design a lightweight, tightly-coupled LiDAR-IMU-GNSS odometry framework, which achieves accurate and real-time position estimation. In the front-end, based on the iterative Extended Kalman filter, we directly register the original 3D point cloud to the map without a feature extractor, which can adapt to different LiDAR scanning patterns, and then can be tightly-coupled with IMU data. Compared with the existing methods, we verify the proposed MOS performance on KITTI datasets, and our approach achieves state-of-the-art performance. In addition, we demonstrate the localization performance of the proposed framework on two public datasets and one solid-state LiDAR dataset. The results show that our system is more accurate than the existing advanced fusion-based localization method.

Introduction This study aimed to evaluate the oncological and prognostic significance of adjuvant chemotherapy (CT) in patients with adult granulosa cell tumors of the ovary (AOGCT). Methods We searched the Chinese National Knowledge Infrastructure, Clinical Trials, Wanfang Database, Web of Science, Cochrane Library, and MEDLINE electronic databases for articles published up to May 2023. Reference lists of the enrolled studies, Google Scholar, and scientific meeting reports were also manually searched. Results We enrolled 5641 patients with AOGCT from 33 eligible studies, including 1674 (29.7%) and 3967 (70.3%) patients in the CT and non-CT groups, respectively. Based on the cumulative results, adjuvant CT did not affect the risk of recurrence or progression (R/P) (odds ratio [OR]: 1.67, 95% confidence interval [CI]: 1.01–2.78, I 2 = 63%, P = .05) and 5-year overall survival (OR: .86, 95% CI: .70–1.04, I 2 = 0%, P = .12) of patients with AOGCT. However, adjuvant CT might reduce the 5-year disease-free survival (OR: 2.90, 95% CI: 1.19–7.08, I 2 = 55%, P = .02). Sub-group analysis revealed that adjuvant CT did not affect the risk of R/P in patients with early-stage AOGCT (OR: .78, 95% CI: .43–1.43, I 2 = 2%, P = .43) and advanced or recurrent AOGCT (OR: .78, 95% CI: .43–1.43, I 2 = 2%, P = .43). Conclusion This meta-analysis suggests that patients with AOGCT might not benefit from adjuvant CT, even those with advanced or recurrent disease. The results should be interpreted with caution because of the inherent limitations of retrospective studies.

Unlike conventional methods of pests control, introducing in an appropriate mathematical model can contribute a batter performance on pests control with higher efficiency while lest damage to ecosystem. To fill the research gap on plant root pest control, we propose a plant root pest management model with state pulse feedback control. Firstly, the stability of the equilibrium point of the model (1.3) is analyzed by using the linear approximate equation, given that the only positive equilibrium point of model (1.3) is globally asymptotically stable. Moreover, the existence and uniqueness of order 1 periodic solutions of model (1.3) are discussed in detail according to the geometric theory of semi-continuous dynamical systems, successor functions method and the qualitative theory of differential equations. Finally, with further analysis in different methods, the asymptotic stability of the order 1 periodic solution of model (1.3) is obtained by using Similar Poincare Criterion or interval set theorem. The results show that this model can effectively control the number of pests below the economic level of damage.

After brain injury, infiltration and abnormal activation of neutrophils damages brain tissue and worsens inflammation, but the mediators that connect activated neutrophils with neuroinflammation have not yet been fully clarified. To identify regulators of neutrophil-mediated neuroinflammation after traumatic brain injury, a mouse model of traumatic brain injury was established by controlled cortical impact. At 7 days post-injury (sub-acute phase), genome-wide transcriptomic data showed that interleukin 17A-associated signaling pathways were markedly upregulated, suggesting that interleukin 17A may be involved in neuroinflammation. Double immunofluorescence staining showed that interleukin 17A was largely secreted by neutrophils rather than by glial cells and neurons. Furthermore, nuclear factor-kappaB and Stat3, both of which are important effectors in interleukin 17A-mediated proinflammatory responses, were significantly activated. Collectively, our findings suggest that neutrophil-derived interleukin 17A participates in neutrophil-mediated neuroinflammation during the subacute phase of traumatic brain injury. Therefore, interleukin 17A may be a promising therapeutic target for traumatic brain injury.

With the development of deep convolutional neural networks, the effect of pedestrian detection has been rapidly improved. However, there are still many problems in small target pedestrian detection, for example noise (such as light) interference, target occlusion, and low detection accuracy. In order to solve the above problems, based on YOLOv4 algorithm, this paper proposes an improved small target pedestrian detection algorithm named PF_YOLOv4. The algorithm is improved in three aspects on the basis of the YOLOv4 algorithm: firstly, a soft thresholding module is added to the residual structure of the backbone network to perform noise reduction process on interference factors, such as light to enhance the robustness of the algorithm; secondly, the depthwise separable convolution replaces the traditional convolution in the YOLOv4 residual structure, to reduce the number of network model parameters; finally, the Convolutional Block Attention Module (CBAM) is added after the output feature map of the backbone network to enhance of the network feature expression. Experimental results show that the PF_YOLOv4 algorithm outperforms most of the state-of-the-art algorithms in detecting small target pedestrians. The mean Average Precision (mAP) of the PF_YOLOv4 algorithm is 2.35% higher than that of the YOLOv4 algorithm and 9.67% higher than that of the YOLOv3 algorithm, while the detection speed is slightly higher than that of YOLOv4 algorithm.

Abstract To improve the accuracy of the Ultra-Wide Band (UWB) based quadrotor aircraft localization, a Finite Impulse Response (FIR) filter aided with an integration of the predictive model and Extreme Learning Machine (ELM) is proposed in this work. The FIR filter estimates the quad-rotor aircraft ’s position by fusing the positions measured with the UWB and Inertial Navigation System respectively. When the UWB dada are unavailable, both the ELM and the predictive model are used to provide the measurements, replacing those unavailable UWB data, for the FIR filter. The ELM estimates the measurement via the mapping between the one step prediction of state vector and the measurement built when the UWB data are available. For the predictive model, we mathematically describe the missing UWB data. Then, both the measurements estimated with the ELM and predictive model are employed to estimate the observations via Mahalanobis distance. The test results show that the FIR filter aided by the predictive model/ELM integrated can reduce the Cumulative Distribution Function and position Root Mean Square Error effectively when the UWB is unavailable. Compared with the ELM assisted FIR filter, the proposed FIR filter can reduce the localization error by about 48.59 %, meanwhile, the integrated method is close to the method with a better solution. Graphical Abstract