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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

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.

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.

Abstract Extreme myopia (EM), defined as a spherical equivalent (SE) ≤ −10.00 diopters (D), is one of the leading causes of sight impairment. Known EM-associated variants only explain limited risk and are inadequate for clinical decision-making. To discover risk genes, we performed a whole-exome sequencing (WES) on 449 EM individuals and 9606 controls. We find a significant excess of rare protein-truncating variants (PTVs) in EM cases, enriched in the retrograde vesicle-mediated transport pathway. Employing single-cell RNA-sequencing (scRNA-seq) and a single-cell polygenic burden score (scPBS), we pinpointed PI16 + /SFRP4+ fibroblasts as the most relevant cell type. We observed that KDELR3 is highly expressed in scleral fibroblast and involved in scleral extracellular matrix (ECM) organization. The zebrafish model revealed that kdelr3 downregulation leads to elongated ocular axial length and increased lens diameter. Together, our study provides insight into the genetics of EM in humans and highlights KDELR3’s role in EM pathogenesis.

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.

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

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.

Introduction Elderly patients are at a high risk of postoperative delirium (POD), leading to increased postoperative morbidity and mortality. The use of dexmedetomidine and depth of anaesthesia may influence POD. This study aims to determine the effects of dexmedetomidine infusion versus normal saline placebo during light versus deep anaesthesia on POD among elderly patients undergoing major non-cardiac surgery.Methods and analysis This prospective, multicentre, randomised, controlled, factorial trial will be conducted at three tertiary hospitals in Jiangsu, China. We will recruit a total of 420 patients who are at least 60 years old and undergoing major non-cardiac surgery (thoracic, abdominal, urology, orthopaedic and spine surgery) under general anaesthesia. Patients will be randomised (1:1:1:1) to receive one of four anaesthesia regimens: (1) dexmedetomidine and light anaesthesia, (2) dexmedetomidine and deep anaesthesia, (3) placebo and light anaesthesia or (4) placebo and deep anaesthesia. Dexmedetomidine will be infused at 0.5 µg/kg/h throughout surgery, and intraoperative bispectral index target will be 55 for light anaesthesia and 40 for deep anaesthesia. The primary outcome is the occurrence of POD during the first 7 days postoperatively or until hospital discharge, assessed using the 3-min Confusion Assessment Method two times per day. The secondary outcomes include days with POD, type of POD, pain scores at rest and on movement at 24 and 48 hours postoperatively, patient-controlled intravenous fentanyl consumption during 0–24 and 24–48 hours postoperatively, hypotension, bradycardia, postoperative nausea and vomiting, non-delirium complications, length of postoperative hospital stay, 30-day cognitive function and 30-day mortality. Data will be analysed on a modified intention-to-treat basis.Ethics and dissemination This trial was approved by the Ethics Committee of the First Affiliated Hospital of Soochow University and each participating centre. The trial results will be published in a peer-reviewed journal.Trial registration Chinese Clinical Trial Registry (ChiCTR2300073271)

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.

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.

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.

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.

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.

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

Background: Multimodal analgesia plays a key role in enhanced recovery after surgery. Herein, we describe a trial protocol investigating the effects of oxycodone-vs. sufentanil-based patient-controlled analgesia in combination with quadratus lumborum block (QLB) vs. transverse abdominis plane block (TAPB) on quality of recovery following major laparoscopic gastrointestinal surgery. Methods: and analysis: This is a prospective, randomized, controlled clinical trial with a 2 × 2 factorial design. A total of 120 adult patients undergoing laparoscopic major gastrointestinal surgery will be randomized, in a 1:1:1:1 ratio, to receive one of two patient-controlled analgesia regimens (based on oxycodone or sufentanil) and one of two regional blocks (QLB or TAPB). The primary outcome measure of this trial is the quality of recovery at 24 h after surgery, assessed using the 15-item quality of recovery (QoR-15) scale. The secondary outcomes include QoR-15 scores at 48 and 72 h after surgery; visceral and incisional pain at rest and while coughing at 1, 6, 24 and 48 h postoperatively; analgesic consumption within 0–24 h and 24–48 h postoperatively; need for rescue analgesia; postoperative flatus time; postoperative adverse events (sedation, nausea and vomiting, use of antiemetics, respiratory depression, and dizziness); and length of postoperative hospital stay. Discussion: The results of this trial will provide evidence for the optimal multimodal analgesic strategy to improve the quality of recovery for patients undergoing laparoscopic major gastrointestinal surgery. Trial registration: This trial was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn, identifier: ChiCTR2400080766).

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.

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

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.

Recent research has indicated that the Phyllagathis (raphides) clade (Sonerileae, Melastomataceae) is only distantly related to the type of Phyllagathis and should be separated as a distinct genus. Phylogeny of this clade is here reconstructed with expanded taxon sampling. Four strongly supported subclades have been identified. The possible affinities of taxa that were not sampled in the analysis are discussed, based on morphological data. Perilimnastes is resurrected as the generic name of the Phyllagathis (raphides) clade. A generic description, colour figures, map of distribution, a list of included species and a key are provided for Perilimnastes. Fifteen new combinations are made plus the description of a new species. As interpreted here, Perilimnastes consists of twenty species and two varieties.

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.

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.

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.

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.

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.

Background: Postoperative sleep disturbance (PSD) occurs frequently in patients who undergo major abdominal surgical procedures. Dexmedetomidine is a promising agent to improve the quality of sleep for surgical patients. We designed this trial to investigate the effects of two different doses of intraoperative dexmedetomidine on the occurrence of PSD in elderly patients who have major abdominal surgery. Methods: In this randomized, double-blind, controlled trial, 210 elderly patients aged ≥65 years will be randomized, with an allocation ratio of 1:1:1, to two dexmedetomidine groups (intraoperative infusion of 0.3 or 0.6 μg/kg/h) and a normal saline placebo group. The primary endpoint is the occurrence of PSD on the first night after surgery, assessed using the Athens Insomnia Scale. The secondary endpoints are (1) the incidence of PSD during the 2nd, 3rd, 5th, 7th, and 30th nights postoperatively; (2) pain at rest and on movement at 24 and 48 h postoperatively, assessed using the Numerical Rating Scale; (3) the incidence of postoperative delirium during 0–7 days postoperatively or until hospital discharge, assessed using the 3-min Confusion Assessment Method; (4) depressive symptoms during 0–7 days postoperatively or until hospital discharge, assessed using the 15-items Geriatric Depression Scale; and (5) quality of recovery on postoperative days 1, 2, and 3, assessed using the 15-items Quality of Recovery Scale. Patients' sleep data will also be collected by Xiaomi Mi Band 7 for further analysis. Discussion: The findings of this trial will provide clinical evidence for improving the quality of sleep among elderly patients undergoing major abdominal surgery. Ethics and dissemination: This trial was approved by the Ethics Committee of the First Affiliated Hospital of Soochow University (No. 2023-160). The results will be published in a peer-reviewed journal. Trial registration: Chinese Clinical Trial Registry (ChiCTR2300073163).

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.

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.

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.

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.