Search

Abstract Background Chronic inflammation plays a pivotal role in cancer progression, with tumor-associated neutrophils (TANs) actively shaping the pre-metastatic niche. Interleukin-37 (IL-37), a known immunosuppressive cytokine, is implicated in this regulation, although its precise function remains underexplored.Therefore, this study seeks to further elucidate the inhibitory effect of IL-37d on neutrophil recruitment within the pre-metastatic lung microenvironment and its underlying mechanisms, thereby providing a theoretical foundation for clinical interventions in the early stages of cancer progression. Methods This study investigates the impact of IL-37d on tumor growth, metastasis, and survival in a murine model, with a focus on the molecular mechanisms involved. Specifically, we explored IL-37d's ability to inhibit toll-like receptor 3 (TLR3) activation in lung epithelial cells, reduce calcium-binding proteins S100A8/A9 (S100a8/9) expression, and suppress matrix metalloproteinase 9 (MMP9) activity. We also examined IL-37d’s effect on neutrophil migration from the bone marrow to the lungs during early metastasis. Results IL-37d treatment significantly reduced lung metastasis and extended survival in mice. Mechanistically, IL-37d inhibited TLR3 activation, downregulated S100a8/9 expression, and reduced MMP9 activity, thereby impairing the migration of bone marrow-derived neutrophils to the lungs. This led to decreased neutrophil infiltration and a disruption of the pre-metastatic niche formation. Conclusion Our study represents the first investigation into the role of IL-37d in inhibiting tumor metastasis during the early stages by suppressing S100A8/9 and MMP9 expression in lung tissue, thereby reducing neutrophil recruitment and spontaneous migration from the bone marrow.

Abstract Background Mobile phone addiction (MPA) has numerous deleterious effects on college students, including depression, anxiety, cognitive impairments, and sleep disorders. Undergraduate nursing students play a crucial role as a significant reserve workforce in clinical nursing practice, and their compromised mental health status significantly influences the quality of nursing work and nurse-patient relationships in the future. Objectives This study aims to investigate the associations between neuroticism and MPA among undergraduate nursing students, the mediating effect of self-control and the moderating effect of psychological capital. Methods A total of 900 undergraduate nursing students participated in the survey, wherein the Eysenck Personality Questionnaire Short Form Scale China Version-Neuroticism Subscale (EPQ-RSC-N), Self-Control Scale (SCS), Positive Psychological Capital Questionnaire (PPQ), and Mobile Phone Addiction Tendency Scale (MPATS) were employed for assessment. To analyze the available data, various statistical methods were utilized, including common method bias test examination, descriptive statistics, chi-square tests, independent samples t-tests, Pearson’s correlation analyses, as well as the Hayes’ PROCESS Macro models 4 and 14. Results (1) The prevalence of MPA in this study was found to be 34.89%. (2) The MPA was positively correlated with neuroticism (r = 0.287, p

ObjectiveTo evaluate the effects of Enhanced Recovery After Surgery (ERAS) on postoperative rehabilitation, complications, and long-term prognosis in patients undergoing radical laryngectomy using a single-center propensity score matching (PSM) study.MethodsA retrospective cohort study included patients newly diagnosed with laryngeal cancer between January 1, 2019, and January 1, 2021, scheduled for partial laryngectomy. The control group (CG) comprised patients treated with standard interventions in 2019, while the research group (RG) included patients undergoing ERAS in 2020. After exclusions, 233 individuals remained: 94 in the RG and 204 in the CG. Following PSM in a 2:1 ratio, there were 180 in the CG and 90 in the RG. Relevant indices were analyzed.ResultsNo significant differences were found in baseline characteristics (p > 0.05). The RG showed significantly lower hospital stay, nasogastric tube and tracheal cannula duration, early enteral nutrition, hospitalization expenses, and readmission rates compared to the CG (p 0.05). No significant differences were found in 1-year or 2-year overall survival rates, nor in recurrence-free survival rates between the groups (p > 0.05), though the RG showed marginally better survival.ConclusionERAS treatment for postoperative laryngeal cancer patients reduces hospitalization duration, nasogastric tube and tracheal cannula use, costs, readmission rates, and complications, while accelerating recovery and facilitating early discharge. ERAS enhances patient comfort and clinical outcomes, supporting broader clinical adoption.

BackgroundThe sarcopenia index (SI), derived from serum creatinine and cystatin C levels, has emerged as a novel and accessible biomarker for predicting clinical outcomes. However, its sex-specific prognostic utility in heart failure (HF) remains poorly understood. This study aimed to investigate the association between SI and all-cause mortality in HF, with a focus on sex-specific differences.MethodsA retrospective cohort of 753 patients (median age: 69 years; 61% male) diagnosed with HF from a tertiary hospital in China was analyzed. Cox regression models and Kaplan–Meier survival analyses were utilized to evaluate the relationship between SI and all-cause mortality. Stratified analyses based on sex were performed, and the incremental predictive value of SI was assessed by integrating it into traditional risk models.ResultsOver a median follow-up of 537 days, 143 deaths occurred. In adjusted models, a lower SI was significantly associated with an increased risk of all-cause mortality in male patients (hazard ratio: 0.98 per unit increase, 95% confidence interval: 0.97–0.99, p = 0.002). Males in the lowest SI tertile had a 1.66-fold higher mortality risk than those in the highest tertile (p = 0.004). Kaplan–Meier survival analysis further confirmed these findings, demonstrating significantly lower survival probabilities for males in the lowest SI tertile than for those in higher tertiles (Log-rank p = 0.0013). No such association was observed in females. Adding SI to risk models improved prognostic accuracy in males, enhancing the C-statistic from 0.749 to 0.764 and significantly improving net reclassification and discrimination indices (p

Abstract Pulmonary cryptococcosis (PC) is a common opportunistic fungal infection caused by Cryptococcus neoformans or Cryptococcus gattii. PC primarily invades the respiratory system, followed by the central nervous system. Few clinical reports have examined the coexistence of PC and lung cancer. This study reports the case of a 54-year-old immunocompetent PC patient with lung adenocarcinoma. Chest CT revealed multiple nodules in the right lung, with the largest nodule located in the dorsal segment of the right lower lobe. 18 F‑FDG positron emission tomography-computed tomography (PET-CT) revealed elevated glucose metabolism in the dorsal segment of the right lower lobe, which suggested lung cancer. The metabolism level of the nodule in the basal segment of the right lower lobe and the anterior segment of the right upper lobe was not abnormally increased, but the possibility of a malignant tumour could not be excluded. The pulmonary nodules in the dorsal segment and the basal segment of the right lower lobe were simultaneously resected via video-assisted thoracic surgery (VATS), and the final histopathology revealed primary lung adenocarcinoma and pulmonary cryptococcal infection, respectively. After surgery, antifungal treatment was administered for 3 months. Over the 3-year follow-up, contrast-enhanced computed tomography (CT) revealed no recurrence of either disease. This case study highlights the possibility of dualism in the diagnosis of multiple pulmonary nodules on chest CT, such as the coexistence of lung cancer and PC. Surgical resection is recommended for micronodules that are not easy to diagnose via needle biopsy; in addition, early diagnosis and treatment are helpful for ensuring a good prognosis. This paper reports the clinical diagnosis and treatment of one patient with pulmonary cryptococcal infection of the right lung complicated with lung adenocarcinoma, including 3 years of follow-up, providing a reference for clinical practice.

BackgroundDeveloping self-directed learning in undergraduate nursing students affects not only their learning and their lives, but also their future professional development and the quality of their future practice in clinical nursing. Hence, it is paramount to prioritize and cultivate self-directed learning capabilities among undergraduate nursing students, as this not only enhances their academic pursuits but also equips them with essential lifelong learning skills crucial for the dynamic healthcare landscape.ObjectiveTo delve into the intricate relationship between metacognitive abilities and self-directed learning practices among nursing students, while concurrently examining the mediating roles of psychological capital and interpersonal communication in this interconnected framework. This exploration aims to provide insights into how these factors interplay to influence the self-directed learning capabilities of nursing students.MethodsA total of 662 undergraduate nursing students from one university in China were selected as participants in the survey, utilizing stratified random sampling between September 2023 and December 2023. Of these, an impressive 639 students (96.52%) provided valid responses. The Metacognitive Assessment Inventory, Adolescent Sense of Psychological Capital Scale, Supportive Communication Scale, and Self-Directed Learning Ability Scale were employed to comprehensively assess the metacognitive abilities, psychological capital, interpersonal communication skills, and self-directed learning capacities of nursing students. Pearson correlation analysis was subsequently utilized to delve into the related relationships among these variables. To test the mediating effects, the Bootstrap method, specifically Model 6 of the SPSS-Process package devised by Hayes, was applied.ResultsThe findings revealed a robust positive correlation among metacognitive ability, psychological capital, interpersonal communication ability, and self-directed learning ability, with all associations reaching statistical significance at P < 0.01. Notably, the mediating roles of psychological capital and interpersonal communication in the relationship between metacognitive ability and self-directed learning were significant, as evidenced by the analysis (R2 = 0.347, F = 67.278, P < 0.001). Furthermore, the results indicated that metacognitive ability exerts an indirect influence on self-directed learning through a sequential chain of mediation involving psychological capital and interpersonal communication ability.ConclusionsThis finding highlights the intricate interplay between these factors, suggesting that enhancing nursing students' metacognitive abilities may indirectly bolster their self-directed learning by first fortifying their psychological capital and then fostering stronger interpersonal communication skills.

Abstract Background As indispensable reserves for the nursing workforce, undergraduate nursing students must possess self-directed learning abilities to consistently update their professional knowledge and adapt to the evolving demands of professional development. The acquisition of self-directed learning abilities can help undergraduate nursing students augment their theoretical knowledge and refine their clinical practice skills, thus fulfilling the demand from patients for high-quality nursing services. Hence, comprehending and investigating the factors that influence the development of self-directed learning abilities in nursing students is of paramount importance for nursing education and advancement of the nursing profession. Objectives This study investigated the status of and associations between perceived stress, psychological capital, and self-directed learning abilities among undergraduate nursing students. Additionally, it examines the mediating role of psychological capital in the relationship between perceived stress and self-directed learning abilities. Thus, aiming to provide nursing educators with new directions for enhancing self-directed learning abilities. Design A cross-sectional descriptive study. Methods In February and March 2023, 900 undergraduate nursing students from 10 nursing schools completed an online questionnaire. The questionnaire included measures of perceived stress, psychological capital, and self-directed learning ability. Data were analyzed using SPSS 27.0 and the PROCESS macro tool. Results The scores for perceived stress, psychological capital, and self-directed learning ability among undergraduate nursing students were 40.07 ± 5.90, 99.89 ± 16.59, and 87.12 ± 9.20, respectively. Self-directed learning abilities were negatively correlated with perceived stress (r = -0.415, p

Abstract Background and objective EBUS-TBNA has emerged as an important minimally invasive procedure for the diagnosis and staging of lung cancer. Our objective was to evaluate the effect of different specimen preparation from aspirates on the diagnosis of lung cancer. Methods 181 consecutive patients with known or suspected lung cancer accompanied by hilar / mediastinal lymphadenopathy underwent EBUS-TBNA from January 2019 to December 2022. Specimens obtained by EBUS-TBNA were processed by three methods: Traditional smear cytology of aspirates (TSC), liquid-based cytology of aspirates (LBC) and histopathology of core biopsies. Results EBUS-TBNA was performed in 181 patients on 213 lymph nodes, the total positive rate of the combination of three specimen preparation methods was 80.7%. The diagnostic positive rate of histopathology was 72.3%, TSC was 68.1%, and LBC was 65.3%, no significant differences was observed (p = 0.29); however, statistically significant difference was noted between the combination of three preparation methods and any single specimen preparation methods (p = 0.002). The diagnostic sensitivity of histopathology combined with TSC and histopathology combined with LBC were 96.5 and 94.8%, the specificity was 95.0% and 97.5%, the PPV was 98.8% and 99.4%, the NPV was 86.4% and 81.2%, the diagnostic accuracy was 96.2% and 95.3%, respectively; The sensitivity and accuracy of above methods were higher than that of single specimen preparation, but lower than that of combination of three preparation methods. Conclusion When EBUS-TBNA is used for the diagnosis and staging of lung cancer, histopathology combined with TSC can achieve enough diagnostic efficiency and better cost-effectiveness.

A uniformly distributed global ground network is essential for the accurate determination of GNSS orbit and clock parameters. However, achieving an ideal ground network is often difficult. When limited to a sparse or regional network of ground stations, the integration of LEO satellites can substantially enhance the accuracy of GNSS Precise Orbit Determination (POD). In practical processing, discontinuities with complicated gaps can occur in LEO attitude quaternions, particularly when working with a restricted observation network. This hampers the accuracy of determining GNSS/LEO integrated orbits. To address this, an investigation was conducted using data from seven LEO satellites, including those from Sentinel-3, GRACE-FO, and Swarm, to evaluate integrated POD performance under sparse or regional station conditions. Particular focus was placed on addressing attitude discontinuities. Four scenarios were analyzed, encompassing both continuous data availability and one-, two-, and three-hour interruptions after one hour of continuous data availability. The results showed that the proposed quaternion rotation matrix interpolation method is reliable for the integrated POD of GNSSs and LEOs with strict attitude control.

Background: The incidence of mobile phone addiction (MPA) is increasing in undergraduates and may lead to depression, anxiety, and sleep disorders. Undergraduate nursing students are important group for clinical services; therefore poor mental health has an important implications for the quality of future nursing work and the relationship between nurses and patients. Objectives: To explore the connection between organizational caring and MPA in Chinese undergraduate nursing students and to investigate the mechanisms of perceived stress and self-control in this relationship by constructing a chain mediation model. Design: A cross-sectional study. Methods: A total of 900 participants (age range 18–25 years, M = 20.99, SD = 1.58, 94.0 % female) were recruited from 10 universities in China. Data were collected using an online survey between February and March 2023. Organizational caring, subjective stress, self-control ability, and MPA among undergraduate nursing students were assessed. Results: (1) The prevalence of MPA was 34.9 % (314/900). (2) MPA in undergraduate nursing students was negatively correlated with self-control (r = −0.468, p

Abstract The regulation of proteostasis is fundamental for maintenance of muscle mass and function. Activation of the TGF-β pathway drives wasting and premature aging by favoring the proteasomal degradation of structural muscle proteins. Yet, how this critical post-translational mechanism is kept in check to preserve muscle health remains unclear. Here, we reveal the molecular link between the post-transcriptional regulation of m6A-modified mRNA and the modulation of SMAD-dependent TGF-β signaling. We show that the m6A-binding protein YTHDF2 is essential to determining postnatal muscle size. Indeed, muscle-specific genetic deletion of YTHDF2 impairs skeletal muscle growth and abrogates the response to hypertrophic stimuli. We report that YTHDF2 controls the mRNA stability of the ubiquitin ligase ASB2 with consequences on anti-growth gene program activation through SMAD3. Our study identifies a post-transcriptional to post-translational mechanism for the coordination of gene expression in muscle.

Abstract Heart failure with preserved ejection fraction (HFpEF) is a group of clinical syndromes that exhibit a remarkably heterogeneous phenotype, characterized by symptoms and signs of heart failure, left ventricular diastolic dysfunction, elevated levels of natriuretic peptides, and an ejection fraction greater than or equal to 50%. With the aging of the population and the escalating prevalence of hypertension, obesity, and diabetes, the incidence of HFpEF is progressively rising. Drug therapy options for HFpEF are currently limited, and the associated high risk of cardiovascular mortality and heart failure rehospitalization significantly impact patients' quality of life and longevity while imposing a substantial economic burden on society. Recent research indicates that certain device‐based therapies may serve as valuable adjuncts to drug therapy in patients with specific phenotypes of HFpEF, effectively improving symptoms and quality of life while reducing the risk of readmission for heart failure. These include inter‐atrial shunt and greater splanchnic nerve ablation to reduce left ventricular filling pressure, implantable heart failure monitor to guide diuresis, left atrial pacing to correct interatrial dyssynchrony, cardiac contractility modulation to enhance cardiac calcium handling, as well as renal denervation, baroreflex activation therapy, and vagus nerve stimulation to restore the autonomic imbalance. In this review, we provide a comprehensive overview of the mechanisms and clinical evidence pertaining to these devices, with the aim of enhancing therapeutic strategies for HFpEF.

High-precision Low Earth Orbit (LEO) satellite clocks are essential for LEO-augmented Positioning, Navigation, and Timing (PNT) services. Nowadays, high-precision LEO satellite clocks can be determined in real-time using a Kalman filter either onboard or on the ground, as long as the GNSS observations collected onboard LEO satellites can be transmitted to the ground in real-time. While various real-time and high-precision GNSS products are available nowadays in the latter case, their continuity and latencies in engineering reality are not as perfect as expected and will lead to unignorable impacts on the precision of the real-time LEO satellite clocks. In this study, based on real observations of Sentinel-3B, the impacts of different latencies and continuity of the real-time GNSS products on LEO real-time clocks are determined and discussed for two scenarios, namely the “epoch estimation” and “arc estimation” scenarios. The former case refers to the traditional filter-based processing epoch-by-epoch, and the latter case connects LEO satellite clocks from different rounds of filter-based processing under a certain arc length. The two scenarios lead to the “end-loss” and “mid-gap” situations. Latencies of the real-time GNSS products are discussed for the cases of orbit-only latency, clock-only latency, and combined forms, and different handling methods for the missing GNSS satellite clocks are discussed and compared. Results show that the real-time LEO satellite clock precision is very sensitive to the precision of real-time GNSS satellite clocks, and prediction of the latter becomes essential in case of their latencies. For the “end-loss” situation, with a latency of 30 to 120 s for the GNSS real-time clocks, the LEO satellite clock precision is reduced from about 0.2 to 0.28–0.57 ns. Waiting for the GNSS products in case of their short latencies and predicting the LEO satellite clocks instead could be a better option. For “arc-estimation”, when the gap of GNSS real-time products increases from 5 to 60 min, the real-time LEO clock precision decreases from 0.26 to 0.32 ns.

Objectives: Pleural effusion caused by lung fluke is a rare etiology of exudative pleural effusion (EPE), which is often misdiagnosed or delayed. We aim to summarize the diagnosis and treatment course of EPE caused by lung fluke infection and put forward a practical diagnosis approach.Methods: We retrospectively analyzed the diagnosis and treatment of 14 cases of EPE caused by lung fluke infection diagnosed by enzyme-linked immunosorbent assay of serum antibodies or egg detection.Results: All patients (100%) with an absolute count of eosinophils in peripheral blood exceeded 0.5 × 109/l, and 10 patients (71.4%) had a history of special ingestion. Eosinophilic PE occurred in 11 patients (78.6%), pleural biopsy of medical thoracoscopic demonstrated eosinophils infiltration in nine patients (64.3%), and parasite eggs in one patient. All patients showed positive intradermal tests for Paragonimus-specific antigens and enzyme-linked immunosorbent assay of serum antibodies to Paragonimus.Conclusion: For patients with unexplained PE, lung fluke infection should be highly suspected when pleural fluid or pleural biopsy shows eosinophilic PE or eosinophils infiltration, especially for patients with certain diet history.

BackgroundCavernous haemangiomas (CHs) commonly occurred in the skin, subcutaneous tissue, muscles, and liver. Pulmonary cavernous haemangiomas (PCHs) are quite rare and usually present with nonspecific clinical symptoms. When lung cancer patients are complicated with pulmonary cavernous haemangiomas, radiologically, these haemangioma lesions can be easily misinterpreted as intrapulmonary metastases, potentially resulting in misdiagnosis, or missed diagnosis.Case presentationThe present study reported the case of a 53−year−old female patient with pulmonary adenocarcinoma coexisting with multiple PCHs. 18F−FDG-Positron emission tomography-computed tomography (PET-CT) showed an elevated glucose metabolism in the apicoposterior segment of the left upper lobe; however, the other nodules were not hypermetabolic. Percutaneous lung biopsy was performed on the nodule in the apicoposterior segment of the left upper lobe, which were diagnosed as primary adenocarcinoma. Some nodules in the upper left lobe underwent wedge resection by video-assisted thoracic surgery (VATS) and intraoperative frozen section identified as PCHs. Finally, the patient underwent lobectomy of the left upper lobe via VATS, cancerous nodule in the apicoposterior segment of the left upper lobe underwent genetic molecular testing of PCR−Sanger sequencing, suggested EGFR mutation, and patient received treatment with Osimertinib. During the 4−months follow−up, contrast−enhanced CT showed no recurrence of either disease. PCHs are rare benign tumours of the lung, which can lead to misdiagnosis due to their non-specific clinical symptoms and radiological features, especially when they coexist with lung cancer. PCHs is easily misunderstood as metastatic lung cancer, in this case, PET-CT can assist in differentiating benign from malignant. For the cases of early lung cancer complicated with PCHs, lung cancer can be surgically resected, and whether PCHs should be removed or not should be determined according to the size and distribution of the lesions.

Abstract Introduction Talaromyces marneffei (T. marneffei), a dimorphic fungus, causes local or disseminated infection in humans. We aimed to analyze the clinical characteristics, prognostic factors, and survival outcomes of patients with T. marneffei infection and compare the differences between human immunodeficiency virus (HIV)-positive and HIV-negative subgroups. Methods We retrospectively analyzed 241 patients with T. marneffei infection at the First Affiliated Hospital of Guangxi Medical University between January 2012 and January 2022. The overall population was stratified into HIV-positive (n = 98) and HIV-negative (n = 143) groups according to HIV status. Kaplan–Meier analysis and multivariate Cox regression models were used to determine the prognostic factors for overall survival (OS) and progression-free survival (PFS). Results With a median follow-up time of 58.9 months, 120 patients (49.8%) experienced disease progression and 85 patients (70.8%) died. The 5-year rates of OS and PFS were 61.4% (95% CI 55.0–68.6%) and 47.8% (95% CI 41.5–55.1%), respectively. As an independent factor, patients who were HIV positive had better PFS (HR 0.50, 95% CI 0.31–0.82; p

Objective: To compare the influence of emphysema and lung small shadow on the lung function of patients with pneumoconiosis. Methods: We selected 96 patients who were admitted to the Taihe Hospital (Shiyan city) for pneumoconiosis complicated by emphysema between 2015 and 2020. Chest computed tomography (CT) and lung function assessments were performed. The low attenuation volumes (LAV%) of the whole lung; left and right lungs; and upper, middle, and lower lobes of each lung were quantified using 64-slice spiral CT (GE Optima CT680). Based on the LAV% of the whole lung, the patients were divided into groups A (LAV%30%). The small shadow density (SSD) of the whole lung; left and right lungs; and upper, middle, and lower lung fields was calculated by applying the criteria for evaluating SSD on chest radiographs to CT images. The correlation between SSD and lung function was also analyzed. Results: The SSD of the whole lung was negatively correlated with the forced expiratory volume in the first second (FEV1), total lung capacity (TLC), peak expiratory flow (PEF), maximum expiratory flow after 75% of the forced vital capacity (FVC) has not been exhaled (MEF75%), and maximum expiratory flow after 25% of the FVC has not been exhaled (MEF25%), and it was positively correlated with residual volume (RV)/TLC. LAV% was negatively correlated with FEV1, ratio of FEV to FEV1 (FEV1%), carbon monoxide diffusion capacity (DLCO), PEF, MEF75%, maximum expiratory flow after 50％ of the FVC has not been exhaled (MEF50%), and MEF25% in the whole lung; left and right lungs; and upper, middle, and lower lung lobes; however, it was positively correlated with RV and RV/TLC%. When LAV% was >30%, the correlation between LAV% and FEV1, FEV1%, DLCO, RV/TLC, PEF, MEF75%, MEF50%, and MEF25% was stronger in group C than in groups A and B. A certain degree of correlation was observed between the SSD in the lungs and the ventilation function and volume parameters; however, the correlation between SSD and the diffusion function was weak. Conclusion: The degree of emphysema and SSD in patients with pneumoconiosis have a certain degree of correlation with the lung function; however, the SSD of emphysema has a relatively better correlation with the lung function. It can be used to evaluate the degree of lung injury in patients with pneumoconiosis to a certain extent and is worthy of clinical application.

Abstract Disrupting intracellular redox homeostasis combined with immune checkpoint blockade therapy is considered as an effective way to accelerate tumor cell death. However, suppressed tumor immune microenvironment and lower cargo delivery restrict the efficiency of tumor therapy. In this study, a multifunctional tumor microenvironment (TME)‐responsive nanocomposite is constructed using manganese tetroxide (Mn3O4)‐decorated disulfide‐bond‐incorporated dendritic mesoporous organosilica nanoparticles (DMONs) to co‐deliver indoleamine 2,3‐dioxygenase (IDO) inhibitor Epacadostat (IDOi) and glucose oxidase (GOx) following modification with polyethylene glycol. Owing to the responsiveness of Mn3O4‐decorated DMONs to the mildly acidic and glutathione (GSH) overexpressed TME, the nanocomposite can rapidly decompose and release inner contents, thus substantially improving the cargo release ability. Mn3O4 can effectively catalyze hydrogen peroxide (H2O2) decomposition to generate oxygen, enhance the ability of GOx to consume glucose to produce H2O2, and further promote the generation of hydroxyl radicals (•OH) by Mn2+. Furthermore, Mn2+‐mediated GSH depletion and the production of •OH can disrupt intracellular redox homeostasis, contributing to immunogenic cell death. Simultaneously, IDOi can inhibit IDO to reverse inhibited immune response. The results show that self‐amplifying chemodynamic/starvation therapy combined IDO‐blockade immunotherapy synergistically inhibits tumor growth and metastasis in vivo.

IntroductionThe emergence of cross-modal perception and deep learning technologies has had a profound impact on modern robotics. This study focuses on the application of these technologies in the field of robot control, specifically in the context of volleyball tasks. The primary objective is to achieve precise control of robots in volleyball tasks by effectively integrating information from different sensors using a cross-modal self-attention mechanism.MethodsOur approach involves the utilization of a cross-modal self-attention mechanism to integrate information from various sensors, providing robots with a more comprehensive scene perception in volleyball scenarios. To enhance the diversity and practicality of robot training, we employ Generative Adversarial Networks (GANs) to synthesize realistic volleyball scenarios. Furthermore, we leverage transfer learning to incorporate knowledge from other sports datasets, enriching the process of skill acquisition for robots.ResultsTo validate the feasibility of our approach, we conducted experiments where we simulated robot volleyball scenarios using multiple volleyball-related datasets. We measured various quantitative metrics, including accuracy, recall, precision, and F1 score. The experimental results indicate a significant enhancement in the performance of our approach in robot volleyball tasks.DiscussionThe outcomes of this study offer valuable insights into the application of multi-modal perception and deep learning in the field of sports robotics. By effectively integrating information from different sensors and incorporating synthetic data through GANs and transfer learning, our approach demonstrates improved robot performance in volleyball tasks. These findings not only advance the field of robotics but also open up new possibilities for human-robot collaboration in sports and athletic performance improvement. This research paves the way for further exploration of advanced technologies in sports robotics, benefiting both the scientific community and athletes seeking performance enhancement through robotic assistance.

The fungal cell wall serves as the primary interface between fungi and their external environment, providing protection and facilitating interactions with the surroundings. Chitin is a vital structural element in fungal cell wall. Chitin deacetylase (CDA) can transform chitin into chitosan through deacetylation, providing various biological functions across fungal species. Although this modification is widespread in fungi, the biological functions of CDA enzymes in Aspergillus flavus remain largely unexplored. In this study, we aimed to investigate the biofunctions of the CDA family in A. flavus. The A. flavus genome contains six annotated putative chitin deacetylases. We constructed knockout strains targeting each member of the CDA family, including Δcda1, Δcda2, Δcda3, Δcda4, Δcda5, and Δcda6. Functional analyses revealed that the deletion of CDA family members neither significantly affects the chitin content nor exhibits the expected chitin deacetylation function in A. flavus. However, the Δcda6 strain displayed distinct phenotypic characteristics compared to the wild-type (WT), including an increased conidia count, decreased mycelium production, heightened aflatoxin production, and impaired seed colonization. Subcellular localization experiments indicated the cellular localization of CDA6 protein within the cell wall of A. flavus filaments. Moreover, our findings highlight the significance of the CBD1 and CBD2 structural domains in mediating the functional role of the CDA6 protein. Overall, we analyzed the gene functions of CDA family in A. flavus, which contribute to a deeper understanding of the mechanisms underlying aflatoxin contamination and lay the groundwork for potential biocontrol strategies targeting A. flavus.

The utilization of Low Earth Orbit (LEO) satellites is anticipated to augment various aspects of traditional GNSS-based Positioning, Navigation, and Timing (PNT) services. While the LEO satellite orbital products can nowadays be produced with rather high accuracy in real-time of a few centimeters, the precision of the LEO satellite clock products that can be achieved in real-time is less studied. The latter, however, plays an essential role in the LEO-augmented positioning and timing performances. In real-time, the users eventually use the predicted LEO satellite clocks, with their precision determined by both the near-real-time clock precision and the prediction time needed to match the time window for real-time applications, i.e., the precision loss during the prediction phase. In this study, a real-time LEO satellite clock determination method, consisting of near-real-time clock determination with ultra-short-term clock prediction is proposed and implemented. The principles and strategies of this method are discussed in detail. The proposed method utilized Kalman-filter-based processing, but supports restarts at pre-defined times, thus hampering continuous bias propagation and accumulation from ancient epochs. Based on the method, using Sentinel-3B GNSS observations and the real-time GNSS products from the National Center for Space Studies (CNES) in France, the near-real-time LEO satellite clocks can reach a precision of 0.2 to 0.3 ns, and the precision loss during the prediction phase is within 0.07 ns for a prediction time window from 30 to 90 s. This results in a total error budget in the real-time LEO satellite clocks of about 0.3 ns.

Objective The study objective was to examine alterations in gastrointestinal (GI) microbial composition in patients with systemic sclerosis (SSc) and to investigate the relationship between SSc features and GI microbiota using two independent, international cohorts. Methods Prospective patients with SSc from Lund University (LU), Sweden, from the University of California, Los Angeles (UCLA), United States, and control subjects provided stool specimens for 16S ribosomal RNA sequencing. Alpha and beta diversity analyses were performed. Multivariate negative binomial models identified differentially abundant genera between groups. Results Patients from LU with SSc (n = 106) with recent SSc diagnosis (median disease duration 2.0 years) had lower abundance of commensal genera (eg, Faecalibacterium) and higher abundance of pathobiont genera (eg, Desulfovibrio) than LU‐controls (n = 85). Patients from UCLA with SSc (n = 71) had a similar prevalence of females, a similar body mass index, and similar age but an increased disease duration (median 7.1 years) compared with patients from LU with SSc. Factors associated with beta diversity in patients with SSc from both LU and UCLA included disease duration (P = 0.0016), interstitial lung disease (P = 0.003), small intestinal bacterial overgrowth (P = 0.002), and immunosuppression use (P = 0.014). In multivariable analysis, the UCLA‐SSc cohort had higher abundance of specific pathobiont genera (eg, Streptococcus) compared with the LU‐SSc cohort. Conclusion Enrichments and depletions in certain microbial genera were observed in patients recently diagnosed with SSc, suggesting that dysbiosis is present in early SSc. Specific disease features were independently associated with fecal microbial composition in both cohorts. After controlling for these factors, the abundance of several pathobiont bacteria differed between the cohorts, suggesting that environmental factors, along with disease manifestations, should be considered in future SSc studies.

Background and objectiveMedical thoracoscopy (MT) plays an important role in the diagnosis and treatment of pleural diseases, and rapid on-site evaluation (ROSE) has long been used for transbronchial needle aspiration or fine-needle aspiration to evaluate the adequacy of biopsy materials for the diagnosis of peripheral lung lesions. However, research on ROSE combined with MT for the management of pleural disease has been rarely reported. We aimed to evaluate the diagnostic performance of ROSE for pleura biopsies and visual diagnosis by thoracoscopists for gross thoracoscopic appearance. The secondary objective was to assess the intermodality agreement between ROSE and the final histopathologic diagnosis.MethodsA total of 579 patients with exudative pleural effusion (EPE) who underwent MT combined with ROSE from February 2017 to December 2020 at Taihe Hospital were included in the study. Thoracoscopists' visual diagnosis of gross thoracoscopic appearance, ROSE results, histopathologic findings, and the final diagnosis was recorded.ResultsThoracoscopic pleural biopsies were performed in 565 patients (97.6%); 183 patients were confirmed to have malignant pleural effusion (MPE), and 382 patients were confirmed to have benign pleural effusion (BPE). The area under the curve of ROSE for the diagnosis of MPE was 0.96 (95% CI: 0.94–0.98, p < 0.001), with a sensitivity of 98.7%, a specificity of 97.2%, a diagnostic accuracy of 97.1%, a positive predictive value of 97.2%, and a negative predictive value of 97.2%. Diagnostic consistency between ROSE and histopathology was good (κ ± SE = 0.93 ± 0.02, p < 0.001). The area under the curve of the thoracoscopists' visual diagnosis of gross thoracoscopic appearance was 0.79 (95% CI: 0.75–0.83, p < 0.01), with a sensitivity of 76.7%, a specificity of 80.9%, a positive predictive value of 62.4%, and a negative predictive value of 89.3%.ConclusionROSE of touch imprints of MT biopsy tissue during MT showed high accuracy for distinguishing between benign and malignant lesions. In addition, ROSE was in good agreement with the histopathological diagnosis, which may help thoracoscopists perform pleurodesis (talc poudrage) directly during the procedure, especially in patients with malignant results.

BackgroundSubstantial sex differences exist in atherosclerosis. Excessive reactive oxygen species (ROS) formation could lead to endothelial dysfunction which is critical to atherosclerosis development and progression. Helicobacter pylori (H. pylori) infection has been shown to attenuate endothelial function via exosomes-mediated ROS formation. We have demonstrated that H. pylori infection selectively increases atherosclerosis risk in males with unknown mechanism(s). The present study was to test the hypothesis that H. pylori infection impaired endothelial function selectively in male mice through exosome-mediated ROS formation.Methods and resultsAge-matched male and female C57BL/6 mice were infected with CagA+ H. pylori to investigate sex differences in H. pylori infection-induced endothelial dysfunction. H. pylori infection attenuated acetylcholine (ACh)-induced endothelium-dependent aortic relaxation without changing nitroglycerine-induced endothelium-independent relaxation in male but not female mice, associated with increased ROS formation in aorta compared with controls, which could be reversed by N-acetylcysteine treatment. Treatment of cultured mouse brain microvascular endothelial cells with exosomes from H. pylori infected male, not female, mice significantly increased intracellular ROS production and impaired endothelial function with decreased migration, tube formation, and proliferation, which could be prevented with N-acetylcysteine treatment.ConclusionsH. pylori infection selectively impairs endothelial function in male mice due to exosome-mediated ROS formation.

Wikstroemia nutans Champ. ex Benth., a traditional herbal medicine collected at the Lingnan region of China, was chemically investigated. A new biscoumarin glucoside, wikstronutin (1), along with three known bis- and tricoumarin glucosides (2–4), two flavonoid glycosides (5–6), and eleven lignan glucosides (7–17) were isolated from the stems and roots of W. nutans. The new structure including its absolute configuration was elucidated based on a combination of 1D and 2D NMR, UV, IR, HRESIMS spectroscopic data, as well as chemical transformation. Compounds 1–17 were first isolated from the plant species W. nutans, while compounds 1–3, 8, and 11 were reported from the genus Wikstroemia for the first time. All co-isolates were evaluated for their in vitro inhibitory effects on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in murine RAW264.7 macrophage cells. The antibacterial activity of the selected compounds was also tested. Our work enriches the structure diversity of the secondary metabolites from the genus Wikstroemia.

BackgroundExposure to fine particulate matter (PM) is a significant risk for cardiovascular diseases largely due to increased reactive oxygen species (ROS) production and inflammation. Caspase recruitment domain (CARD)9 is critically involved in innate immunity and inflammation. The present study was designed to test the hypothesis that CARD9 signaling is critically involved in PM exposure-induced oxidative stress and impaired recovery of limb ischemia.Methods and resultsCritical limb ischemia (CLI) was created in male wildtype C57BL/6 and age matched CARD9 deficient mice with or without PM (average diameter 2.8 μm) exposure. Mice received intranasal PM exposure for 1 month prior to creation of CLI and continued for the duration of the experiment. Blood flow and mechanical function were evaluated in vivo at baseline and days 3, 7, 14, and 21 post CLI. PM exposure significantly increased ROS production, macrophage infiltration, and CARD9 protein expression in ischemic limbs of C57BL/6 mice in association with decreased recovery of blood flow and mechanical function. CARD9 deficiency effectively prevented PM exposure-induced ROS production and macrophage infiltration and preserved the recovery of ischemic limb with increased capillary density. CARD9 deficiency also significantly attenuated PM exposure-induced increase of circulating CD11b+/F4/80+ macrophages.ConclusionThe data indicate that CARD9 signaling plays an important role in PM exposure-induced ROS production and impaired limb recovery following ischemia in mice.

The BeiDou-3 system (BDS-3) broadcasts PPP-B2b signals to provide real-time PPP service. Compared with the traditional PPP technique, the PPP-B2b service broadcasts corrections through satellite links, covers a wide area, and is independent of the internet. With the PPP-B2b service, users can obtain high-precision positioning information through the real-time PPP. Many studies have been conducted to evaluate the positioning performance of PPP-B2b. In theory, high-precision timing information could also be obtained through PPP-B2b. With the development of science and technology, the need for highly accurate time measurement, even at the sub-nanosecond level, is experiencing significant growth. However, the GNSS standard timing service can hardly meet these requirements. This contribution analyzes the timing performance of the PPP-B2b service and proposes a sub-nanosecond precise timing method of Coordinated Universal Time (UTC) based on the PPP-B2b service. BDS-3 and GPS observations from nine tracking stations and real-time collected PPP-B2b corrections over 516 days were used to analyze the performance of the proposed timing method. The results show that: (1) The difference between the PPP-B2b-restored UTC, which was realized by one-way timing with the UTC offsets in broadcast ephemeris, and UTC (NTSC), fluctuates within a few ns. (2) The timing uncertainty of the zero baseline based on the proposed method is better than 0.2 ns. (3) Compared with the post-processed PPP time transfer, the UTC dissemination uncertainty of the short and long baseline with the proposed method is better than 0.7 ns. The experiment results verified the feasibility of the proposed sub-nanosecond level precise UTC dissemination method based on the PPP-B2b service.

Abstract There are many clinical scoring criteria for predicting the risk of death in patients with acute ST-segment elevation myocardial infarction (STEMI), but most of the indicators are complex to calculate and are not suitable for use in primary hospitals. Neutrophil to lymphocyte ratio (NLR) and red cell distribution width (RDW) are blood routine indicators that are easy to obtain and may help primary hospitals to evaluate the risk of death in patients with STEMI. Our aim was to explore the predictive value of NLR combined with RDW in the long-term prognosis of patients with STEMI after emergency percutaneous coronary intervention (PCI). A total of 181 patients with STEMI who underwent emergency PCI in the Affiliated Hospital of Pu-tian University from January 2017 to August 2018 were selected. Clinical profile, prognosis of all patients were collected. P value

Abstract Aspergillus flavus is a common saprophytic filamentous fungus that produces the highly toxic natural compound aflatoxin during its growth process. Synthesis of the aflatoxins, which can contaminate food crops causing huge losses to the agricultural economy, is often regulated by epigenetic modification, such as the histone acetyltransferase. In this study, we used Aspergillus flavus as an experimental model to construct the acetyltransferase gene rtt109 knockout strain (△rtt109) and its complementary strain (△rtt109·com) by homologous recombination. The growth of △rtt109 was significantly suppressed compared to the wild type (WT) strain and the △rtt109·com strain. The sclerotium of △rtt109 grew smaller, and the amount of sclerotia generated by △rtt109 was significantly reduced. The number of conidiums of △rtt109 was significantly reduced, especially on the yeast extract sucrose (YES) solid medium. The amount of aflatoxins synthesized by △rtt109 in the PDB liquid medium was significantly decreased We also found that the △rtt109 strain was extremely sensitive to DNA damage stress. Through the maize seed infection experiment, we found that the growth of △rtt109 on the surface of affected corn was largely reduced, and the amount of aerial mycelium decreased significantly, which was consistent with the results on the artificial medium. We further found that H3K9 was the acetylated target of Rtt109 in A. flavus. In conclusion, Rtt109 participated in the growth, conidium formation, sclerotia generation, aflatoxin synthesis, environmental stress response, regulation of infection of A. flavus. The results from this study of rtt109 showed data for acetylation in the regulation of life processes and provided a new thought regarding the prevention and control of A. flavus hazards.

Current studies have found that butyrylcholinesterase (BuChE) replaces the biological function of acetylcholinesterase (AChE) in the late stage of Alzheimer’s disease. Species in the genus of Fallopia, rich in polyphenols with diverse chemical structures and significant biological activities, are considered as an important resource for screening natural products to against AD. In this study, thirty-four compounds (1–34) were isolated from Fallopia dentatoalata (Fr. Schm.) Holub, and their inhibitory effects against AChE and BuChE were assessed. Compounds of the phenylpropanoid sucrose ester class emerged as the most promising members of the group, with 31–33 displaying moderate AChE inhibition (IC50 values ranging from 30.6 ± 4.7 to 56.0 ± 2.4 µM) and 30–34 showing potential inhibitory effects against BuChE (IC50 values ranging from 2.7 ± 1.7 to 17.1 ± 3.4 µM). Tacrine was used as a positive control (IC50: 126.7 ± 1.1 in AChE and 5.5 ± 1.7 nM in BuChE). Kinetic analysis highlighted compounds 31 and 32 as non-competitive inhibitors of AChE with Ki values of ∼30.0 and ∼34.4 µM, whilst 30–34 were revealed to competitively inhibit BuChE with Ki values ranging from ∼1.8 to ∼17.5 µM. Molecular binding studies demonstrated that 30–34 bound to the catalytic sites of BuChE with negative binding energies. The strong agreement between both in vitro and in silico studies highlights the phenylpropanoid sucrose esters 30–34 as promising candidates for use in future anti-cholinesterase therapeutics against Alzheimer’s disease.

Abstract Streptococcus agalactiae (S. agalactiae) is an important pathogen that can lead to neonatus and mother infection. The current existing techniques for the identification of S. agalactiae are limited by accuracy, speed and high-cost. Therefore, a new multiple cross displacement amplification (MCDA) assay was developed for test of the target pathogen immediately from vaginal and rectal swabs. MCDA primers screening were conducted targeting S. agalactiae pcsB gene, and one set of MCDA primers with better rapidity and efficiency was selected for establishing the S. agalactiae-MCDA assay. As a result, the MCDA method could be completed at a constant temperature of 61 °C, without the requirement of special equipment. The detection limit is 250 fg (31.5 copies) per reaction, all S. agalactiae strains displayed positive results, but not for non-S. agalactiae strains. The visual MCDA assay detected 16 positive samples from 200 clinical specimen, which were also detected positive by enrichment/qPCR. While the CHROMagar culture detected 6 positive samples. Thus, the MCDA assay is prefer to enrichment/qPCR and culture for detecting S. agalactiae from clinical specimen. Particularly, the whole test of MCDA takes about 63.1 min, including sample collection (3 min), DNA preparation (15 min), MCDA reaction (45 min) and result reporting (6 s). In addition, the cost was very economic, with only US$ 4.9. These results indicated that our S. agalaciae-MCDA assay is a rapid, sensitive and cost-efficient technique for target pathogen detection, and is more suitable than conventional assays for an urgent detection, especially for 'on-site' laboratories and resource-constrained settings.

Background Left atrial enlargement (LAE) is a common cardiac structural change in patients with hypertension, and obesity could further promote LAE. However, little is known about the effect of overweight on left atrial size, and if there is a gender difference of the effect. The aim of this study was to analyze the effects of different body mass index (BMI) grades (normal weight, overweight, and obesity) on left atrial size in both male and female patients with hypertension. Methods A total of 710 patients with hypertension were divided into 3 study groups: normal weight group (BMI < 24 g/m2, n = 302), overweight group (24 kg/m2 ≤ BMI < 28 kg2, n = 318), and obesity group (BMI ≥28 kg/m2, n = 90). The clinical data, echocardiographic indexes and left atrial size were obtained from all the subjects. Pearson correlation analysis was used to analyze the correlation between clinical variables and left atrial diameter (LAD)/left atrial diameter index (LADI), and stepwise regression evaluation was used to study the relevant factors affecting LAD/LADI among all patients, male and female patients for possible gender difference. Results The significant difference in LADI was noted in the three study groups with obesity group of 23.96 ± 2.90 mm/m, overweight group of 22.50 ± 3.02 mm/m and normal weight group of 21.08 ± 2.80 mm/m, respectively (P .05). For each additional unit of BMI, LAD increased by 0.034 mm and LADI increased by 0.305 mm/m. Multiple linear regression analysis showed that BMI, left ventricular mass index (LVMI), age and female gender were independently correlated with LADI (P

Bretschneidera sinensis is an endangered woody species found in East and South China. Comprehensive intraspecies chloroplast genome studies have demonstrated novel genetic resources to assess the genetic variation and diversity of this species. Using genome skimming method, we assembled the whole chloroplast genome of 12 genotypes of B. sinensis from different geographical locations, covering most wild populations. The B. sinensis chloroplast genome size ranged from 158,959 to 159,045 base pairs (bp) and displayed a typical circular quadripartite structure. Comparative analyses of 12 B. sinensis chloroplast genome revealed 33 polymorphic simple sequence repeats (SSRs), 105 polymorphic single nucleotide polymorphisms (SNPs), and 55 indels. Phylogenetic analysis showed that the 12 genotypes were grouped into 2 branches, which is consistent with the geographical distribution (Eastern clade and Western clade). Divergence time estimates showed that the two clades were divergent from 0.6 Ma in the late Pleistocene. Ex situ conservation is essential for this species. In this study, we identified SNPs, indels, and microsatellites of B. sinensis by comparative analyses of chloroplast genomes and determined genetic variation between populations using these genomic markers. Chloroplast genomic resources are also important for further domestication, population genetic, and phylogenetic analysis, possibly in combination with molecular markers of mitochondrial and/or nuclear genomes.

Background and ObjectiveInflammatory bowel disease (IBD) produces significant local and systemic inflammation with increased reactive oxygen species (ROS) formation. IBD Patients are at an increased risk for developing endothelial dysfunction and cardiovascular diseases. The present study tested the hypothesis that IBD impairs aortic endothelial function via ROS formation and investigate potential sex-related differences.Methods and ResultsAcute and chronic colitis models were induced in male and female C57BL/6 mice with dextran sodium sulfate (DSS) treatment. Aortic wall stiffness, endothelial function, and ROS levels, as well as serum levels of pro-inflammatory cytokines were evaluated. Acetylcholine (Ach)-induced endothelium-dependent relaxation of abdominal aorta without perivascular adipose tissue (PVAT) was significantly reduced in female mice, not males, with chronic colitis without a change in nitroglycerin-induced endothelium-independent relaxation. PVAT effectively preserved Ach-induced relaxation in abdominal aorta of female mice with chronic colitis. Aortic peak velocity, maximal intraluminal diameters, pulse wave velocity, distensibility and radial strain were preserved in mice with both acute and chronic colitis. Although pro-inflammatory cytokines levels were increased in mice with acute and chronic colitis, aortic ROS levels were not increased.ConclusionThe data demonstrate that abdominal aortic endothelial function was attenuated selectively in female mice with chronic colitis independent of ROS formation. Further, PVAT played an important role in preserving endothelial function in female mice with chronic colitis.

AimBone marrow biopsy is essential and necessary for the diagnosis of patients with aplastic anemia (AA), myelodysplastic syndromes (MDS), and acute myeloid leukemia (AML). However, the convolutional neural networks (CNN) model that automatically distinguished AA, MDS, and AML based on bone marrow smears has not been reported.MethodsImage-net pretrained model of CNN was used to construct the recognition model. Data extracted from the American Society of Hematology (ASH) Image Bank were utilized to develop the model and data extracted from the clinic were used for external validation. The model had two output layers: whether the patient was MDS (two-classification) and which of AA, MDS, and AML the patient was (three-classification). Different outcome weights (two-classification/three-classification = 5:5, 2:8, 1:9) and epochs (30, 50, 200) were used to select the optimal model. The model performance was evaluated by the Accuracy-Loss curves and calculating the area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).ResultsA total of 115 bone marrow smears from the ASH Image Bank and 432 bone marrow smears from the clinic were included in this study. The results of Accuracy-Loss curves showed that the best model training effect was observed in the model with the outcome weight and epoch of 1:9 and 200. Similarly, this model also performed well performances in the two-classification of MDS and the three-classification of AA, MDS, AML. The AUC, accuracy and sensitivity of the MDS two-classification model in the testing set were 0.985 [95% confidence interval (CI), 0.979-0.991], 0.914 (95%CI, 0.895-0.934), and 0.992 (95%CI, 0.980-1.000), respectively. The AUC, accuracy and sensitivity of the AA, MDS, AML three-classification model in the testing set were 0.968 (95%CI, 0.960-0.976), 0.929 (95%CI, 0.916-0.941), and 0.857 (95%CI, 0.828-0.886), respectively.ConclusionThe image-net pretrained model was able to obtain high accuracy AA, MDS, AML distinction, and may provide clinicians with a convenient tool to distinguish AA, MDS, and AML.

Background and Objective: Computed tomography-guided percutaneous lung biopsy is a commonly used method for clarifying the nature of nodules, masses or lung consolidation. However, the diagnostic yield of nodules needs to be improved when compared with masses during percutaneous lung biopsy. In recent years, 3D-printed coplanar templates have been gradually utilized in radioactive seed implantation for lung cancer treatment. However, there is little research on the application of 3D-printed coplanar templates in pulmonary nodules biopsy. Therefore, we conducted a single center and retrospective study to explore the application value of 3D-printed coplanar puncture template-assisted computed tomography-guided percutaneous core needle biopsy of small pulmonary nodules. Methods: 210 patients hospitalized in Taihe Hospital with pulmonary nodules underwent percutaneous core needle biopsy for histopathology diagnosis and were included in the study. 106 patients underwent conventional percutaneous lung biopsy (control group) and 104 patients underwent 3D-PCT-assisted percutaneous lung biopsy (3D-PCT group). The diagnostic yield and incidence of complications were recorded and compared between the two groups. Results: The overall diagnostic yield significantly improved in 3D-PCT group (95.2%) compared with Control group (87.7%) ( P .05). Conclusions: Studies indicated that application of 3-Dimensionally printed coplanar template improves diagnostic yield of CT-guided percutaneous core needle biopsy for pulmonary nodules, especially for pulmonary nodule smaller than 2 cm.

Facile, and low-cost preparation of three-dimensional graphene nanomesh (3D-GNM) with electrocatalytic sites and its application in electrochemical sensors is still a challenge. Herein, we demonstrate a fast and convenient strategy to prepare free-standing 3D-GNM, which possesses in-plane nanopores, artificial function edges and electrocatalytic properties. 3D graphene foam (3D-G) with monolithic and macroporous structure serves as the starting electrode. 3D-GNM is easily prepared by simple electrochemical polarization of 3D-G, including anodic oxidation (anodization, +5 V, in ionic liquid-IL electrolyte) and subsequent cathodic reduction (cathodization, −1 V, in phosphate buffer solution-PBS), which can be completed within 10 min. 3D-GNM exhibits well-separated oxidation peaks towards dopamine (DA), uric acid (UA), and ascorbic acid (AA). Compared with that on 3D-G, the oxidation potentials of DA, UA, and AA on 3D-GNM respectively have cathodic shifts of 180 mV, 130 mV and 290 mV and the current intensities of DA and UA increase by 52 times and 12 times. Selective determination of DA, UA and AA in ternary mixture (limit of detection is 0.26 μM, 6.0 nM and 3.1 μM, respectively) or biological (serum) samples is achieved.

BackgroundHelicobacter pylori (H. pylori) infection increases the risk for atherosclerosis, and ROS are critical to endothelial dysfunction and atherosclerosis. CagA is a major H. pylori virulence factor associated with atherosclerosis. The present study aimed to test the hypothesis that CagA+H. pylori effectively colonizes gastric mucosa, and CagA+H. pylori, but not CagA–H. pylori, infection impairs endothelial function through exosomes-mediated ROS formation.MethodsC57BL/6 were used to determine the colonization ability of CagA+H. pylori and CagA–H. pylori. ROS production, endothelial function of thoracic aorta and atherosclerosis were measured in CagA+H. pylori and CagA–H. pylori infected mice. Exosomes from CagA+H. pylori and CagA–H. pylori or without H. pylori infected mouse serum or GES-1 were isolated and co-cultured with bEND.3 and HUVECs to determine how CagA+H. pylori infection impairs endothelial function. Further, GW4869 was used to determine if CagA+H. pylori infection could lead to endothelial dysfunction and atherosclerosis through an exosomes-mediated mechanism.ResultsCagA+H. pylori colonized gastric mucosa more effectively than CagA–H. pylori in mice. CagA+H. pylori, not CagA–H. pylori, infection significantly increased aortic ROS production, decreased ACh-induced aortic relaxation, and enhanced early atherosclerosis formation, which were prevented with N-acetylcysteine treatment. Treatment with CagA-containing exosomes significantly increased intracellular ROS production in endothelial cells and impaired their function. Inhibition of exosomes secretion with GW4869 effectively prevented excessive aortic ROS production, endothelial dysfunction, and atherosclerosis in mice with CagA+H. pylori infection.ConclusionThese data suggest that CagA+H. pylori effectively colonizes gastric mucosa, impairs endothelial function, and enhances atherosclerosis via exosomes-mediated ROS formation in mice.

Recent studies have confirmed the role of plasma donor-derived cell-free DNA (ddcfDNA) as a reliable non-invasive biomarker for allograft injury after kidney transplantation. Whereas the variability of plasma ddcfDNA levels among recipients has limited their clinical use. This study aimed to explore the intrinsic factors associated with plasma ddcfDNA elevation by investigating the impact of Banff lesions and inflammatory infiltrates on ddcfDNA levels in kidney transplant recipients. From March 2017 to September 2019, a total of 106 kidney transplant recipients with matched allograft biopsies were included, consisting of 13 recipients with normal/nonspecific changes, 13 recipients with borderline changes, 60 with T cell-mediated rejection, and 20 with antibody-mediated rejection. Histologic classification was performed according to the Banff 2017 criteria by two experienced pathologists. Plasma ddcfDNA fractions ranged from 0.12% to 10.22%, with a median level of 0.91%. Banff histology subelements including glomerulitis, intimal arteritis, and severe interstitial inflammation were correlated with increased plasma ddcfDNA levels. The inflammatory cell infiltrate in the allografts was phenotyped by immunochemistry and automatically counted by digital image recognition. Pearson correlation analysis revealed a significant positive correlation between macrophage infiltrations in allografts and plasma ddcfDNA levels. Additionally, macrophage extracellular trap (MET) activity was significantly associated with the rise in plasma ddcfDNA levels. Our findings demonstrated that plasma ddcfDNA could reflect the inflammatory state in renal allografts and suggested the potential role of METs in the pathogenesis of allograft injury.

Antibody-mediated rejection (ABMR) is a major cause of dysfunction and loss of transplanted kidney. The current treatments for ABMR involve nonspecific inhibition and clearance of T/B cells or plasma cells. However, the prognosis of patients following current treatment is poor. T follicular helper cells (Tfh) play an important role in allograft-specific antibodies secreting plasma cell (PC) development. Tfh cells are therefore considered to be important therapeutic targets for the treatment of antibody hypersecretion disorders, such as transplant rejection and autoimmune diseases. Tacrolimus (Tac), the primary immunosuppressant, prevents rejection by reducing T cell activation. However, its administration should be closely monitored to avoid serious side effects. In this study, we investigated whether Tac delivery to helper T (CD4+) cells using functionalized mesoporous nanoparticles can block Tfh cell differentiation after alloantigen exposure. Results showed that Tac delivery ameliorated humoral rejection injury in rodent kidney graft by suppressing Tfh cell development, PC, and donor-specific antibody (DSA) generation without causing severe side effects compared with delivery through the drug administration pathway. This study provides a promising therapeutic strategy for preventing humoral rejection in solid organ transplantation. The specific and controllable drug delivery avoids multiple disorder risks and side effects observed in currently used clinical approaches.

Background: The use of extracorporeal membrane oxygenation (ECMO) to support critically ill patients with cardiorespiratory dysfunction has increased over the last decades. However, hemorrhagic complications occur frequently during ECMO support, and this has a significant impact on morbidity and mortality. Thus, this study aimed to identify the risk factors for hemorrhage in patients receiving ECMO.Methods: Our retrospective study included 60 patients, who were admitted to the Taihe Hospital in Shiyan City, Hubei Province, China from February 2017 to October 2020. About 18 patients developed hemorrhagic complications, and 42 patients did not demonstrate such complications. Data regarding patient demography, laboratory tests, and clinical manifestations prior to ECMO were collected to analyze their clinical features. Univariable and multivariable logistic analyses were used to explore the risk factors for hemorrhage in adults on ECMO. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of the binary logistic model. The amount of blood transfusions was compared between the two groups, and the activated partial thromboplastin time (APTT), platelet count, and hemoglobin level before the initiation of ECMO.Results: Logistic analysis showed that a longer duration of ECMO support, higher APTT, and lower platelet count prior to ECMO were independent risk factors for hemorrhage in adults on ECMO. In addition, we found that the cannula site was the most common bleeding site. Most bleeding events occurred within the first 3 days of ECMO therapy. After the ECMO initiation, APTT was prolonged while the platelet count and hemoglobin levels were decreased. The amount of blood transfusion was significantly higher in the hemorrhage group than in the non-hemorrhage group.Conclusions: Clinicians should evaluate the risk of hemorrhage based on the coagulation function of patients, underlying disease, and the duration of ECMO support. In the first 3 days during ECMO support, special attention should be given to the cannula site, mucosal, and dermal regions, and digestive tract to detect any signs of hemorrhage. Moreover, increasing the platelet count transfusion threshold and accurately determining the amount of blood transfusion required may prevent bleeding events.

Atherosclerotic cardiovascular disease and subsequent heart failure threaten global health and impose a huge economic burden on society. MicroRNA-132 (miR-132), a regulatory RNA ubiquitously expressed in the cardiovascular system, is up-or down-regulated in the plasma under various cardiac conditions and may serve as a potential diagnostic or prognostic biomarker. More importantly, miR-132 in the myocardium has been demonstrated to be a master regulator in many pathological processes of ischemic or nonischemic heart failure in the past decade, such as myocardial hypertrophy, fibrosis, apoptosis, angiogenesis, calcium handling, neuroendocrine activation, and oxidative stress, through downregulating target mRNA expression. Preclinical and clinical phase 1b studies have suggested antisense oligonucleotide targeting miR-132 may be a potential therapeutic approach for ischemic or nonischemic heart failure in the future. This review aims to summarize recent advances in the physiological and pathological functions of miR-132 and its possible diagnostic and therapeutic potential in cardiovascular disease.

Mangrove-derived endophytes are rich in bioactive secondary metabolites with a variety of biological activities. Recently, a fungus Pseudofusicoccum sp. J003 was first isolated by our research group from mangrove species Sonneratia apetala Buch.-Ham. The subsequent chemical investigation of the methanol extract of the culture broth of this strain has led to the isolation of a new sesquiterpenoid named acorenone C (1), two alkaloids (2–3), four phenolic compounds (4–7), and four steroid derivatives (8–11). The new structure of 1 was established by extensive spectroscopic analysis, including 1D, 2D NMR spectroscopy, and HRESIMS. Its absolute configuration was elucidated by experimental ECD and ECD calculation. The in vitro AChE inhibitory, anti-inflammatory, and cytotoxic activities of the selected compounds were evaluated. The results showed that compound 1 showed mild AChE inhibitory activity, with an inhibition rate of 23.34% at the concentration of 50 μM. Compound 9 exerted a significant inhibitory effect against nitric oxide (NO) production in LPS-stimulated RAW 264.7 mouse macrophages, with an inhibition rate of 72.89% at the concentration of 25 μM, better than that of positive control L-NMMA. Compound 9 also displayed obvious inhibition effects on the growth of two human tumor cell lines, HL-60 and SW480 (inhibition rates 98.68 ± 0.97% and 60.40 ± 4.51%, respectively). The antimicrobial activities of the compounds (1–11) against Escherichia coli, Bacillus subtilis, Staphylococcus aureus, and Pseudomonas aeruginosa were also tested; however, none of them showed antimicrobial activities.

Background Therapy with mesenchymal stem cells remains a promising but challenging approach to critical limb ischemia in diabetes because of the dismal cell survival. Methods and Results Critical limb ischemia in type 2 diabetes mouse model was used to explore the impact of diabetic limb ischemia on the survival of bone marrow mesenchymal stromal cells (bMSCs). Inhibition of intracellular reactive oxygen species was achieved with concomitant overexpression of superoxide dismutase (SOD)‐1 and glutathione peroxidase‐1 in the transplanted bMSCs, and extracellular reactive oxygen species was attenuated using SOD‐3 overexpression and N‐acetylcysteine treatment. In vivo optical fluorescence imaging and laser Doppler perfusion imaging were used to track cell retention and determine blood flow in diabetic ischemic limb, respectively. Survival of the transplanted bMSCs was significantly decreased in diabetic ischemic limb compared with the control. In vitro study indicated that advanced glycation end products, not high glucose, significantly decreased the proliferation of bMSCs and increased their apoptosis associated with increased reactive oxygen species production and selective reduction of SOD‐1 and SOD‐3. In vivo study demonstrated that concomitant overexpression of SOD‐1, SOD‐3, and glutathione peroxidase‐1, or host treatment with N‐acetylcysteine, significantly enhanced in vivo survival of transplanted bMSCs, and improved critical limb ischemia in diabetic mice. Combination of triple antioxidant enzyme overexpression in bMSCs with host N‐acetylcysteine treatment further improved bMSC survival with enhanced circulatory and functional recovery from diabetic critical limb ischemia. Conclusions Simultaneous suppression of reactive oxygen species from transplanted bMSCs and host tissue could additively enhance bMSC survival in diabetic ischemic limb with increased therapeutic efficacy in diabetes.

Abstract Background Bronchial Dieulafoy’s disease (BDD) is a rare disease that is known to be a cause of hemorrhage. The characteristics of this disease are still unknown. The present study describes the disorder based on a review of the world’s literature, emphasizing the diagnostic and therapeutic views. Methods A comprehensive research of BDD of the PubMed, Google Scholar, and Web of Science databases was performed. The following data were collected: patient characteristics; chest imaging, bronchoscopy, vascular angiography, and histopathologic examination findings; and treatment rendered. Results 73 cases of BDD have been reported from 1995 to 2019. Most of the cases occurred in Asia (52.1%), followed by Europe (31.5%). Chest imaging findings were non-specific. The main bronchoscopy finding was a nodular or protruding lesion (60.9%). 19 patients underwent bronchoscopic biopsies, 17 had bleeding, and 6 died. Four patients were successfully shown to have vascular malformations under mucosal protrusion by endobronchial ultrasound scan (EBUS). Vascular angiography mainly showed tortuous, dilated bronchial arteries. Vascular angiography mainly showed tortuous, dilated bronchial arteries. The arterial supply was mainly provided by bronchial arteries (48 cases) and the pulmonary circulation (4 cases). The lesions were mainly located in the right bronchus (53 cases). Selective bronchial artery embolization (BAE) was attempted in 38 patients and 20 patients underwent lobectomies. Emergency resection was performed in 15 patients, all of whom survived and had no recurrent hemoptysis. Conclusions Massive hemoptysis was the common manifestation of BDD. Vascular angiography and EBUS is a very useful examination before biopsy. BAE may be used in stable patients, or patients who cannot tolerate surgery, while surgical resection should be considered in patients who are unstable, patients with uncontrolled hemoptysis, or following BAE failure.

Rapid and highly sensitive quantitative analysis of chlorpromazine (CPZ) in human whole blood is of great importance for human health. Herein, we utilize the screen-printed carbon electrodes (SPCE) as the electrode substrates for growth of highly electroactive and antifouling nanocomposite materials consisting of vertically ordered mesoporous silica films (VMSF) and electrochemically reduced graphene oxide (ErGO) nanosheets. The preparation of such VMSF/ErGO/SPCE could be performed by using an electrochemical method in a few seconds and the operation is controllable. Inner ErGO layer converted from graphene oxide (GO) in the growth process of VMSF provides oxygen-containing groups and two-dimensional π-conjugated planar structure for stable fabrication of outer VMSF layer. Owing to the π-π enrichment and excellent electrocatalytic abilities of ErGO, electrostatic preconcentration and antifouling capacities of VMSF, and inherent disposable and miniaturized properties of SPCE, the proposed VMSF/ErGO/SPCE sensor could be applied for quantitative determination of CPZ in human whole blood with high accuracy and sensitivity, good stability, and low sample consumption.

Objectives: To investigate the effect and mechanism of sacubitril/valsartan on myocardial fibrosis in rats following experimental myocardial infarction and in TGF-β1-treated myocardial fibroblasts.Methods: Male Sprague-Dawley (SD) rats were subjected to coronary artery ligation to establish myocardial infarction and intragastrically fed vehicle, valsartan (Val, 32 mg/kg, once-daily) or sacubitril/valsartan (Sac/Val, 68 mg/kg, once-daily) for 4 weeks. In parallel, myocardial fibroblasts (MFs) isolated from neonatal SD rats were exposed to hypoxia and treated with TGF-β1 (5 ng/ml) plus vehicle, Val (107–10–5 M) or Sac/Val (107–105 M). Rat cardiac function and fibrosis were measured by echocardiography and histological method, respectively. MFs viability and collagen synthesis were determined by cell counting kit-8 and enzyme-linked immunosorbent assay, respectively. Protein expressions of TGF-β1, Smad3, phosphorylated Smad3 (p-Smad3), and p-Smad3 subcellular localization were detected by immunoblotting and immunocytochemistry.Results: Sac/Val significantly improved cardiac structure and function in rats after myocardial infarction, including decreased left ventricular end-diastolic diameter and interventricular septal thickness, increased ejection fraction, and reduced myocardial collagen volume fraction and type Ⅰ and type Ⅲ collagen levels, and this effect was superior to that of Val. Besides, Sac/Val inhibited myocardial TGF-β1 and p-Smad3 protein expression better than Val. Mechanically, Sac/Val significantly attenuated TGF-β1-induced proliferation and collagen synthesis of MFs, and inhibit Smad3 phosphorylation and nucleus translocation, and this effect outperformed Val. Overexpression and silencing of Smad3 enhanced and reversed the inhibitory effects of Sac/Val on TGF-β1-induced collagen synthesis by MFs, respectively.Conclusions: Sacubitril/valsartan improves cardiac function and fibrosis in rats after experimental myocardial infarction, and this effect is related to the inhibition of collagen synthesis in myocardial fibroblasts by inhibiting the TGF/Smads signaling pathway.

The microphthalmia-associated transcription factor (MITF) is an important transcription factor that plays a key role in melanogenesis, cell proliferation, survival and immune defense in vertebrate. However, its function and function mechanism in bivalve are still rarely known. In this research, first, a Mitf gene was characterized from Pteria penguin (P. penguin). The PpMitf contained an open reading frame of 1,350 bp, encoding a peptide of 449 deduced amino acids with a highly conserved basic helix-loop-helix-leucine zipper (bHLH-LZ) domain. The PpMITF shared 55.7% identity with amino acid sequence of Crassostrea gigas (C. gigas). Tissue distribution analysis revealed that PpMitf was highly expressed in mantle and hemocytes, which were important tissues for color formation and innate immunity. Second, the functions of PpMitf in melanin synthesis and innate immunity were identified. The PpMitf silencing significantly decreased the tyrosinase activity and melanin content, indicating PpMitf involved in melanin synthesis of P. penguin. Meanwhile, the PpMitf silencing clearly down-regulated the expression of PpBcl2 (B cell lymphoma/leukemia-2 gene) and antibacterial activity of hemolymph supernatant, indicating that PpMitf involved in innate immunity of P. penguin. Third, the function mechanism of PpMitf in immunity was analyzed. The promoter sequence analysis of tyrosinase (Tyr) revealed two highly conserved E-box elements, which were specifically recognized by HLH-LZ of MITF. The luciferase activities analysis showed that Mitf could activate the E-box in Tyr promoter through highly conserved bHLH-LZ domain, and demonstrated that PpMitf involved in melanin synthesis and innate immunity by regulating tyrosinase expression. Finally, melanin from P. penguin, the final production of Mitf-Tyr-melanin pathway, was confirmed to have direct antibacterial activity. The results collectively demonstrated that PpMitf played a key role in innate immunity through activating tyrosinase-mediated melanin synthesis in P. penguin.

Inflammatory bowel disease (IBD) produces significant systemic inflammation and increases the risk of endothelial dysfunction and peripheral artery disease. Our recent study demonstrated that abdominal aortic endothelial cell function was impaired selectively in female mice with chronic colitis. This study aimed to test the hypothesis that experimental colitis leads to femoral artery endothelial cell dysfunction and impairs limb ischemia recovery in female mice. An experimental chronic colitis model was created in female C57BL/6 mice with dextran sodium sulfate (DSS) treatment. Unilateral hind limb ischemia was produced by femoral artery ligation. Limb blood perfusion, vascular density, tissue ROS levels, and plasma levels of proinflammatory cytokines were assessed. Femoral artery endothelium-dependent and -independent vasodilation of the contralateral limb were evaluated ex vivo using acetylcholine and nitroglycerin, respectively. As expected, the plasma levels of proinflammatory cytokines, including tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, and IL-17, were significantly increased in the DSS-induced colitis model. However, ROS levels in the ischemic muscle tissues were not significantly increased in colitis model as compared to the controls. There were no significant changes in endothelium-dependent or -independent vasodilation of the femoral artery between colitis model and the control. Recovery of function and blood flow in the ischemic limb and capillary density in the ischemic gastrocnemius muscle were preserved in the colitis model as compared with the control. The data demonstrated that DSS-induced chronic colitis had no significant impact on femoral artery endothelial function or ischemic limb recovery in female mice.