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Background Bronchopulmonary dysplasia (BPD) is a common chronic lung disease in premature infants and hyperoxia exposure is a major cause. In hyperoxic lung injury animal model, alveolar simplification and pro-inflammatory cells infiltration are the main pathophysiologic changes. Caffeine is a drug used to treat apnea in premature infants. Early use of caffeine can decrease the rate and the severity of BPD while the mechanisms are still unclear. The purpose of this study was to evaluate the effects of caffeine on inflammation and lung development in neonatal mice with hyperoxic lung injury and to explore the possible mechanism. Methods Following 14 d of 75% oxygen exposure in newborn mouse, the BPD model was established. Caffeine at a dose of 1 g/L was added in drinking water to nursing mouse. We measured the concentration of caffeine in serum and oxidative stress in lung by commercially available kits. Adenosine 2A receptor (A 2A R) expression and lung inflammation were measured by Immunohistochemistry and western blotting. Apoptosis and surfactant protein-C (SFTPC) levels were measured by immunofluorescence. The inflammasome and NF-κB pathway proteins were assessed by western blotting. Results We found that the caffeine concentration in plasma at present dose significantly decreased the expression of A 2A R protein in mice lung. Caffeine treatment significantly reduced oxidative stress, improved weight gain, promoted alveolar development, attenuated inflammatory infiltration and lung injury in hyperoxia-induced lung injury mice. Moreover, caffeine decreased the cell apoptosis in lung tissues, especially the Type II alveolar epithelial cell. The expression of NLRP3 inflammasome protein and NF-κB pathway were significantly inhibited by caffeine treatment. Conclusion Caffeine treatment can protect hyperoxia-induced mice lung from oxidative injury by inhibiting NLRP3 inflammasome and NF-κB pathway.

The present study identified the effects of heat oxidation on protein carbonyl content and α,α-diphenyl-β-picrylhydrazyl (DPPH) free radical-scavenging activity in soy protein. The changes on antioxidant status in male mice fed a heat-oxidized diet were also investigated. Soy protein heated at 100°C for 30, 60, and 90 min was used to determine the protein carbonyl content and DPPH free radical-scavenging activity in vitro. Male KM mice (3 wk old) were fed a normal diet, an oxidized diet (HD) containing 12% heat-oxidized soy protein, or an HD supplemented with 0.1% lipoic acid. After 4 wk of feeding, apparent digestibility, reactive oxygen species, malondialdehyde, and total antioxidant capacity levels were measured. The antioxidant enzyme activities in serum and tissues were also assayed. Heat-oxidized soy protein showed a significant increase in protein carbonyl formation and a decrease in DPPH free radical-scavenging activity. The HD induced a significant decrease in food intake and apparent digestibility of dry matter and crude protein in mice. Increased levels of reactive oxygen species and malondialdehyde in serum and tissues accompanied by decreased total antioxidant capacity and antioxidant enzyme activities were also observed in HD-fed mice. These changes were partly restored in the lipoic acid–treated group. Heat-oxidized soy protein showed a relatively higher protein carbonyl content and a loss of its free radical-scavenging activity in vitro. The heat oxidation also led the soy protein to generate reactive oxygen species, decrease the antioxidant status, and induce redox imbalance in vivo. The heat oxidation of food protein could be a potential health risk in humans.

Cancer‐associated fibroblasts (CAFs) are essential players in the tumor microenvironment (TME) due to their roles in facilitating tumor progression and metastasis. It is worth noting that the high‐metastatic hepatocellular carcinoma (HCC) cell‐derived exosomes have exhibited the ability to transform normal fibroblasts into CAFs, which further fosters the lung metastasis of low‐metastatic HCC cells. Yet, the mechanisms underlying this tumor exosome‐induced metastatic niche formation are poorly explored. In this study, the secreted protein arginyl aminopeptidase (RNPEP) was highly expressed in the plasma of patients with HCC. In addition, high‐metastatic HCC cells showed augmented RNPEP expression levels in their exosomes. These exosomes induced obvious CAF‐like properties in the human fibroblast cell line MRC‐5, as evidenced by the increased CAF marker expression, and enhanced migratory ability. More strikingly, the secretions from high‐metastatic tumor exosome‐educated MRC‐5 cells increased tumor stemness and promoted epithelial–mesenchymal transition (EMT) in MHCC‐97L cells, a low‐metastatic HCC cell line. However, the knockdown of RNPEP in exosomes from high‐metastatic HCC cells abated the changes described above. Animal studies in vivo highlighted the pro‐tumor and pro‐metastatic effects of exosomal RNPEP on MHCC‐97L cells by inducing CAF activation. Furthermore, tumor‐derived exosomal RNPEP induced the activation of NF‐κB signaling in MRC‐5 cells, a critical pathway associated with CAF activation. Collectively, these results provide novel insight into tumor‐derived exosomal RNPEP for its crosstalk with CAFs during HCC lung metastasis. This study demonstrates a novel mechanism underlying the communications between high‐metastatic HCC cells, CAFs, and low‐metastatic HCC cells. The tumor‐derived exosomal RNPEP, which induced the activation of CAFs to promote HCC lung metastatic progression, could be a potential target for further development of HCC therapeutic strategies.

Background The orchids of the subtribe Coelogyninae are among the most morphologically diverse and economically important groups within the subfamily Epidendroideae. Previous molecular studies have revealed that Coelogyninae is an unambiguously monophyletic group. However, intergeneric and infrageneric relationships within Coelogyninae are largely unresolved. There has been long controversy over the classification among the genera within the subtribe. Results The complete chloroplast (cp.) genomes of 15 species in the subtribe Coelogyninae were newly sequenced and assembled. Together with nine available cp. genomes in GenBank from representative clades of the subtribe, we compared and elucidated the characteristics of 24 Coelogyninae cp. genomes. The results showed that all cp. genomes shared highly conserved structure and contained 135 genes arranged in the same order, including 89 protein-coding genes, 38 tRNAs, and eight rRNAs. Nevertheless, structural variations in relation to particular genes at the IR/SC boundary regions were identified. The diversification pattern of the cp. genomes showed high consistency with the phylogenetic placement of Coelogyninae. The number of different types of SSRs and long repeats exhibited significant differences in the 24 Coelogyninae cp. genomes, wherein mononucleotide repeats (A/T), and palindromic repeats were the most abundant. Four mutation hotspot regions ( ycf1a , ndhF-rp132 , psaC-ndhE , and rp132-trnL ) were determined, which could serve as effective molecular markers. Selection pressure analysis revealed that three genes ( ycf1a , rpoC2 and ycf2 genes) might have experienced apparent positive selection during the evolution. Using the alignments of whole cp. genomes and protein-coding sequences, this study presents a well-resolved phylogenetic framework of Coelogyninae. Conclusion The inclusion of 55 plastid genome data from a nearly complete generic-level sampling provide a comprehensive view of the phylogenetic relationships among genera and species in subtribe Coelogyninae and illustrate the diverse genetic variation patterns of plastid genomes in this species-rich plant group. The inferred relationships and informally recognized major clades within the subtribe are presented. The genetic markers identified here will facilitate future studies on the genetics and phylogeny of subtribe Coelogyninae.

As a specific force sensor, the tri-axis accelerometer is one of the core instruments in an inertial navigation system (INS). During navigation, its measurement error directly induces constant or alternating navigation errors of the same order of magnitude. Moreover, it also affects the estimation accuracy of gyro drift coefficients during the initial alignment and calibration, which will indirectly result in navigation errors accumulating over time. Calibration can effectively improve measurement accuracy of the accelerometer. Device-level calibration can identify all of the parameters in the error model, and the system-level calibration can accurately estimate part of these parameters. Combining the advantages of both the methods and making full use of the precise angulation of the space-stabilized platform, this paper proposes a three-stage accelerometer self-calibration technique that can be implemented directly in the space-stable INS. The device-level calibration is divided into two steps considering the large amount of parameters. The first step is coarse calibration, which identifies parameters except for the nonlinear terms, and the second step is fine calibration, which not only identifies the nonlinear parameters, but also improves the accuracy of the parameters identified in the first step. The follow-on system-level calibration is carried out on part of the parameters using specific force error and attitude error to further improve the calibration accuracy. Simulation result shows that by using the proposed three-stage calibration technique in the space-stable INS, the estimation accuracy of accelerometer error can reach 1 × 10 − 6   g order of magnitude. Experiment results show that after the three-stage calibration, the accuracy of latitude, longitude, and attitude angles has increased by over 45% and the accuracy of velocity has increased by over 22% during navigation.

Due to the unique heterogeneity of neuroblastoma, its treatment and prognosis are closely related to the biological behavior of the tumor. However, the effect of the tumor immune microenvironment on neuroblastoma needs to be investigated, and there is a lack of biomarkers to reflect the condition of the tumor immune microenvironment. The GEO Database was used to download transcriptome data (both training dataset and test dataset) on neuroblastoma. Immunity scores were calculated for each sample using ssGSEA, and hierarchical clustering was used to categorize the samples into high and low immunity groups. Subsequently, the differences in clinicopathological characteristics and treatment between the different groups were examined. Three machine learning algorithms (LASSO, SVM-RFE, and Random Forest) were used to screen biomarkers and synthesize their function in neuroblastoma. In the training set, there were 362 samples in the immunity_L group and 136 samples in the immunity_H group, with differences in age, MYCN status, etc. Additionally, the tumor microenvironment can also affect the therapeutic response of neuroblastoma. Six characteristic genes (BATF, CXCR3, GIMAP5, GPR18, ISG20, and IGHM) were identified by machine learning, and these genes are associated with multiple immune-related pathways and immune cells in neuroblastoma. BATF, CXCR3, GIMAP5, GPR18, ISG20, and IGHM may serve as biomarkers that reflect the conditions of the immune microenvironment of neuroblastoma and hold promise in guiding neuroblastoma treatment.

Osteoporosis (OP) frequently coexists with rheumatoid arthritis (RA), but validated predictors of early risk are not extensively studied. This study seeks to examine the relationship between the neutrophil percentage-to-albumin ratio (NPAR) and the likelihood of developing RA-related OP(RA-OP). After investigating the relationship between the NPAR and RA-OP in the clinical retrospective study, we further validated this association using data from the National Health and Nutrition Examination Survey (NHANES) database (2005-2020 cycles). This retrospective study enrolled 718 RA patients from the Rheumatology Department of the First Affiliated Hospital of Guangzhou University of Chinese Medicine between January 2020 and December 2024. Patients were categorized into low-NPAR (<1.7598) and high-NPAR (≥1.7598) groups based on the median NPAR. Extracted clinical data encompassed demographic characteristics, comorbidities, serological markers, and other laboratory parameters. Preliminary univariate and multivariate logistic regression analyses assessed potential associations between NPAR and RA-OP, multi-model adjusted logistic regression was subsequently applied to evaluate the independent association, subgroup analyses examined consistency across demographic and clinical strata, Receiver operating characteristic (ROC) curve analysis assessed NPAR's diagnostic performance, and then Restricted cubic splines (RCS) visualized potential non-linear relationships. Finally using the identical statistical framework, we validated findings within the NHANES cohort. The high-NPAR group exhibited significantly higher OP incidence than the low-NPAR group (39.0% vs. 26.5%; P<0.001). After full adjustment (Model 4), NPAR remained independently associated with increased RA-OP risk as a categorical variable (high vs. low NPAR: adjusted OR = 1.70 (95%CI: 1.01~2.88); P = 0.049). Subgroup analyses demonstrated no significant interaction effects (P-interaction>0.05) except for disease duration. The ROC curve showed an Area Under the Curve(AUC) of 0.58 (95%CI: 0.53~0.63) and NPAR cut-off of 1.886. The covariate-adjusted RCS indicated a linear dose-response relationship (P overall=0.033; P nonlinearity=0.168). NHANES cohort analysis independently validated both the NPAR-RA-OP association and its linear characteristic. NPAR, serving as a novel composite biomarker integrating neutrophil-mediated inflammation and nutritional status (via albumin), independently predicts OP risk in RA. Its derivation from routine clinical parameters renders NPAR a readily deployable, cost-effective tool for OP risk stratification in clinical practice.

Sex-specific responses to mycorrhiza have been reported in dioecious plant species, but little attention has been paid to the influence of arbuscular mycorrhizal (AM) fungi on competitive ability under intersexual competition. To further address whether this competition is affected by an additional AM fungi supply, saplings were chosen and subjected to two mycorrhizal treatments [inoculated and non-inoculated (control) with an additional AM fungi ] while growing with the opposite sex for 3 months. Compared with the control, the additional AM fungi inoculation induced . saplings to exhibit significant sexual differences in root structure and nutrient uptake (e.g., cortical layer, cross-section area, radius of root tips, and N, K, and Mg content), and enlarged sexual differences in morphology and biomass accumulation (e.g., leaf number increment, shoot height increment, total leaf area, total specific root length, stem dry mass, leaf dry mass, and total dry mass). Meanwhile, inoculated females presented higher values in most of these traits mentioned above than males under intersexual competition. Therefore, we conclude that the intersexual competition can be increased by an additional AM fungi supply, with females gaining more symbiosis-mediated benefits than males.

Aim To describe the frequencies of physiologic monitor clinical alarms and to investigate nurses' perceptions and practices regarding clinical alarms in ICUs. Design A descriptive study. Methods A 24‐h continuous nonparticipant observation study was conducted in ICU. Observers observed and recorded the occurrence time, detail information when electrocardiogram monitor alarms triggered. And a cross‐sectional study was conducted among ICU nurses by convenience sampling, using the general information questionnaire and the Chinese version of clinical alarms survey questionnaire for medical devices. Data analysis was performed using SPSS 23. Results A total of 13,829 physiologic monitor clinical alarms were recorded in 14‐day observation and 1191 ICU nurses responded to the survey. Most nurses agreed or strongly agreed the sensitivity to alarms and responded quickly (81.28%), smart alarm systems (74.56%), alarm notification systems (72.04%) and set up alarm administrators (59.45%) were useful to improve alarm management, while frequent nuisance alarms disrupted patients care (62.47%) and reduced nurses' trust in alarms (49.03%), environmental noise interfered with nurses' recognition of the alarms (49.12%) and not everyone received education of alarm systems (64.65%). Conclusions Physiological monitor alarms occur frequently in ICU, and it is necessary to formulate or further optimize alarm management measures. It is recommended to use smart medical devices and alarm notification systems, formulate and implement standardized alarm management policies and norms, and strengthen alarm management education and training, so as to improve the nursing quality and patient safety. Patient or Public Contribution The patients in the observation study included all patients admitted to the ICU during the observation period. The nurses in the survey study were conveniently selected through an online survey.

The gravity disturbance vector is one of the major error sources in high-precision and long-term inertial navigation applications. Specific to the inertial navigation systems (INSs) with high-order horizontal damping networks, analyses of the error propagation show that the gravity-induced errors exist almost exclusively in the horizontal channels and are mostly caused by deflections of the vertical (DOV). Low-frequency components of the DOV propagate into the latitude and longitude errors at a ratio of 1:1 and time-varying fluctuations in the DOV excite Schuler oscillation. This paper presents two gravity compensation methods using the Earth Gravitational Model 2008 (EGM2008), namely, interpolation from the off-line database and computing gravity vectors directly using the spherical harmonic model. Particular attention is given to the error contribution of the gravity update interval and computing time delay. It is recommended for the marine navigation that a gravity vector should be calculated within 1 s and updated every 100 s at most. To meet this demand, the time duration of calculating the current gravity vector using EGM2008 has been reduced to less than 1 s by optimizing the calculation procedure. A few off-line experiments were conducted using the data of a shipborne INS collected during an actual sea test. With the aid of EGM2008, most of the low-frequency components of the position errors caused by the gravity disturbance vector have been removed and the Schuler oscillation has been attenuated effectively. In the rugged terrain, the horizontal position error could be reduced at best 48.85% of its regional maximum. The experimental results match with the theoretical analysis and indicate that EGM2008 is suitable for gravity compensation of the high-precision and long-term INSs.