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Abstract Background Osteoarthritis (OA) is a common joint disease that leads to chronic pain and functional limitations. Recent research has revealed soluble fibroblast activation protein (FAP) secreted from OA synovium could degrade type II collagen (Col2) in cartilage to promote the progression of OA. This study aimed to reveal the role of FAP from chondrocytes in OA and develop a novel lipid nanoparticle (LNP)-FAP siRNA delivery system for OA treatment. Methods The expression of FAP in the cartilage of knee OA patients was investigated using [68 Ga]Ga-FAPI-04 PET in vivo and immunofluorescence, western blotting, and RT-qPCR in vitro. Cell senescence was determined by senescence-associated β-galactosidase (SA-β-Gal) assay after FAP overexpressing or knockdown in chondrocytes. An OA model with chondrocyte-specific FAP knockout mice was applied to investigate the role of FAP in chondrocyte senescence and OA development. The therapeutic effects of lipid nanoparticle (LNP) @FAP siRNA on cartilage degeneration were evaluated in the rat OA model. Results Our study found that higher [68 Ga]Ga-FAPI-04 uptake was detected in knee OA patients by PET/CT scan. FAP mRNA and protein levels were highly expressed in OA-damaged cartilage. Moreover, we found that overexpression of FAP promotes chondrocyte senescence, and the genetic knockout of FAP in chondrocytes alleviates OA. Knockdown FAP by siRNA could alleviate chondrocyte senescence and suppress the NF-κB pathway to reduce the senescence-associated secretory phenotype (SASP). In the rat model of OA, intraarticular injection of LNP@FAP siRNA can reduce senescent cells and ameliorate cartilage destruction. Conclusion FAP-positive chondrocytes play a significant role in the pathogenesis of OA. Targeting these cells selectively has the potential to mitigate the progression of the disease. Our study provides valuable insights into the intraarticular injection of LNP@FAP siRNA as a promising strategy for the treatment of OA. Graphical abstract

Objective The transverse tibial transfer technique is employed primarily to treat diabetic foot ulcers (DFUs), aiming to enhance leg circulation and promote new blood vessel growth. This technique is also beneficial for various conditions associated with poor blood flow in the lower extremities. However, there is no clear molecular mechanism to explain the relationship between the transverse tibial transfer technique and angiogenesis in patients with diabetic foot. This study aims to preliminarily explore the change of IL‐6 and related cytokines in promoting angiogenesis during transverse tibial transplantation, providing a direction for future research. Methods We retrospectively assessed a study from April 2022 to November 2023 on 76 patients with severe DFUs at Wagner stages 3–4. Flow cytometry was used to detect the levels of 12 cytokines in serum before the operation and 3, 7, 14, 21, and 35 days after the operation. Ankle‐brachial index (ABI), transcutaneous oxygen tension (TcPO2), and glycosylated hemoglobin (Hba1c) were recorded at admission and discharge. We examined the variations in cytokine levels, wound healing duration, amputation rates, infection incidence, and other key outcomes. Results In our investigation, a total of 76 individuals participated, comprising 49 males and 27 females. These subjects had an average age of 64.7 years, with a standard deviation of 13 years. The mean ulcer healing time was 74 ± 31 days, amputation occurred in 3 patients, pin tract infection occurred in one patient (1.3%), and incision infection occurred in one patient (1.3%). By day 35 following the surgery, both the ABI and TcPO2 values showed a significant increase from their preoperative levels. HbA1c significantly improved compared with presurgery (p

Abstract Membrane budding, which underlies fundamental processes like endocytosis, intracellular trafficking, and viral infection, is thought to involve membrane coat-forming proteins, including the most observed clathrin, to form Ω-shape profiles and helix-forming proteins like dynamin to constrict Ω-profiles’ pores and thus mediate fission. Challenging this fundamental concept, we report that polymerized clathrin is required for Ω-profiles’ pore closure and that clathrin around Ω-profiles’ base/pore region mediates pore constriction/closure in neuroendocrine chromaffin cells. Mathematical modeling suggests that clathrin polymerization at Ω-profiles’ base/pore region generates forces from its intrinsically curved shape to constrict/close the pore. This new fission function may exert broader impacts than clathrin’s well-known coat-forming function during clathrin (coat)-dependent endocytosis, because it underlies not only clathrin (coat)-dependent endocytosis, but also diverse endocytic modes, including ultrafast, fast, slow, bulk, and overshoot endocytosis previously considered clathrin (coat)-independent in chromaffin cells. It mediates kiss-and-run fusion (fusion pore closure) previously considered bona fide clathrin-independent, and limits the vesicular content release rate. Furthermore, analogous to results in chromaffin cells, we found that clathrin is essential for fast and slow endocytosis at hippocampal synapses where clathrin was previously considered dispensable, suggesting clathrin in mediating synaptic vesicle endocytosis and fission. These results suggest that clathrin and likely other intrinsically curved coat proteins are a new class of fission proteins underlying vesicle budding and fusion. The half-a-century concept and studies that attribute vesicle-coat contents’ function to Ω-profile formation and classify budding as coat-protein (e.g., clathrin)-dependent or -independent may need to be re-defined and re-examined by considering clathrin’s pivotal role in pore constriction/closure.

Abstract Background and research objectives Given the enduring popularity of higher education, there has been considerable attention on the correlation between college students’ engagement in sports and their academic stress levels. This study seeks to delve deeply into how university physical education fosters academic performance by influencing students’ sports interests, particularly in enhancing their psychological resilience to mitigate academic pressure. Through this investigation, the aim is to offer both theoretical underpinnings and empirical evidence to support the holistic enhancement of higher education. Research methods Initially, this study undertakes an analysis of the fundamental relationship between college students’ physical activities and their experience of academic stress. Subsequently, utilizing a structural equation model, specific research models and hypotheses are formulated. These are then examined in detail through the questionnaire method to elucidate the mechanism by which college sports interests alleviate academic stress. Research findings The study reveals a significant positive correlation between psychological resilience and academic stress, indicating that a robust psychological resilience can effectively diminish academic pressure. Furthermore, both the sports atmosphere and sports interest are found to exert a notable positive impact on academic stress, mediated by the variable of psychological toughness. This underscores the pivotal role of physical education in fostering positive psychological traits and enhancing academic achievement. Conclusion This study underscores the central importance of cultivating and nurturing college students’ sports interests, as well as fostering a conducive sports atmosphere, in fortifying psychological resilience and mitigating academic pressure. By offering novel perspectives and strategies for alleviating the academic stress faced by college students, this study contributes valuable theoretical insights and practical experiences to the broader development of higher education.

Abstract Background and Aims For patients with high‐risk non‐ST elevation myocardial infarction (NSTEMI), current guidelines recommend an early invasive strategy within 24 h. New‐onset acute ischemic stroke (NAIS) is a rare but fatal complication of percutaneous coronary intervention (PCI). However, the effect of the timing of PCI and the risk of NAIS in NSTEMI is poorly defined. Methods Patients with NSTEMI who underwent PCI were queried from the National Inpatient Sample Database (2016–2019) and stratified into three groups: early (72 h) PCI. Multivariate logistic regression models were used to determine the association between timing of PCI and NAIS. Results Among 633,115 weighted hospitalizations, patients in the late PCI group had a higher incidence of NAIS (1.3%) than those in the early (0.67%) and medium (0.71%) PCI groups. Patients undergoing late PCI were older, more likely to be female, and had a greater incidence of comorbidities (e.g., diabetes mellitus, chronic pulmonary and renal illness, and atrial fibrillation) than those undergoing early or medium PCI. After adjustment, only late PCI was significantly associated with a 54% increased NAIS risk (adjusted odds ratio: 1.54 [95% confidence interval: 1.29–1.84]). Additionally, there was heterogeneity in the magnitude of risk by age and sex. Younger people (

Objective To investigate the correlation between heart rate variability (HRV) and the degree of nervousness before blood donation. Methods The psychological state of 253 blood donors before blood donation was assessed by the self-rating anxiety scale (SAS) and the degree of nervousness and their HRV were measured. The correlation between the SAS score, the degree of nervousness and the HRV parameters was analyzed, and the differences were compared among different types of donors by multivariate linear regression. Results A total of 247 blood donors were included in the study. Five HRV parameters in blood donors aged 18-24 were higher than in those aged 25 years and above(all P

The present study aimed to investigate the ameliorative effects of lysolecithin on fish stearin oil, meanwhile comparing the application of two different forms (lysolecithin powder and lysolecithin oil) and three inclusion levels (0.25, 0.75, 1.25 g kg−1) in largemouth bass. The entire study consisted of a 28-day digestibility trial and a consequent 68-day feeding experiment. Eight iso-nitrogenous (∼ 500 g kg−1) and iso-energetic (∼ 22 MJ kg−1) diets with high lipid level (∼ 170 g kg−1) were formulated to contain the same level of two different types of lysolecithin, and namely WFO (130 g kg−1 winterized fish oil), FSO (130 g kg−1 fish stearin oil), LLP (FSO + 1 g kg−1 lysolecithin powder, purity 250 g kg−1), MLP (FSO + 3 g kg−1 lysolecithin powder), HLP (FSO + 5 g kg−1 lysolecithin powder), LLO (FSO + 0.625 g kg−1 lysolecithin oil, purity 400 g kg−1), MLO (FSO + 1.875 g kg−1 lysolecithin oil) and HLO (FSO + 3.125 g kg−1 lysolecithin oil), respectively. Largemouth bass fed FSO showed lower apparent digestibility coefficients (ADCs) of nutrients (total fat, crude protein, gross energy, total amino acid, total essential amino acid) than the WFO. Without considering the lysolecithin type, medium and high doses (0.75, 1.25 g kg−1) significantly increased ADCs of nutrients compared with the 0.25 g kg−1 supplementation level. Lysolecithin oil significantly increased ADCs of nutrients than the lysolecithin powder. Thus, lysolecithin oil was chosen for 68-day feeding trial, and results showed the highest FBW, FI, WGR and SGR were recorded in diet HLO, and significantly higher than the FSO, LLO and MLO. Diet MLO significantly decreased lipid and energy in whole-body and lipid retention compared with the FSO, LLO and HLO. In addition, activity and mRNA expression of adipose triglyceride lipase significantly increased, while glycerol-3-phosphate acyltransferase 4 decreased in diet HLO.

BackgroundLymph node metastasis (LNM) is an important prognostic factor for cervical cancer (CC) and determines the treatment strategy. Hematological indicators have been reported as being useful biomarkers for the prognosis of a variety of cancers. This study aimed to evaluate the feasibility of machine learning models characterized by preoperative hematological indicators to predict the LNM status of CC patients before surgery.MethodsThe clinical data of 236 patients with pathologically confirmed CC were retrospectively analyzed at the Gynecology Oncology Department of the First Affiliated Hospital of Bengbu Medical University from November 2020 to August 2022. The least absolute shrinkage and selection operator (LASSO) was used to select 21 features from 35 hematological indicators and for the construction of 6 machine learning predictive models, including Adaptive Boosting (AdaBoost), Gaussian Naive Bayes (GNB), and Logistic Regression (LR), as well as Random Forest (RF), Support Vector Machines (SVM), and Extreme Gradient Boosting (XGBoost). Evaluation metrics of predictive models included the area under the receiver operating characteristic curve (AUC), accuracy, specificity, sensitivity, and F1-score.ResultsRF has the best overall predictive performance for ten-fold cross-validation in the training set. The specific performance indicators of RF were AUC (0.910, 95% confidence interval [CI]: 0.820–1.000), accuracy (0.831, 95% CI: 0.702–0.960), specificity (0.835, 95% CI: 0.708–0.962), sensitivity (0.831, 95% CI: 0.702–0.960), and F1-score (0.829, 95% CI: 0.696–0.962). RF had the highest AUC in the testing set (AUC = 0.854).ConclusionRF based on preoperative hematological indicators that are easily available in clinical practice showed superior performance in the preoperative prediction of CC LNM. However, investigations on larger external cohorts of patients are required for further validation of our findings.

Background and objectivesUpwards of 50% of acute ischemic stroke (AIS) survivors endure varying degrees of disability, with a recurrence rate of 17.7%. Thus, the prediction of outcomes in AIS may be useful for treatment decisions. This study aimed to determine the applicability of a machine learning approach for forecasting early outcomes in AIS patients.MethodsA total of 659 patients with new-onset AIS admitted to the Department of Neurology of both the First and Second Affiliated Hospitals of Bengbu Medical University from January 2020 to October 2022 included in the study. The patient’ demographic information, medical history, Trial of Org 10,172 in Acute Stroke Treatment (TOAST), National Institute of Health Stroke Scale (NIHSS) and laboratory indicators at 24 h of admission data were collected. The Modified Rankine Scale (mRS) was used to assess the 3-mouth outcome of participants’ prognosis. We constructed nine machine learning models based on 18 parameters and compared their accuracies for outcome variables.ResultsFeature selection through the Least Absolute Shrinkage and Selection Operator cross-validation (Lasso CV) method identified the most critical predictors for early prognosis in AIS patients as white blood cell (WBC), homocysteine (HCY), D-Dimer, baseline NIHSS, fibrinogen degradation product (FDP), and glucose (GLU). Among the nine machine learning models evaluated, the Random Forest model exhibited superior performance in the test set, achieving an Area Under the Curve (AUC) of 0.852, an accuracy rate of 0.818, a sensitivity of 0.654, a specificity of 0.945, and a recall rate of 0.900.ConclusionThese findings indicate that RF models utilizing general clinical and laboratory data from the initial 24 h of admission can effectively predict the early prognosis of AIS patients.

Prostate Cancer Associated 3 (PCA3) as a promising biomarker to replace serum prostate-specific antigen (PSA) for differential diagnosis of benign and malignant prostate diseases. However, the detection of PCA3 in urine requires the collection of digital rectal examination (DRE) urine, which limits the application of PCA3 in screening prostate diseases. In the present study, a new reverse transcription quantitative real-time polymerase chain reaction (qRT-PCR) method was developed for PCA3 detection in non-DRE urine. The method uses the nanomaterial Graphene oxide (GO) to effectively prevent nonspecific amplification in qRT-PCR. GO-based qRT-PCR produced no nonspecific amplification. Receiver operating characteristic curve (ROC) results showed that the area under curve (AUC) of PCA3 to discriminate normal control subjects from prostate cancer (PCa) was 0.869 (95% confidence interval [CI], 0.689–1.000), and using 2.711 as the cutoff value of PCA3, the sensitivity was 81.8% and the specificity was as high as 88.9%. For prostatitis (PTIS) and PCa, the AUC value of PCA3 to distinguish them was 0.636 (95% CI, 0.396–0.877), with 81.8% sensitivity and 58.3% specificity. Compared with the 8.3% specificity of PAS, the specificity of PCA3 was improved by 50%, which suggested that PCA3, in non-DRE urine, has a significant potential application in the differential diagnosis of prostate diseases.

Abstract Background Nowadays, both lateral mass screw (LMS) and pedicle screw were effective instrumentation for posterior stabilization of cervical spine. This study aims to evaluate the feasibility of a new free-hand technique of C7 pedicle screw insertion without fluoroscopic guidance for cervical spondylotic myelopathy (CSM) patients with C3 to C6 instrumented by lateral mass screws. Methods A total of 53 CSM patients underwent lateral mass screws instrumentation at C3 to C6 levels and pedicle screw instrumentation at C7 level were included. The preoperative 3-dimenional computed tomography (CT) reconstruction images of cervical spine were used to determine 2 different C7 pedicle screw trajectories. Trajectory A passed through the axis of the C7 pedicle while trajectory B selected the midpoint of the base of C7 superior facet as the entry point. All these 53 patients had the C7 pedicle screw inserted through trajectory B by free-hand without fluoroscopic guidance and the postoperative CT images were obtained to evaluate the accuracy of C7 pedicle screw insertion. Results Trajectory B had smaller transverse angle, smaller screw length, and smaller screw width but both similar sagittal angle and similar pedicle height when compared with trajectory A. A total of 106 pedicle screws were inserted at C7 through trajectory B and only 8 screws were displaced with the accuracy of screw placement as high as 92.5%. Conclusion In CSM patients with C3 to C6 instrumented by LMS, using trajectory B for C7 pedicle screw insertion is easy to both identify the entry point and facilitate the rod insertion.

Abstract The benign and malignant status of solitary pulmonary nodules (SPNs) is a key determinant of treatment decisions. The main objective of this study was to validate the efficacy of machine learning (ML) models featured with dual-layer detector spectral computed tomography (DLCT) parameters in identifying the benign and malignant status of SPNs. 250 patients with pathologically confirmed SPN were included in this study. 8 quantitative and 16 derived parameters were obtained based on the regions of interest of the lesions on the patients’ DLCT chest enhancement images. 6 ML models were constructed from 10 parameters selected after combining the patients' clinical parameters, including gender, age, and smoking history. The logistic regression model showed the best diagnostic performance with an area under the receiver operating characteristic curve (AUC) of 0.812, accuracy of 0.813, sensitivity of 0.750 and specificity of 0.791 on the test set. The results suggest that the ML models based on DLCT parameters are superior to the traditional CT parameter models in identifying the benign and malignant nature of SPNs, and have greater potential for application.

Abstract Discovery of new small molecules that can activate distinct programmed cell death pathway is of significant interest as a research tool and for the development of novel therapeutics for pathological conditions such as cancer and infectious diseases. The small molecule raptinal was discovered as a pro-apoptotic compound that can rapidly trigger apoptosis by promoting the release of cytochrome c from the mitochondria and subsequently activating the intrinsic apoptotic pathway. As raptinal is very effective at inducing apoptosis in a variety of different cell types in vitro and in vivo, it has been used in many studies investigating cell death as well as the clearance of dying cells. While examining raptinal as an apoptosis inducer, we unexpectedly identified that in addition to its pro-apoptotic activities, raptinal can also inhibit the activity of caspase-activated Pannexin 1 (PANX1), a ubiquitously expressed transmembrane channel that regulates many cell death-associated processes. By implementing numerous biochemical, cell biological and electrophysiological approaches, we discovered that raptinal can simultaneously induce apoptosis and inhibit PANX1 activity. Surprisingly, raptinal was found to inhibit cleavage-activated PANX1 via a mechanism distinct to other well-described PANX1 inhibitors such as carbenoxolone and trovafloxacin. Furthermore, raptinal also interfered with PANX1-regulated apoptotic processes including the release of the ‘find-me’ signal ATP, the formation of apoptotic cell-derived extracellular vesicles, as well as NLRP3 inflammasome activation. Taken together, these data identify raptinal as the first compound that can simultaneously induce apoptosis and inhibit PANX1 channels. This has broad implications for the use of raptinal in cell death studies as well as in the development new PANX1 inhibitors.

Three-dimensional object detection has been substantially improved with the use of expensive LiDAR and stereo vision systems in intelligent driving. The less-expensive and more scalable solution of monocular 3D object detection, however, remains a key challenge. This study primarily explores real-time pseudo 3D object detection with monocular vision and designs a single-shot RPN model, VKP-P3D, which relies purely on visual feature extraction. Through a multiscale feature fusion and an attention mechanism module, this model obtains high-dimensional feature representations during the feature extraction phase. In the detection head of the VKP-P3D model, the pseudo 3D object detection is obtained by regressing 2D bounding box and the visible key points within the image coordinate of the 3D box from the camera’s perspective. Finally, assuming flat ground and considering geometric parameters of the camera, the object’s 3D information can be extracted. To verify the effectiveness of the proposed algorithm, we constructed two pseudo 3D object detection datasets based on visible key points and compared with current state-of-the-art real-time object detector. Results showed that the proposed model has high detection accuracy and speed.

Abstract The functionally pleiotropic ectoenzyme CD38 is a glycohydrolase widely expressed on immune and non-hematopoietic cells. By converting NAD+ to ADP-ribose and nicotinamide, CD38 governs organismal NAD+ homeostasis and the activity of NAD+-dependent cellular enzymes. CD38 has emerged as a major driver of age-related NAD+ decline underlying adverse metabolic states, frailty and reduced health span. CD38 is upregulated in systemic sclerosis (SSc), a chronic disease characterized by fibrosis in multiple organs. We sought to test the hypothesis that inhibition of the CD38 ecto-enzymatic activity using a heavy-chain monoclonal antibody Ab68 will, via augmenting organismal NAD+, prevent fibrosis in a mouse model of SSc characterized by NAD+ depletion. Here we show that treatment of mice with a non-cytotoxic heavy-chain antibody that selectively inhibits CD38 ectoenzyme resulted in NAD+ boosting that was associated with significant protection from fibrosis in multiple organs. These findings suggest that targeted inhibition of CD38 ecto-enzymatic activity could be a potential pharmacological approach for SSc fibrosis treatment.

Oysters are notably susceptible to accumulating substantial amounts of cadmium (Cd), leading to food safety concerns, yet the molecular mechanisms are not fully understood. Previous study identified a significant correlation between polymorphisms in the Zip1 and Zip3 of Fujian oyster (Crassostrea angulata) and the levels of Cd accumulation. Zip1 and Zip3, belonging to the Zip family, are primarily responsible for the cellular transport of zinc and other metal ions. To delve deeper into their roles in Cd transport within oysters, this research cloned and analyzed the sequences of Fujian oyster Zip1 and Zip3. The open reading frames for Zip1 and Zip3 were 960 and 978 bp, respectively, encoding proteins of 319 and 325 amino acids. Following Cd exposure, the expression levels of these genes in the mantle, gills, and other tissues initially increased significantly before decreasing, demonstrating a dose-dependent response. The lowest expression levels were observed in the adductor muscle, with Zip1 reaching its highest expression in the mantle and Zip3 in the visceral mass. In vitro RNAi experiments revealed that silencing Zip1 led to a 1.26-fold decrease in new 113Cd accumulation in the mantle, whereas silencing Zip3 resulted in a 1.29-fold increase. Immunohistochemistry showed weak expression of Zip1 and Zip3 proteins in the connective tissue of the mantle. In summary, Zip1 and Zip3 in Fujian oyster can transport Cd as a substrate, and played different roles in the absorption and efflux of Cd.

ObjectiveDiabetic nephropathy (DN) is a major microvascular complication of diabetes and the leading cause of end-stage renal disease. Early detection and prevention of DN are important. Retinol-binding protein 4 (RBP4) has been considered as a single diagnostic marker for the detection of renal impairment. However, the results have been inconsistent. The present meta-analysis aimed to determine the diagnostic potential of RBP4 in patients in type 2 diabetes mellitus (T2DM) with DN.MethodsWe searched PubMed, Web of Science, Embase, Wanfang and CNKI databases from inception until January 2024. The meta-analysis was performed by Stata version 15.0, and sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR), diagnostic odds ratio (DOR) and area under the curve (AUC) were pooled. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was utilized to assess the quality of each included study. In addition, heterogeneity and publication bias were evaluated.ResultsTwenty-nine studies were included in the meta-analysis. The pooled sensitivity and specificity were 0.76 [95% confidence interval (CI), 0.71–0.80] and 0.81 (95% CI, 0.76–0.85), respectively. The results showed a pooled PLR of 4.06 (95% CI, 3.16–5.21), NLR of 0.29 (95% CI, 0.24–0.36) and DOR of 13.76 (95% CI, 9.29–20.37). The area under the summarized receiver operating characteristic curve was given a value of 0.85 (95% CI, 0.82–0.88). No obvious publication bias existed in the Deeks’ funnel plot asymmetry test.ConclusionOur findings suggest that RBP4 has a promising diagnostic value with good sensitivity and specificity for patients with T2DM with DN.

Abstract Wilms tumor (WT) is the most common pediatric renal malignant tumor in the world. Overall, the prognosis of Wilms tumor is very good. However, the prognosis of patients with anaplastic tumor histology or disease relapse is still poor, and their recurrence rate, metastasis rate and mortality are significantly increased compared with others. Currently, the combination of histopathological examination and molecular biology is essential to predict prognosis and guide the treatment. However, the molecular mechanism has not been well studied. Genetic profiling may be helpful in some way. Hence, we sought to identify novel promising biomarkers of WT by integrating bioinformatics analysis and to identify genes associated with the pathogenesis of WT. In the presented study, the NCBI Gene Expression Omnibus was used to download two datasets of gene expression profiles related to WT patients for the purpose of detecting overlapped differentially expressed genes (DEGs). The DEGs were then uploaded to DAVID database for enrichment analysis. In addition, the functional interactions between proteins were evaluated by simulating the protein–protein interaction (PPI) network of DEGs. The impact of selected hub genes on survival in WT patients was analyzed by using the online tool R2: Genomics Analysis and Visualization Platform. The correlation between gene expression and the degree of immune infiltration was assessed by the Estimation of Stromal and Immune cells in Malignant Tumor tissues using the Expression (ESTIMATE) algorithm and the single sample GSEA. Top 12 genes were identified for further study after constructing a PPI network and screening hub gene modules. Kinesin family member 2C (KIF2C) was identified as the most significant gene predicting the overall survival of WT patients. The expression of KIF2C in WT was further verified by quantitative real-time polymerase chain reaction and immunohistochemistry. Furthermore, we found that KIF2C was significantly correlated with immune cell infiltration in WT. Our present study demonstrated that altered expression of KIF2C may be involved in WT and serve as a potential prognostic biomarker for WT patients.

Oysters are a group of economically important bivalves in China, with estuaries serving as one of their primary cultivation areas. However, heavy metal pollution in these estuarine environments poses a potential threat to aquaculture by leading to the accumulation of heavy metals in farmed oysters, which could impact their safety and marketability. This study was conducted in the aquaculture area of the Luoyangjiang River estuary, where eight sampling sites were selected. Water, sediment, and oysters categorized by shell length were collected from each site. The concentrations of heavy metals (Ag, As, Cd, Cr, Cu, Ni, Pb, and Zn) were determined in both the environmental samples and oyster tissues. Additionally, multiplex species-specific PCR was used to identify oyster species. The results showed significant variations in dissolved-phase and suspended particulate matter (SPM) metal concentrations across different sampling sites, while sediment metal concentrations were more consistent but similar to those in SPM. The large oysters were comprised of 50% Magallana angulata and 50% Magallana gigas, while small oysters were identified as Magallana sikamea. The Cd, Cu, Pb, and Zn levels in both size groups of oysters exceeded data from previous studies, indicating contamination in the estuary. The observed differences in heavy metal concentrations between large and small oysters primarily reflect species-specific variability in metal accumulation, which may also be influenced by factors such as growth and exposure duration. Furthermore, the lack of significant correlation between metal concentrations in environmental media and oysters suggests that oysters may be exposed to multiple sources of metal contamination.

Agrobacterium sp. are notable for their ability to produce substantial amounts of exopolysaccharides. Our study identified an exopolysaccharide (Galacan, 4982.327 kDa) from Agrobacterium sp. FN01. Galacan is a heteropolysaccharide primarily composed of glucose and galactose at a molar ratio of 25:1. The FT-IR results suggested that Galacan had typical absorption peaks of polysaccharide. The results of periodate oxidation, Smith degradation, and NMR confirmed the presence of structural units, such as β-D-Galp(→, →3)β-D-Galp(1→, →2,3)β-D-Glcp(1→, β-D-Glcp(1→, and →2)β-D-Glcp(1→. Galacan demonstrated significant biological activities. In experiments conducted with zebrafish, it facilitated the proliferation of Lactobacillus brevis in the intestinal tract, suggesting potential prebiotic properties. Moreover, in vivo studies revealed its antihyperglycemic effects, as evidenced by significant reductions in blood glucose levels and enhanced fluorescence intensity of pancreatic β cells in a streptozotocin (STZ)-induced hyperglycemic zebrafish model. Additionally, antiaging assays demonstrated Galacan’s ability to inhibit β-galactosidase activity and enhance telomerase activity in a hydrogen peroxide (HP)-induced aging zebrafish model. These findings emphasized the potential of Galacan as a natural prebiotic with promising applications in diabetes prevention and antiaging interventions.

Abstract Purpose To analyze the clinical effects of different positions of the weight-bearing axis (WBA) after high tibial osteotomy (HTO). Methods The clinical data of 90 patients who underwent HTO in the Department of Orthopedics at our hospital from June 2018 to June 2021 were retrospectively analyzed. Patients were divided into groups A and B (n = 45 per group) according to different post-HTO WBA positions of the affected side. WBAs in both groups were at 50–60% and 62–66% of the tibial plateau, from inside to outside, respectively. American Hospital for Special Surgery Knee Score (HSS), visual analog scale (VAS) score, femorotibial angle (FTA), and medial proximal tibial angle (MPTA) were recorded and analyzed. Results All patients were followed up with for 12 months. HSS scores increased gradually and VAS scores decreased gradually in both groups preoperatively, and at 3 months, 6 months, and 1 year postoperatively (P 0.05). Postoperative MPTA and FTA were 89.56° ± 2.18° and 177.11° ± 2.63° in group A, and 89.07° ± 1.98° and 177.07° ± 2.36° in group B, respectively, with no significant between-group difference (P > 0.05). Conclusion Patients with post-HTO WBA ranges of 50–60% and 62–66% achieved knee joint function improvement and pain relief. Half a year later, those with a WBA range of 62–66% had better knee joint function scores. However, a comparison of long-term effects warrants further investigation.

Over-use or misuse of antibiotics in livestock and poultry production contributes to the rising threat of antibiotic resistance in animals and has negative ecological effects. Exopolysaccharides from lactic acid bacteria (LAB-EPS) are a class of biological macromolecules which are secreted by lactic acid bacteria to the outside of the cell wall during their growth and metabolism. Numerous studies demonstrated that LAB-EPS have anti-inflammatory and antimicrobial activities and are able to regulate intestinal health and the immune system in livestock. They are biodegradable, nontoxic and bio-compatible, which are considered as ideal alternatives to antibiotics. This review aims to discuss and summarize recent research findings of LAB-EPS on regulation of intestinal health and the immune system in animals, and thus provide scientific justification for commercial applications of LAB-EPS in livestock.

Wound healing has become one of the basic issues faced by the medical community because of the susceptibility of skin wounds to bacterial infection. As such, it is highly desired to design a nanocomposite hydrogel with excellent antibacterial activity to achieve high wound closure effectiveness. Here, based on ultrasound-triggered piezocatalytic therapy, a multifunctional hydrogel is designed to promote bacteria-infected wound healing. Under ultrasonic vibration, the surface of barium titanate (BaTiO3, BT) nanoparticles embedded in the hydrogel rapidly generate reactive oxygen species (ROS) owing to the established strong built-in electric field, endowing the hydrogel with superior antibacterial efficacy. This modality shows intriguing advantages over conventional photodynamic therapy, such as prominent soft tissue penetration ability and the avoidance of serious skin phototoxicity after systemic administration of photosensitizers. Moreover, the hydrogel based on N-[tris(hydroxymethyl)methyl]acrylamide (THM), N-(3-aminopropyl)methacrylamide hydrochloride (APMH) and oxidized hyaluronic acid (OHA) exhibits outstanding self-healing and bioadhesive properties able to accelerate full-thickness skin wound healing. Notably, compared with the widely reported mussel-inspired adhesive hydrogels, OHA/THM-APMH hydrogel due to the multiple hydrogen bonds from unique tri-hydroxyl structure overcomes the shortage that catechol groups are easily oxidized, giving it long-term and repeatable adhesion performance. Importantly, this hybrid hydrogel confines BT nanoparticles to wound area and locally induced piezoelectric catalysis under ultrasound to eradicate bacteria, markedly improving the therapeutic biosafety and exhibits great potential for harmless treatment of bacteria-infected tissues.

BackgroundThe occurrence of lymph node metastasis (LNM) is one of the critical factors in determining the staging, treatment and prognosis of cervical cancer (CC). Heart rate variability (HRV) is associated with LNM in patients with CC. The purpose of this study was to validate the feasibility of machine learning (ML) models constructed with preoperative HRV as a feature of CC patients in predicting CC LNM.MethodsA total of 292 patients with pathologically confirmed CC admitted to the Department of Gynecological Oncology of the First Affiliated Hospital of Bengbu Medical University from November 2020 to September 2023 were included in the study. The patient’ preoperative 5-min electrocardiogram data were collected, and HRV time-domain, frequency-domain and non-linear analyses were subsequently performed, and six ML models were constructed based on 32 parameters. Model performance was assessed using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity.ResultsAmong the 6 ML models, the random forest (RF) model showed the best predictive performance, as specified by the following metrics on the test set: AUC (0.852), accuracy (0.744), sensitivity (0.783), and specificity (0.785).ConclusionThe RF model built with preoperative HRV parameters showed superior performance in CC LNM prediction, but multicenter studies with larger datasets are needed to validate our findings, and the physiopathological mechanisms between HRV and CC LNM need to be further explored.

BackgroundLaparoscopic total mesorectal excision (LaTME) is standard surgical methods for rectal cancer, and LaTME operation is a challenging procedure. This study is intended to use machine learning to develop and validate prediction models for surgical difficulty of LaTME in patients with rectal cancer and compare these models’ performance.MethodsWe retrospectively collected the preoperative clinical and MRI pelvimetry parameter of rectal cancer patients who underwent laparoscopic total mesorectal resection from 2017 to 2022. The difficulty of LaTME was defined according to the scoring criteria reported by Escal. Patients were randomly divided into training group (80%) and test group (20%). We selected independent influencing features using the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression method. Adopt synthetic minority oversampling technique (SMOTE) to alleviate the class imbalance problem. Six machine learning model were developed: light gradient boosting machine (LGBM); categorical boosting (CatBoost); extreme gradient boost (XGBoost), logistic regression (LR); random forests (RF); multilayer perceptron (MLP). The area under receiver operating characteristic curve (AUROC), accuracy, sensitivity, specificity and F1 score were used to evaluate the performance of the model. The Shapley Additive Explanations (SHAP) analysis provided interpretation for the best machine learning model. Further decision curve analysis (DCA) was used to evaluate the clinical manifestations of the model.ResultsA total of 626 patients were included. LASSO regression analysis shows that tumor height, prognostic nutrition index (PNI), pelvic inlet, pelvic outlet, sacrococcygeal distance, mesorectal fat area and angle 5 (the angle between the apex of the sacral angle and the lower edge of the pubic bone) are the predictor variables of the machine learning model. In addition, the correlation heatmap shows that there is no significant correlation between these seven variables. When predicting the difficulty of LaTME surgery, the XGBoost model performed best among the six machine learning models (AUROC=0.855). Based on the decision curve analysis (DCA) results, the XGBoost model is also superior, and feature importance analysis shows that tumor height is the most important variable among the seven factors.ConclusionsThis study developed an XGBoost model to predict the difficulty of LaTME surgery. This model can help clinicians quickly and accurately predict the difficulty of surgery and adopt individualized surgical methods.

BackgroundSubacromial spurs are considered the one of the pathology underlying shoulder impingement syndrome. Furthermore, few studies have focused on the morphology of the subacromial spurs in normal Chinese people. This study aimed to study the spur distribution and to illustrate the morphology of spurs, which may help guide the extent of acromioplasty.MethodsA total of 93 normal individuals were enrolled, and both shoulders of all enrolled individuals were analyzed. The subjects were divided and classified into three different groups by ages: group I = 18-40 years, group II = 41-60 years, and group III ≥ 61 years. The osteophyte distribution, osteophyte area, subacromial surface area and osteophyte area/subacromial surface area ratio were measured and illustrated using Mimics and 3-matic software. The shape of the acromion was classified according to the Bigliani and Morrison classification system. The acromial angle was also classified. Then, the relationship between osteophytes, acromial classification and acromial angle was analyzed.ResultsType II (curved shape) was the most common type of acromion, and the hooked shape was a rare form. A significant increase in the left subacromial surface area in males was observed in group III compared with group I (P < 0.001) and group II (P = 0.004). The total spur/subacromial area ratio was significantly higher in group II than I. An obvious increase in the right subacromial area was observed in group III compared with group I (P = 0.004). Furthermore, there was a significant increase in the right spur area (P = 0.021) and total spur/subacromial area ratio (P = 0.006) in females in group II compared with group I. Fewer spurs were observed on the left than on the right side (p = 0.0482). One spur was most common among type II acromions (29/36) (80.56%) on the left side and the right side (34/52, 65.38%).ConclusionsSpurs osteophytes are mainly distributed with an irregular shape and mostly run through the medial and lateral sides of the subacromial surface in normal subjects. The characteristics of subacromial spurs are so diverse that a surgeon must conduct subacromial decompression completely based on the morphology of individual spurs.

ObjectiveDisruption in the delicate symphony of genes, microRNA (miRNA), or protein expression can result in the dysregulation of the immune system, leading to the devastating consequences such as lupus nephritis (LN). The capacity of exosomes to transport miRNAs between cells and modify the phenotype of recipient cells implies their involvement in persistent kidney inflammation. This study unveils identifying two previously undiscovered exosomal miRNAs in the serum of LN patients, offering potential solutions to the current challenges in LN diagnosis and management.MethodsInitially, we used a reagent-based kit to isolate serum exosomes from patients with Systemic lupus erythematosus (SLE) and used Trizol method for total RNA extraction. Subsequently, we employed small RNA sequencing to screen for differential expression profiles of exosomal small RNAs. The RT-qPCR method was used to individually validate samples in both the screening and validation cohorts, enabling the identification of candidate small RNAs; specific to LN. We assessed the diagnostic potency using receiver operating characteristic (ROC) curve, and explored the biological roles of miRNAs using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses.ResultsCompared to SLE patients without LN, SLE patients accompanied by LN exhibited significantly spiked levels of exosomal hsa-miR-4796-5p and hsa-miR-7974. The duo of miRNAs, hsa-miR-4796-5p and hsa-miR-7974, exhibited promising potential as biomarkers for diagnosing LN, with an AUC exceeding 0.8. Correlation analysis revealed a strong positive association between these miRNAs and proteinuria, as well as the SLE Disease Activity Index (SLEDAI) score. Moreover, the levels of two miRNAs in LN patients were significantly elevated in comparison to other autoimmune nephritis conditions, such as immunoglobulin A nephropathy (IgAN) and diabetic nephropathy (DN). Furthermore, the bioinformatics analysis indicated that this miRNAs duo can play a pivotal role in the regulation of immune processes by modulating signal pathways, such as the mTOR and PI3K-Akt signaling pathway.ConclusionThis study provides a new ground that serum exosomal miRNAs can effectively identify and predict LN in SLE patients.

Laser powder bed fusion (LPBF) is capable to process complex flow field structures on 316L stainless steel (316L SS) bipolar plates, which is promising to improve the performance of proton exchange membrane fuel cell (PEMFC). However, insufficient corrosion resistance and relatively high interfacial contact resistance (ICR) hinder the widespread of LPBF-processed 316L SS bipolar plates. In this work, active screen plasma nitriding (ASPN) was used to modify 316L SSs fabricated by the LPBF process and forging, respectively. Results showed that the nitrided layer of LPBF-processed 316L SS (2000 mm/s, 300 W) exhibited the highest surface nitrogen concentration, thickest nitrided layer and highest average hardness. The ICR values decreased significantly after ASPN treatment. The corrosion current of nitrided LPBF-processed 316L SS (2000 mm/s, 300 W) was much lower than that of the nitrided forged 316L SS. By comparing multiscale microstructures between LPBF-processed and forged 316L SS, the ASPN mechanism of LPBF-processed 316L SS was proposed.

Abstract We demonstrate a fiber Bragg grating (FBG) strain interrogator based on a scattering medium to generate stable and deterministic speckle patterns, calibrated with applied strain, which are highly dependent on the FBG back-reflection spectral components. The strong wavelength-dependency of speckle patterns was previously used for high resolution wavemeters where scattering effectively folds the optical path, but instability makes practical realization of such devices difficult. Here, a new approach is demonstrated by utilizing femtosecond laser-written scatterers inside flat optical fiber, to enhance mechanical stability. By inscribing 15 planes of pseudo-randomized nanovoids (714 $$\times$$ × 500 voids per plane) as a 3D array in a 1 $$\times$$ × 0.7 $$\times$$ × 0.16 mm volume, the intrinsic stability and compactness of the device was improved. Operating as a wavemeter, it remained stable for at least 60 h with 45 pm resolution over the wavelength range of 1040–1056 nm. As a reflection mode FBG interrogator, after calibrating speckle patterns by applying tensile strain to the FBG, the device is capable of detecting microstrain changes in the range of 0–200 $$\mu \epsilon$$ μ ϵ with a standard error of 4 $$\mu \epsilon$$ μ ϵ , limited by the translation stage step size. All these characteristics make it an interesting technology for filling the niche of low-cost, high-resolution wavemeters and interrogators which offer the best available trade-off between resolution, compactness, price and stability.

The purple-leaf phenotype in pak choi is due to the accumulation of anthocyanin. The main regulated genes are unclear. The gene controlling the purple-leaf phenotype was mapped on A03 using BSA-seq, but the candidate interval was not further narrowed with InDel markers. Based on our previous study, we hypothesized that the candidate gene that regulates purple leaves in pak choi may also be the Dark_Pur gene from B. juncea. Using the Dark_Pur-1 marker to identify P1, P2, F1, and F2, it was confirmed that the purple trait in purple-leaf pak choi was controlled by the Dark_Pur gene from B. juncea through distant hybridization. A DNA segment of approximately 514 Kb containing the Dark_Pur gene was reintroduced into pak choi from B. juncea. Meanwhile, a new purple pak choi germplasm line was created with green pak choi × purple B. juncea via distant hybridization, which proved that distant hybridization is an effective method for creating new germplasms. Furthermore, the purple-leaf phenotypes of 20 pak choi varieties were identified, and the purple-leaf traits of all lines were derived from B. juncea via distant hybridization. At present, few studies have focused on the background of the purple trait in pak choi; however, in this study, our results suggest that there is a high probability that the purple trait in pak choi may be completely derived from purple B. juncea via distant hybridization. This study also lays a good foundation for research on the creation of new germplasms through distant hybridization among the Brassica species.

IntroductionLow-grade glioma (LGG) is a prevalent malignant tumor in the intracranial region. Despite the advancements in treatment methods for this malignancy over the past decade, significant challenges still persist in the form of drug resistance and tumor recurrence. The Notch signaling pathway plays essential roles in many physiological processes as well as in cancer development. However, the significance of the pathway and family genes in LGG are poorly understood. MethodsWe conducted gene expression profiling analysis using the TCGA dataset to investigate the gene set associated with the Notch signaling pathway. we have proposed a metric called "NotchScore" that quantifies the strength of the Notch signaling pathway and enables us to assess its significance in predicting prognosis and immune response in LGG. We downregulated JAG1 in low-grade gliomas to assess its influence on the proliferation and migration of these tumors. Ultimately, we determined the impact of the transcription factor VDR on the transcription of PDL1 through chip-seq data analysis.ResultsOur findings indicate that tumors with a higher NotchScore, exhibit poorer prognosis, potentially due to their ability to evade the anti-tumor effects of immune cells by expressing immune checkpoints. Among the genes involved in the Notch signaling pathway, JAG1 has emerged as the most representative in terms of capturing the characteristics of both NotchScore and Notch pathways. The experimental results demonstrate that silencing JAG1 yielded a significant decrease in tumor cell proliferation in LGG cell lines. Our study revealed mechanisms by which tumors evade the immune system through the modulation of PDL1 transcription levels via the PI3K-Akt signaling pathway. Additionally, JAG1 potentially influences PDL1 in LGG by regulating the PI3K-Akt signaling pathway and the expression of the transcription factor VDR.DiscussionThese findings contribute to our understanding of immune evasion by tumors in LGG. The insights gained from this research may have implications for the development of therapeutic interventions for LGG.

Background: Prior research suggests that autonomic modulation investigated by heart rate variability (HRV) might act as a novel predictive biomarker for cancer prognosis, such as in breast cancer and pancreatic cancer. It is not clear whether there is a correlation between autonomic modulation and prognosis in patients with extensive-stage small cell lung cancer (ES-SCLC). Therefore, the purpose of the study was to examine the association between short-term HRV, deceleration capacity (DC) and acceleration capacity (AC) of heart rate and overall survival in patients with ES-SCLC.Methods: We recruited 40 patients with ES-SCLC, and 39 were included in the final analysis. A 5-min resting electrocardiogram of patients with ES-SCLC was collected using a microelectrocardiogram recorder to analyse short-term HRV, DC and AC. The following HRV parameters were used: standard deviation of the normal-normal intervals (SDNN) and root mean square of successive interval differences (RMSSD). Overall survival of patients with ES-SCLC was defined as time from the date of electrocardiogram measurement to the date of death or the last follow-up. Follow-up was last performed on 07 June 2023. There was a median follow-up time of 42.2 months.Results: Univariate analysis revealed that the HRV parameter SDNN, as well as DC significantly predicted the overall survival of ES-SCLC patients (all p < 0.05). Multivariate analysis showed that the HRV parameters SDNN (hazard ratio = 5.254, 95% CI: 1.817–15.189, p = 0.002), RMSSD (hazard ratio = 3.024, 95% CI: 1.093–8.372, p = 0.033), as well as DC (hazard ratio = 3.909, 95% CI: 1.353–11.293, p = 0.012) were independent prognostic factors in ES-SCLC patients.Conclusion: Decreased HRV parameters (SDNN, RMSSD) and DC are independently associated with shorter overall survival in ES-SCLC patients. Autonomic nervous system function (assessed based on HRV and DC) may be a new biomarker for evaluating the prognosis of patients with ES-SCLC.

BackgroundPrior research suggests that cardiovascular autonomic dysfunction might be an early marker of cardiotoxicity induced by antitumor treatment and act as an early predictor of cardiovascular disease-related morbidity and mortality. The impact of thoracic radiotherapy on the parasympathetic and sympathetic nervous systems, however, remains unclear. Therefore, this study aimed to evaluate the short-term effects of thoracic radiotherapy on the autonomic nervous system, using deceleration capacity (DC), acceleration capacity (AC) of heart rate, and heart rate variability (HRV) as assessment tools.MethodsA 5 min electrocardiogram was collected from 58 thoracic cancer patients before and after thoracic radiotherapy for DC, AC, and HRV analysis. HRV parameters employed included the standard deviation of the normal-normal interval (SDNN), root mean square of successive interval differences (RMSSD), low frequency power (LF), high frequency power (HF), total power (TP), and the LF to HF ratio. Some patients also received systemic therapies alongside radiotherapy; thus, patients were subdivided into a radiotherapy-only group (28 cases) and a combined radiotherapy and systemic therapies group (30 cases) for additional subgroup analysis.ResultsThoracic radiotherapy resulted in a significant reduction in DC (8.5 [5.0, 14.2] vs. 5.3 [3.5, 9.4], p = 0.002) and HRV parameters SDNN (9.9 [7.03, 16.0] vs. 8.2 [6.0, 12.4], p = 0.003), RMSSD (9.9 [6.9, 17.5] vs. 7.7 [4.8, 14.3], p = 0.009), LF (29 [10, 135] vs. 24 [15, 50], p = 0.005), HF (35 [12, 101] vs. 16 [9, 46], p = 0.002), TP (74 [41, 273] vs. 50 [33, 118], p

Accelerator driven subcritical reactors have attracted much attention in recent years for their ability to generate energy and transform radioactive waste in a cleaner and safer manner. As an important part of accelerator driven subcritical system (ADS), control system is directly related to the stable and safe operation of the system. Therefore, it is necessary to build a high-precision control system simulation platform that is easy to design and verify. In this paper, a simulation platform coupling Simulink and Locust is developed for the control system design of ADS in China. Based on an explicit thermal coupling strategy (TCS) of interface heat flux and wall temperature, the entire closed-loop system model is established. The simulation platform is divided into two parts according to the coolant type: the first part with lead bismuth eutectic is composed of the shell side of the interface heat exchanger (IHX), reactor, and main pump; the second part with water include the tube side of IHX, air cooler, feedwater pump, and flow network. To verify the effectiveness of the TCS method, the thermohydraulics parameters of once-through steam generator (OTSG) calculated by the coupled model were compared with those calculated by single Locust model under steady and transient conditions.The results show that the two models have good consistency. The coupled platform is able to successfully simulate dynamic processes under different conditions. In addition, simulation verification is carried out under the step change of 10% FP to study its control characteristics. The results show that the control effect of the coupled platform is slightly better than that of single Locust. The control system has a good ability to adjust the ADS system, and extends the functions of traditional Locust without modifying the Locust source code. While ensuring the accuracy of the model, it increases the flexibility of modeling and improves the modeling efficiency, which can provide an important reference for further engineering applications.

Background Intimal hyperplasia contributed by phenotypic switching of vascular smooth muscle cell (VSMC) plays an important role in the pathogenesis of various cardiovascular diseases. MicroRNA-144 (miR-144) is recently reported to be implicated in the development of atherosclerosis. However, the individual role of miR-144 in VSMCs phenotypic modulation and intimal hyperplasia currently still remains unknown. Methods and Results Here we found that miR-144 expression was upregulated in carotid arteries with intimal hyperplasia that subjected to wire injury and the consistent results were obtained with dedifferentiated VSMCs upon platelet-derived growth factor-BB (PDGF-BB) stimulation. Loss-of-function study showed that miR-144 knockdown decreased the ability of VSMC proliferation tested by Brdu and CCK8, and reduced the migrate capability analyzed by Transwell, whereas increased the differentiated SMC marker gene expression examined by RT-PCR. The above results were reversed by miR-144 overexpression. Mechanistically, we have demonstrated that PTEN was the direct target of miR-144 that was responsible for the alleviated effect of miR-144 inhibition on phenotypic switching of VSMCs. Notably, mice injected with miR-144 inhibitor attenuated the formation of neointimal lesions in response to wire injury and maintained the mature SMC marker expression inhibited the proliferation and migration of VSMCs. Conclusion Our research exhibited that miR-144 knockdown attenuated intimal hyperplasia through inhibiting the VSMC phenotypic switching, which was partially mediated by directly targeting to PTEN. Taken together, these evidences suggested that miR-144 may act as a promising therapeutic target for arterial restenosis.

Filter media composed of electrostatically charged nonwovens is the key device in an air purifier. Pleated filters are constructed from a cardboard frame with lattice faces containing a filter media reinforce by an expanded support grid, which have more surface area for trapping contaminants and capture airborne contaminants more effectively than non-pleated air filters. The aim of this work is to investigate the dominant factors on the filtration efficiency and dust holding performance of pleated filter by using a modified numerical model. It is found that geometric parameters of pleated filter play important roles to efficiency of the air purifier based on particle loading and filtration efficiency. The stable structural parameters include bending angle of pleated filter material in the range of 0∼60° and the ratio of bending portion less than 0.5. Lower filling degree and shorter length of pleated filter unit exhibit similar stability of efficiency, indicating that the change of structural parameters has little effects on the filtration performance. The knowledge obtained in this work provides concrete reference for the design of high-performance air-cleaner element.

Coenzyme Q10 (CoQ10) is a powerful antioxidant that is gradually being used in aquafeeds. Here, we examined the influence of oxidized fish oil and CoQ10 supplementation on intestinal microbiota of Micropterus salmoides at different growth stages. Three isonitrogenous and isoenergetic diets were formulated to contain 100% fresh fish oil (FFO), 100% oxidized fish oil (OFO) and OFO + 0.1% CoQ10 (QFO) and were fed to Micropterus salmoides (95 ± 0.60 g) for 70 days. Furthermore, three different growth stages (28-day, 49-day, 70-day) were selected to observe the dynamic changes of intestinal microbiota. The growth performance of fish fed QFO were significantly higher than that of fish fed OFO after a 70-day’s feeding. Intestinal microbial community of Micropterus salmoides was significantly affected by different growth stages more than diets. The abundance of phylum Proteobacteria showed an increasing trend, while the abundance of Firmicutes decreased with increased feeding time. Compared with OFO, diet supplemented with CoQ10 significantly increased the abundance of Firmicutes, and decreased Proteobacteria on the 28- and 70-day of feeding. When fish fed OFO and QFO, Simpson and Shannon indices significantly increased with increased feeding time from 28 to 70 days. Fish fed QFO significantly decreased the value of Bray-Curtis distance than those fed FFO on the 70-day of feeding. Moreover, Bray-Curtis distance showed an increased trend with increased feeding time. Notably, intestinal microbial functional prediction indicated that OFO suppressed amino acid metabolism, while long-term oral administration of CoQ10 could improve amino acid metabolism and detoxification of Micropterus salmoides. This study demonstrated that prolonged application of CoQ10 is needed to produce some beneficial effects to Micropterus salmoides.

The aim of this study was to evaluate the effects of replacing fish meal (FM) or soy protein concentrate (SPC) with wheat gluten on growth performance, feed utilization, and nutrient digestibility and retention in Japanese seabass (Lateolabrax japonicus). Seven isonitrogenous (441–456 g kg−1 crude protein) and isocaloric (21.5–22.0 MJ kg−1 gross energy) diets were produced to replace 0%, 33.3%, 66.7% and 100% of FM or SPC with a mixture of wheat gluten, wheat, and taurine (GWT, 77.5% wheat gluten, 20.5% wheat and 2.0% taurine). The gradual replacement of protein in FM with GWT had no significant effects on feed intake, whole-body composition, and the hepatosomatic and viscerosomatic indices, but resulted in a linear decrease in the weight gain rate, feed efficiency, and retention of nitrogen, energy, and essential amino acids (Arg, His, Ile, Leu, Lys, Met, Phe, Thr, and Val). The apparent digestibility of most essential amino acids (Cys, His, Leu, Lys, and Phe) and total amino acids increased linearly. Replacement protein in SPC with GWT had no significant effects on feed intake, growth, the feed conversion ratio, whole-body composition, and the hepatosomatic index, but resulted in a linear decrease in nitrogen, energy, and Met retention; the digestibility of Cys and Met increased linearly. Overall, wheat gluten is a more effective alternative for replacing protein in SPC than FM.

In recent years, traditional antibiotic efficacy outcomes have rapidly diminished due to the advent of drug resistance, and the dose limitation value has increased due to the severe side effect of globalized healthcare. Therefore, novel strategies are required to resensitize resistant pathogens to antibiotics existing in the field and prevent the emergence of drug resistance. In this study, cationic hyperbranched polylysine (HBPL-6) was synthesized using the one-pot polymerization method. HBPL-6 exhibited excellent non-cytotoxicity and bio-solubility properties. The present study also showed that HBPL-6 altered the outer membrane (OM) integrity of Escherichia coli O157:H7, Salmonella typhimurium, and Pseudomonas aeruginosa PAO1 by improving their permeability levels. When administered at a safe dosage, HBPL-6 enhanced the accumulation of rifampicin (RIF) and erythromycin (ERY) in bacteria to restore the efficacy of the antibiotics used. Moreover, the combination of HBPL-6 with colistin (COL) reduced the antibiotic dosage, which was helpful in preventing further drug-resistance outcomes. Therefore, this research provides a new strategy for reducing the dosage of drugs used to combat Gram-negative (G−) bacteria through their synergistic effects.

A two-channel, time–wavelength interleaved photonic analog-to-digital converter (PADC) system with a sampling rate of 10.4 GSa/s was established, and a concise method for measuring and data correcting the channel sampling timing walk-off of PADCs for signal recovery was proposed. The measurements show that for the two RF signals of f1 = 100 MHz and f2 = 200 MHz, the channel sampling timing walk-off was 12 sampling periods, which results in an ENOB = −0.1051 bits for the 100 MHz directly synthesized signal, while the ENOB improved up to 4.0136 bits using shift synthesis. In addition, the peak limit method (PLM) and normalization processing were introduced to reduce the impacts of signal peak jitter and power inconsistency between two channels, which further improve the ENOB of the 100 MHz signal up to 4.5668 bits. All signals were analyzed and discussed in both time and frequency domains. The 21.1 GHz signal was also collected and converted using the established two-channel PADC system with the data correction method, combining the PLM, normalization, and shift synthesis, showing that the ENOB increased from the initial −0.9181 to 4.1913 bits, which demonstrates that our method can be effectively used for signal recovery in channel-interleaved PADCs.

In aquatic ecosystems, the interaction between heavy metals and dissolved organic carbon (DOC) plays a pivotal role in modifying the bioavailability of these metals. This study, employing a toxicokinetic–toxicodynamic model, delves into the interactive effects of humic acid (HA), a significant component of DOC, on the bioaccumulation and toxicity of copper (Cu) in the estuarine economic bivalve Sinonovacula constricta. Utilizing the stable isotope 65Cu as a tracer, we evaluated Cu uptake in S. constricta under varied DOC concentrations in a controlled laboratory setting. Our findings reveal that at DOC concentrations below 3.05 mg L−1, the bioavailability of Cu is reduced due to shifts in the speciation distribution of Cu, resulting in decreased bioaccumulation within S. constricta. Conversely, at DOC levels exceeding 3.05 mg L−1, the formation of colloidal Cu–HA complexes allows its entry into the bivalves’ digestive system. Moreover, toxicity assays demonstrate an increase in S. constricta survival rates with higher DOC concentrations, suggesting a protective effect of DOC against Cu toxicity. The integration of accumulation and toxicity data infers that Cu–HA complexes, when ingested via the digestive tract, exhibit lower toxicity compared to Cu directly assimilated from the water phase. These findings emphasize the need to consider environmental DOC levels in assessing Cu pollution risks and provide insights for managing heavy metal toxicity in estuarine aquaculture.

Shin et al. report the molecular mechanics of membrane budding: actin and dynamin pull membrane inward to form a Λ-shape profile; dynamin helices convert Λ- to Ω-shape by constricting Λ’s base, and then constrict Ω-profile’s pore to form a vesicle.

BackgroundPrevious studies have shown that the predictive value of traditional linear (time domain and frequency domain) heart rate variability (HRV) for the survival of patients with advanced non-small cell lung cancer (NSCLC) is controversial. Nonlinear methods, based on the concept of complexity, have been used to evaluate HRV, providing a new means to reveal the physiological and pathological changes in HRV. This study aimed to assess the association between heartbeat complexity and overall survival in patients with advanced NSCLC.MethodsThis study included 78 patients with advanced NSCLC (mean age: 62.0 ± 9.3 years). A 5-min resting electrocardiogram of advanced NSCLC patients was collected to analyze the following HRV parameters: time domain indicators, i.e., standard deviation of the normal-normal intervals (SDNN) and root mean square of successive interval differences (RMSSD); frequency domain indicators, i.e., total power (TP), low frequency power (LF), high frequency power (HF), and the ratio of LF to HF (LF/HF); nonlinear HRV indicators characterizing heartbeat complexity, i.e., approximate entropy (ApEn), sample entropy (SampEn), and recurrence quantification analysis (RQA) indexes: mean diagonal line length (Lmean), maximal diagonal line length (Lmax), recurrence rate (REC), determinism (DET), and shannon entropy (ShanEn).ResultsUnivariate analysis revealed that the linear frequency domain parameter HF and nonlinear RQA parameters Lmax, REC, and DET were significantly correlated with the survival of advanced NSCLC patients (all p

Ligusticum chuanxiong Hort. as an important Chinese medicinal herb clinically used as anti-inflammatory, antioxidant, and hepatoprotective agents, is widely planted in China. However, related studies on L. chuanxiong’s distribution and significant environmental factors that affect its growth are insufficient. Based on climatic, topographic and soil factors, this study predicted current and future distributions of L. chuanxiong and analyzed the distribution transformation under different scenarios. Moreover, the most important environmental factors for modeling were explored using maximum entropy models, chemical analysis and molecular analysis. Results suggested that the predicted distribution of L. chuanxiong was wider than previously reported. Among these environmental variables, climate factors, especially the minimum temperature of the coldest month (Bio6, 46.7%) and solar radiation (SRAD, 43.4%) contributed more than others to L. chuanxiong’s distribution with optimum values of 0–1.5 °C and 5000–11,000 kJ/m2 per day. Total and highly suitable areas respectively increased by 26,788–943,820 km2 and 34,757–340,417 km2 in the future (2061–2080, 2081–2100). The distribution centers of suitable zones were predicted to migrate north in the future, and the migration distance was 135.74–479.77 km from current center. Results of chemical content determination suggested that L. chuanxiong should be cultivated in high-suitable places to improve medicinal quality by evaluating contents of ferulic acids and Z-ligustilide. Correlation analysis suggested that both chemical contents and gene expression levels decreased with decreasing habitat suitability, suggesting a strong link between environments, chemical constituents, and gene expression. These findings improve the comprehension of the effects of environments on the distribution patterns of L. chuanxiong, as well the relation between environmental suitability and medicinal quality. These findings provide a useful foundation for the planting, cultivation and conservation of L. chuanxiong.

In order to study the current situation of the anxiety of college students in the post-pandemic era and the effect of physical exercise on anxiety, this study explores the influence of social support and proactive personality as mediating variables on the anxiety of college students from the perspective of physical exercise. Firstly, anxiety symptoms and anxious emotions are defined. Secondly, a questionnaire survey is conducted for a well-known university in a certain city, and different questionnaire scales are developed from the physical exercise, anxiety, social support, and proactive personality assessment of college students. Finally, the results of the survey are statistically analyzed to explore the relieving effect of physical exercise on anxiety. The results reveal that there is a significant gender difference in the level of physical exercise, and the amount of physical exercise of the male students is generally higher than that of female students. In addition, the intensity, time, and frequency of exercise of male students are more than that of female students, but there is no obvious difference between them and whether they were only children. Physical exercise habits, social support, proactive personality traits, and anxiety of college students have a significant correlation. Through the analysis of the chain mediation effect, Ind2 (0.0140) is the largest coefficient among the three paths, indicating that the path of influencing social support through physical exercise habits, followed by affecting proactive personality traits, and then impacting anxiety has the strongest explanatory force. According to the results, strategies to relieve the anxiety of college students are given. This study can provide a reference for the research on the methods to alleviate their anxiety under the influence of the epidemic.

The effects of optical sampling pulse power, RF power, and electronic back-end bandwidth on the performance of time- and wavelength-interleaved photonic analog-to-digital converter (PADC) with eight-channel 41.6 GHz pulses have been experimentally investigated in detail. The effective number of bits (ENOB) and peak-to-peak voltage (Vpp) of converted 10.6 GHz electrical signals were used to characterize the effects. For the 1550.116 nm channel with 5.2 G samples per second, an average pulse power of 0 to −10 dBm input to the photoelectric detector (PD) has been tested. The Vpp increased with increasing pulse power. And the ENOB for pulse power −9~−3 dBm was almost the same and all were greater than four. Meanwhile, the ENOB decreased either when the pulse power was more than −2 dBm due to the saturation of PD or when the pulse power was less than −10 dBm due to the non-ignorable noise relative to the converted weak signal. In addition, RF powers of −10~15 dBm were loaded into the Mach–Zehnder modulator (MZM). The Vpp increased with the increase in RF power, and the ENOB also showed an increasing trend. However, higher RF power can saturate the PD and induce greater nonlinearity in MZM, leading to a decrease in ENOB, while lower RF power will convert weak electrical signals with more noise, also resulting in lower ENOB. In addition, the back-end bandwidths of 0.2~8 GHz were studied in the experiments. The Vpp decreased as the back-end bandwidth decreased from 8 to 3 GHz, and remained nearly constant for the bandwidth between the Nyquist bandwidth and the subsampled RF signal frequency. The ENOB was almost the same and all greater than four for a bandwidth from 3 to 8 GHz, and gradually increased up to 6.5 as the back-end bandwidth decreased from the Nyquist bandwidth to 0.25 GHz. A bandwidth slightly larger than the Nyquist bandwidth was recommended for low costs and without compromising performance. In our experiment, the −3 to −5 dBm average pulse power, about 10 dBm RF power, and 3 GHz back-end bandwidth were recommended to accomplish both a high ENOB more than four and large Vpp. Our research provides a solution for selecting optical sampling pulse power, RF power, and electronic back-end bandwidth to achieve low-cost and high-performance PADC.

Timely and accurate flame detection is a very important and practical technology for preventing the occurrence of fire accidents effectively. However, the current methods of flame detection are still faced with many challenges in video surveillance scenarios due to issues such as varying flame shapes, imbalanced samples, and interference from flame-like objects. In this work, a real-time flame detection method based on deformable object detection and time sequence analysis is proposed to address these issues. Firstly, based on the existing single-stage object detection network YOLOv5s, the network structure is improved by introducing deformable convolution to enhance the feature extraction ability for irregularly shaped flames. Secondly, the loss function is improved by using Focal Loss as the classification loss function to solve the problems of the imbalance of positive (flames) and negative (background) samples, as well as the imbalance of easy and hard samples, and by using EIOU Loss as the regression loss function to solve the problems of a slow convergence speed and inaccurate regression position in network training. Finally, a time sequence analysis strategy is adopted to comprehensively analyze the flame detection results of the current frame and historical frames in the surveillance video, alleviating false alarms caused by flame shape changes, flame occlusion, and flame-like interference. The experimental results indicate that the average precision (AP) and the F-Measure index of flame detection using the proposed method reach 93.0% and 89.6%, respectively, both of which are superior to the compared methods, and the detection speed is 24–26 FPS, meeting the real-time requirements of video flame detection.

Particle swarm optimization (PSO) has been considered as one of the main swarm intelligence algorithms for solving single-objective optimization problem. How to update the velocities and positions of a swarm of particles is key to its optimization performance. In this paper, we propose to use the moving average of the local best positions visited so far as a key information to update the velocities and positions. Further, a central learning strategy is proposed in which the center of the local best positions is computed and used to update the global best position. Combining these two strategies with the updating formulas which are inspired by the free electron model in metal conductors placed in an external electric field, we name the proposed PSO algorithm as PSO with moving average and central learning strategies (dubbed as MAPSO). We test the performance of MAPSO on the CEC 2017 test problems with 10 and 30 dimensions. Experimental results show that MAPSO significantly outperforms some well-known PSOs in general. We then apply MAPSO on a very challenging real-world problem, i.e. the yield curve estimation problem, in macroeconomics. Our experimental study on the yield curve estimation problem with Shanghai interbank offered rates shows that MAPSO can effectively solve the problem and achieve the state-of-the-art performance.

Background: Previous studies have shown that heart rate variability (HRV) analysis is a sensitive indicator of chemotherapy-induced cardiotoxicity. However, most studies to date have observed long-term effects using long-term analyses. The main purpose of this study was to evaluate the acute effect of chemotherapy on the cardiac autonomic nervous system (ANS) in patients with cervical cancer (CC) by examining short-term HRV.Methods: Fifty patients with CC admitted to the Department of Gynecology and Oncology of the First Affiliated Hospital of Bengbu Medical College were enrolled in the study. Based on their chemotherapy regimens, the patients were divided into a DC group (docetaxel + carboplatin) and a TC group (paclitaxel + carboplatin). A 5-min resting electrocardiogram (ECG) was collected before and the day after chemotherapy: the time domain (standard deviation of normal-to-normal intervals (SDNN) and root mean square of successive differences (RMSSD)) and frequency domain (low-frequency power (LF), high-frequency power (HF), and (LF/HF)) parameters were analyzed, and the differences before and after chemotherapy were compared.Results: The results showed that SDNN, RMSSD and HF were significantly higher in the DC and TC groups after chemotherapy than before (p < 0.05, Cohen’s d > 0.5). In addition, LF was significantly higher after TC than before chemotherapy (p < 0.05, Cohen’s d > 0.3), and LF/HF was significantly lower after DC than before chemotherapy (p < 0.05, Cohen’s d > 0.5).Conclusion: Chemotherapy combining taxane and carboplatin can increase the HRV of CC patients in the short term, and HRV may be a sensitive tool for the early detection of chemotherapy-induced cardiac ANS perturbations.