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Abstract Background Glechoma longituba, recognized as a medicinal plant, provides valuable pharmaceutical raw materials for treating various diseases. Saline-alkali stress may effectively enhance the medicinal quality of G. longituba by promoting the synthesis of secondary metabolites. To investigate the changes in the primary medicinal components of G. longituba under saline-alkali stress and improve the quality of medicinal materials, Na2CO3 was applied to induce short-term stress under different conditions and the biomass, physiologically active substances and primary medicinal components of G. longituba were measured in this study. Results Under alkaline salt stress, the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), and ascorbate peroxidase (APX) were elevated in G. longituba, accompanied by increased accumulation of proline (Pro) and malondialdehyde (MDA). Furthermore, analysis of the medicinal constituents revealed that G. longituba produced the highest levels of soluble sugars, flavonoids, ursolic acid, and oleanolic acid under 0.6% Na2CO3 stress for 48 h, 0.2% Na2CO3 stress for 72 h, 0.4% Na2CO3 stress for 12 h, and 0.4% Na2CO3 stress for 8 h, respectively. Conclusions Short-term Na2CO3 stress enhances the synthesis of medicinal components in G. longituba. By manipulating stress conditions, the production of various medicinal substances could be optimized. This approach may serve as a basis for the targeted cultivation of G. longituba, offering potential applications in the treatment of diverse diseases.

Abstract The electrical conductivity of the earth’s mantle can provide important information about geodynamic phenomena. East Asia is associated with complex tectonics and geodynamic processes. Hence, it is necessary to better understand the deep structure beneath East Asia. In this study, geomagnetic data obtained from East Asian observatories are employed to image the conductivity structure of the mantle at depths ranging from 410 to 900 km. First, the data are processed using the modified bounded influence remote reference processing (BIRRP) method and the ratio method is used to correct for the ocean effect. Thereafter, the stable C-response curves at the 27 observatories are estimated, and 1D electrical conductivity models for these observatories are established using the L-BFGS method. The conductivity-depth profiles reveal a heterogeneous distribution of the electrical conductivity beneath East Asia. The mantle transition zone (MTZ) beneath East China and Japan is found to be more conductive, whereas the MTZ beneath central and southern regions of China is more resistive. In East China, the dehydration of the stagnant Pacific slab may lead to an increase in the conductivity of the mantle minerals. There is also the possibility of upwelling of the thermal material from the lower mantle beneath the Japanese Island arc. In Northwest China, there exists a large high-conductive body beneath the Tarim area, which could indicate an upwelling of the Tarim mantle plume. Our results provide insights into the deep structure of the earth at the mantle scale.

Abstract This study assesses the efficacy of bilateral mesh sacrospinous ligament suspension (MSSLS) compared to laparoscopic sacrocolpopexy (LSC) in patients with uterine prolapse. Ninety-eight patients with uterine prolapse were evaluated at our hospital from January 2021 to January 2023. Patients were equally divided into two groups: the study group (undergoing MSSLS) and the control group (undergoing LSC) using a random number table. Various parameters including operation time, bleeding volume, indwelling catheter time, exhaust time, hospital stay, pelvic organ prolapse stage, postoperative recurrence rate, pain severity, quality of life, pelvic floor function, impact on sexual life, complications, and recurrence rate were recorded. The study group showed significant reductions in operation time, bleeding volume, indwelling catheter time, exhaust time, and hospital stay compared to the control group (P 0.05), but six months postoperatively, these indexes were significantly lower in the study group (P 0.05), but was significantly lower in the study group six months postoperatively (P 0.05). All patients were followed up for 12–14 months, with an average follow-up time of (13.02 ± 1.36) months. The incidence of complications was significantly lower in the study group (P 0.05). MSSLS emerges as a safe and efficacious treatment for uterine prolapse, notably reducing both complications and recurrence rates, rendering it suitable for broad clinical application.

Ovarian cancer is a common cancer for females, and the incidence and mortality rates are on the rise. Many treatment strategies have been developed for ovarian cancer, including chemotherapy and immunotherapy, but they are often ineffective and prone to drug resistance. Protein ubiquitination is an important class of post-translation modifications that have been found to be associated with various human diseases and cancer development. Recent studies have revealed that protein ubiquitination is involved in the progression of ovarian cancer and plays an important role in the tumor immune process. Moreover, the combination of ubiquitinase/deubiquitinase inhibitors and cancer immunotherapy approaches can effectively reduce treatment resistance and improve treatment efficacy, which provides new ideas for cancer treatment. Herein, we review the role of protein ubiquitination in relation to ovarian cancer immunotherapy and recent advances in the use of ubiquitinase/deubiquitinase inhibitors in combination with cancer immunotherapy.

Accumulating studies have highlighted the great potential of postbiotics in alleviating diseases and protecting host health. Compared with traditional functional foods (such as probiotics and prebiotics), postbiotics have the advantages of a single composition, high physiological activity, long shelf life, easy absorption, and high targeting, etc. The development of postbiotics has led to a wide range of potential applications in functional food and drug development. However, the lack of clinical trial data, mechanism analyses, safety evaluations, and effective regulatory frameworks has limited the application of postbiotic products. This review describes the definition, classification, sources, and preparation methods of postbiotics, the progress and mechanism of preclinical and clinical research in improving host diseases, and their application in food. Strengthen understanding of the recognition and development of related products to lay a theoretical foundation.

Summary: Selection of fruits with enhanced health benefits and superior flavor is an important aspect of peach breeding. Understanding the genetic interplay between appearance and flavor chemicals remains a major challenge. We identify the most important volatiles contributing to consumer preferences for peach, thus establishing priorities for improving flavor quality. We quantify volatiles of a peach population consisting of 184 accessions and demonstrate major reductions in the important flavor volatiles linalool and Z-3-hexenyl acetate in red-fleshed accessions. We identify 474 functional gene regulatory networks (GRNs), among which GRN05 plays a crucial role in controlling both red flesh and volatile content through the NAM/ATAF1/2/CUC (NAC) transcription factor PpBL. Overexpressing PpBL results in reduced expression of PpNAC1, a positive regulator for Z-3-hexenyl acetate and linalool synthesis. Additionally, we identify haplotypes for three tandem PpAATs that are significantly correlated with reduced gene expression and ester content. We develop genetic resources for improvement of fruit quality.

Chronic inflammation is a common foundation for the development of many non-communicable diseases, particularly diabetes, atherosclerosis, and tumors. The activation of the axis involving Advanced Glycation End products (AGEs) and their receptor RAGE is a key promotive factor in the chronic inflammation process, influencing the pathological progression of these diseases. The accumulation of AGEs in the body results from an increase in glycation reactions and oxidative stress, especially pronounced in individuals with diabetes. By binding to RAGE, AGEs activate signaling pathways such as NF-κB, promoting the release of inflammatory factors, exacerbating cell damage and inflammation, and further advancing the formation of atherosclerotic plaques and tumor development. This review will delve into the molecular mechanisms by which the AGEs-RAGE axis activates chronic inflammation in the aforementioned diseases, as well as strategies to inhibit the AGEs-RAGE axis, aiming to slow or halt the progression of chronic inflammation and related diseases. This includes the development of AGEs inhibitors, RAGE antagonists, and interventions targeting upstream and downstream signaling pathways. Additionally, the early detection of AGEs levels and RAGE expression as biomarkers provides new avenues for the prevention and treatment of diabetes, atherosclerosis, and tumors.

Objective: Type 2 diabetes mellitus (T2DM) is a common chronic metabolic disease. Peroxisome proliferator-activated receptors (PPARs) play crucial roles in regulating glucolipid metabolism. Previous studies showed that E17241 could ameliorate atherosclerosis and lower fasting blood glucose levels in ApoE−/− mice. In this work, we investigated the role of E17241 in glycolipid metabolism in diabetic KKAy mice. Approach and results: We confirmed that E17241 is a powerful pan-PPAR agonist with a potent agonistic activity on PPARγ, a high activity on PPARα, and a moderate activity on PPARδ. E17241 also significantly increased the protein expression of ATP-binding cassette transporter 1 (ABCA1), a crucial downstream target gene for PPARs. E17241 clearly lowered plasma glucose levels, improved OGTT and ITT, decreased islet cholesterol content, improved β-cell function, and promoted insulin secretion in KKAy mice. Moreover, E17241 could significantly lower plasma total cholesterol and triglyceride levels, reduce liver lipid deposition, and improve the adipocyte hypertrophy and the inflammatory response in epididymal white adipose tissue. Further mechanistic studies indicated that E17241 boosts cholesterol efflux and insulin secretion in an ABCA1 dependent manner. RNA-seq and qRT-PCR analysis demonstrated that E17241 induced different expression of PPAR target genes in liver and adipose tissue differently from the PPARγ agonist rosiglitazone. In addition, E17241 treatment was also demonstrated to have an exhilarating cardiorenal benefits. Conclusions: Our results demonstrate that E17241 regulates glucolipid metabolism in KKAy diabetic mice while having cardiorenal benefits without inducing weight gain. It is a promising drug candidate for the treatment of T2DM.

Abstract Background We analyzed the clinical characteristics of children with plastic bronchitis (PB) caused by Mycoplasma pneumoniae (MP) and explored its risk factors. Methods We prospectively analyzed clinical data of children with MP pneumonia (MPP) treated with fiberoptic bronchoscopy (FB). Patients were classified into a PB and non-PB group. General information, clinical manifestations, laboratory tests, results of computed tomography scan, and FB findings were compared between groups. We conducted statistical analysis of risk factors for developing PB. Results Of 1169 children who had MPP and were treated with FB, 133 and 1036 were in the PB and non-PB groups, respectively. There were no significant differences in sex, age, and incident season between groups (P > 0.05). The number of children in the PB group decreased during the COVID-19 pandemic. Compared with children in the non-PB group, those in the PB group had longer duration of hospitalization, increased levels of neutrophil (N), C-reactive protein (CRP), procalcitonin (PCT), D-dimer, lactate dehydrogenase (LDH), alanine transaminase (ALT) and aspartate transaminase (AST); lower levels of lymphocyte (L) and platelet (PLT); and higher incidence of lack of appetite, decreased breath sounds, single lobar infiltrate, pleural effusion, pericardial effusion, mucosal erosion and/or necrosis, and bronchial embolization. L levels and pleural effusion were identified as risk factors in multivariate logistic regression. Conclusions Children with PB caused by MPP had a strong and local inflammatory response. L levels and pleural effusion were independent risk factors of PB with MPP in children. Our findings will help clinicians identify potential PB in pediatric patients for early and effective intervention.

Abstract Objective Acute nonvariceal upper gastrointestinal bleeding (ANVUGIB) is a common clinical emergency. Transcatheter arterial embolization (TAE) is usually used to locate the bleeding site and provide interventional embolization. During TAE, there is a low positive rate of angiography, and localization of the culprit vessel is difficult. The purpose of this study was to demonstrate the role of preplaced metal clips in TAE for ANVUGIB patients. Materials and methods Patients with ANVUGIB in whom bleeding sites were identified endoscopically and treated with TAE from January 1st, 2005 to July 1st, 2021 were retrospectively included. According to the presence or absence of preplaced metal clips, they were divided into two groups. The main outcome measurements included the clinical success rate and rebleeding rate. Secondary outcome measurements included the mortality rate and the need for surgery. Predictors of the clinical success rate were assessed with univariate analysis and multivariate analysis. Results A total of 102 patients were included in this study, and all of them had undergone arterial embolization. There were 73 cases in the group with metal clips and 29 cases in the group without metal clips with consistent baseline information. The group with metal clips had a higher clinical success rate (82.2% vs. 45.0%, P

Let s, t be two positive integers and k be an algebraically closed field with char (k)∤st. We show that the Drinfeld double D(⋀st,t*cop) of generalized Taft–Hopf algebra ⋀st,t*cop has ribbon elements if and only if t is odd. Moreover, if s is even and t is odd, then D(⋀st,t*cop) has two ribbon elements, and if both s and t are odd, then D(⋀st,t*cop) has only one ribbon element. Finally, we compute explicitly all ribbon elements of D(⋀st,t*cop).

Abstract Accumulating studies have shown the effects of gut microbiota management tools in improving depression. We conducted a meta-analysis to evaluate the effects of prebiotics, probiotics, and synbiotics on patients with depression. We searched six databases up to July 2022. In total, 13 randomized controlled trials (RCTs) with 786 participants were included. The overall results demonstrated that patients who received prebiotics, probiotics or synbiotics had significantly improved symptoms of depression compared with those in the placebo group. However, subgroup analysis only confirmed the significant antidepressant effects of agents that contained probiotics. In addition, patients with mild or moderate depression could both benefit from the treatment. Studies with a lower proportion of females reported stronger effects for alleviating depressive symptoms. In conclusion, agents that manipulate gut microbiota might improve mild-to-moderate depression. It is necessary to further investigate the benefits of prebiotic, probiotic and synbiotic treatments relative to antidepressants and follow up with individuals over a longer time before these therapies are implemented in clinical practice.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases. Silencing information regulator 1 (SIRT1) was demonstrated to modulate cholesterol and lipid metabolism in NAFLD. Here, a novel SIRT1 activator, E1231, was studied for its potential improvement effects on NAFLD. C57BL/6J mice were fed a high-fat and high-cholesterol diet (HFHC) for 40 weeks to create a NAFLD mouse model, and E1231 was administered by oral gavage (50 mg/kg body weight, once/day) for 4 weeks. Liver-related plasma biochemistry parameter tests, Oil Red O staining, and hematoxylin-eosin staining results showed that E1231 treatment ameliorated plasma dyslipidemia, plasma marker levels of liver damage (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)), liver total cholesterol (TC) and triglycerides (TG) contents, and obviously decreased hepatic steatosis score and NAFLD Activity Score (NAS) in the NAFLD mouse model. Western blot results showed that E1231 treatment significantly regulated lipid-metabolism-related protein expression. In particular, E1231 treatment increased SIRT1, PGC-1α, and p-AMPKα protein expression but decreased ACC and SCD-1 protein expression. Additionally, in vitro studies demonstrated that E1231 inhibited lipid accumulation and improved mitochondrial function in free-fatty-acid-challenged hepatocytes, and required SIRT1 activation. In conclusion, this study illustrated that the SIRT1 activator E1231 alleviated HFHC-induced NAFLD development and improved liver injury by regulating the SIRT1-AMPKα pathway, and might be a promising candidate compound for NAFLD treatment.

Category: Hindfoot; Midfoot/Forefoot Introduction/Purpose: When AP, lateral, and hindfoot views weight bearing XR's were taken, patients were frequently asked to stand on the foot being examined with the other foot lifted off the floor. However, we have found that alignments of the hind and midfoot during unilateral standing are different from those when bearing weight on both feet. This study compared the kinematics and plantar pressures between unilateral and bilateral standing positions in a group of asymptomatic volunteers. Methods: Ten participants (20 feet) without symptoms, previous trauma and surgical history in both lower limbs were included. Each participant first stood comfortably on both feet, then lifted the non-examined foot off the floor. Each person switched between the above two positions three times. Kinematic data was collected using an eight-camera Optitrack 3D motion capture system to reflect changes in alignments of the ankle, subtalar, and midtarsal joints. Plantar pressure distribution was assessed using a pressure platform. Paired t-tests were used to compare the metrics between the two standing positions, with statistical significance level set at P < 0.05. Results: From bilateral to unilateral weightbearing, 14 out of 21 kinematic angular parameters showed medium to high level of statistical significance (p=0.001-0.046) reflecting differences in the relative positions of the ankle, subtalar, and midtarsal joints in the two weightbearing positions resulting from pronation of the hindfoot and midfoot; the average plantar pressure change underneath the hallux (0.1616N), toes 2-5 (0.0907N), metatarsals 2-4 (0.2481N, 0.3204N, 0.2649N), midfoot (0.1794N), medial and lateral heel (0.259N, 0.246N) all showed statistically significant increase. There was a significantly higher plantar pressure increase on the medial than the lateral side of the feet. This corresponded to both the kinematic changes, and our findings in another study investigating the alignment change between the positions radiographically. Conclusion: The hindfoot and midfoot are more pronated in unilateral weightbearing than in bilateral weightbearing which may mask the severity of the deformity in a flexible cavovarus foot but increase that in a flexible flatfoot. Modification of the traditionally used unilateral weightbearing position in obtaining clinical radiographs should be considered. Bilateral WBCT scans may be a better alternative, taking advantage of allowing both feet to bearing weight naturally without concerning about one foot blocking the other during the radiographic imaging.

Abstract Lattice structures created using additive manufacturing technology inevitably produce inherent defects that seriously affect their mechanical properties. Predicting and analysing the effect of defects on the maximum stress is very important for improving the lattice structure design and process. This study mainly used the finite element method to calculate the lattice structure constitutive equation. The increase in defect type and quantity leads to difficulty in modelling and reduces calculation accuracy. We established a data-driven extreme gradient enhancement (XGBoost) with hyperparameter optimization to predict the maximum stress of the lattice structure in additive manufacturing. We used four types of defect characteristics that affect the mechanical properties—the number of layers, thick-dominated struts (oversize), thin-dominated struts (undersizing), and bend-dominated struts (waviness)—as the input parameters of the model. The hyperparameters of the basic XGBoost model were optimised according to the diversity of the inherent defect characteristics of the lattice structure, while the parameters selected by experience were replaced using the Gaussian process method in Bayesian optimization to improve the model’s generalisation ability. The prediction datasets included the type and number of defects obtained via computer tomography and the calculation results of the finite element model with the corresponding defects implanted. The root mean square error and R-squared error of the maximum stress prediction were 17.40 and 0.82, respectively, indicating the effectiveness of the model proposed in this paper. Furthermore, we discussed the influence of the four types of defects on the maximum stress, among which the thick strut defect had the greatest influence.

Abstract Aims To examine how metabolic status is associated with microvascular phenotype and to identify variables associated with vascular remodeling after bariatric surgery, using noninvasive optical coherence tomography angiography (OCTA). Methods The study included 136 obese subjects scheduled for bariatric surgery and 52 normal‐weight controls. Patients with obesity were divided into metabolically healthy obesity (MHO) and metabolic syndrome (MetS) groups according to the diagnosis criteria of the Chinese Diabetes Society. Retinal microvascular parameters were measured by OCTA, including superficial capillary plexus (SCP) and deep capillary plexus (DCP) vessel densities. Follow‐ups were performed at the baseline and 6 months after bariatric surgery. Results Fovea SCP, average DCP, fovea DCP, parafovea DCP, and perifovea DCP vessel densities were significantly lower in the MetS group, compared to controls (19.91% vs. 22.49%, 51.60% vs. 54.20%, 36.64% vs. 39.14%, 56.24% vs. 57.65% and 52.59% vs. 55.58%, respectively, all p

Plant plasma membrane H+-ATPase is a transport protein that is generally located on the plasma membrane and generates energy by hydrolyzing adenosine triphosphate (ATP) to pump hydrogen ions (H+) in the cytoplasm out of the cell against a concentration gradient. The plasma membrane H+-ATPases in plants are encoded by a multigene family and potentially play a fundamental role in regulating plant responses to various abiotic stresses, thus contributing to plant adaptation under adverse conditions. To understand the characteristics of the plasma membrane H+-ATPase family in peach (Prunus persica), this study analyzed the plasma membrane H+-ATPase family genes in peach. The results showed that there were 27 members of the plasma membrane H+-ATPase family in peach with amino acid sequences ranging from 943 to 1327. Subcellular localization showed that 23 of the 27 members were located on the cell membrane, and the phylogenetic tree analysis indicated that peach plasma membrane H+-ATPase members were divided into five groups. There were four genes with tandem repeat relationships, and six plasma membrane H+-ATPase genes were differentially expressed after 5 days of flooding and under non-flooding conditions based on the RNA-seq and RT-qPCR analyses. This study also investigated the characteristics and possible functions of the plasma membrane H+-ATPase family members in peach. The results provide theoretical support for further studies on their biological functions in peach.

Flexible job shops motivated by small batches and multiple orders require the collaboration of machines and automated guided vehicles (AGVs) scheduling to boost shop floor flexibility and productivity. The joint scheduling of machines and AGVs can better achieve global optimization. However, joint scheduling requires two NP hard problems to be solved simultaneously. Therefore, this paper employs a multi-AGV flexible job shop scheduling problem (MA-FJSP) with an effective hybrid algorithm. First of all, a model is established with the objectives of minimizing the makespan, the total AGV running time and the total machine load. To solve the MA-FJSP, high-quality initialization methods and improved elite strategies are designed to improve global convergence in the proposed algorithm. In addition, a problem-knowledge-based neighborhood search is integrated to improve its exploitation capability. At last, a series of comparative experimental studies were performed to exam the effectiveness of the improved algorithm. The results demonstrate that the solutions gained by the proposed algorithm perform well in respect of convergence, diversity and distribution.

Abstract Background Inhaled NO is a selective pulmonary vasodilator proven to be therapeutic for patients with pulmonary artery hypertension (PAH). The most common NO delivery system in clinical practice is cylinder-based, but unfortunately limited by its high costs, complicated delivery, and the requirement of an extensive supply chain, leaving vast unmet medical needs globally. Methods To address the need for rapid, affordable, and safe production of nitric oxide (NO) for in-home inhalation therapy in patients with PAH. We developed a novel portable device to derive NO from a nitrite complex solution with a copper(II)-ligand catalyst, and further examined its effectiveness in a porcine model of PAH. This model was established by using female Bama miniature pig and induced by monocrotaline (MCT) administration. Results This generator could rapidly and safely produce therapeutic NO at concentrations ranging from 0 to 100 parts per million (ppm) with the least disproportionated nitrogen dioxide (NO2) and byproducts. It could effectively alleviate pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR) in piglets with PAH, without causing major physiologic disruptions. Conclusions Our electrochemical NO generator is able to produce the desired NO doses for pulmonary vasodilation in a safe and sustainable way, with low costs, which paves the way for its subsequent clinical trials in the patient with PAH and other common cardiopulmonary conditions with a high disease burden around the world.

ABSTRACT The two-component system (TCS) PhoPQ has been demonstrated to be crucial for the formation of resistance to quinolones and cephalosporins in Salmonella Enteritidis (S. Enteritidis). However, the mechanism underlying PhoPQ-mediated antibiotic resistance formation remains poorly understood. Here, it was shown that PhoP transcriptionally regulated an assortment of genes associated with envelope homeostasis, the osmotic stress response, and the redox balance to confer resistance to quinolones and cephalosporins in S. Enteritidis. Specifically, cells lacking the PhoP regulator, under nalidixic acid and ceftazidime stress, bore a severely compromised membrane on the aspects of integrity, fluidity, and permeability, with deficiency to withstand osmolarity stress, an increased accumulation of intracellular reactive oxygen species, and dysregulated redox homeostasis, which are unfavorable for bacterial survival. The phosphorylated PhoP elicited transcriptional alterations of resistance-associated genes, including the outer membrane porin ompF and the aconitate hydratase acnA, by directly binding to their promoters, leading to a limited influx of antibiotics and a well-maintained intracellular metabolism. Importantly, it was demonstrated that the cavity of the PhoQ sensor domain bound to and sensed quinolones/cephalosporins via the crucial surrounding residues, as their mutations abrogated the binding and PhoQ autophosphorylation. This recognition mode promoted signal transduction that activated PhoP, thereby modulating the transcription of downstream genes to accommodate cells to antibiotic stress. These findings have revealed how bacteria employ a specific TCS to sense antibiotics and combat them, suggesting PhoPQ as a potential drug target with which to surmount S. Enteritidis. IMPORTANCE The prevalence of quinolone and cephalosporin-resistant S. Enteritidis is of increasing clinical concern. Thus, it is imperative to identify novel therapeutic targets with which to treat S. Enteritidis-associated infections. The PhoPQ two-component system is conserved across a variety of Gram-negative pathogens, by which bacteria adapt to a range of environmental stimuli. Our earlier work has demonstrated the importance of PhoPQ in the resistance formation in S. Enteritidis to quinolones and cephalosporins. In the current work, we identified a global profile of genes that are regulated by PhoP under antibiotic stresses, with a focus on how PhoP regulated downstream genes, either positively or negatively. Additionally, we established that PhoQ sensed quinolones and cephalosporins in a manner of directly binding to them. These identified genes and pathways that are mediated by PhoPQ represent promising targets for the development of a drug potentiator with which to neutralize antibiotic resistance in S. Enteritidis.

Cervical spondylotic myelopathy (CSM) is the main cause of adult spinal cord dysfunction, mostly appearing in middle-aged and elderly patients. Currently, the diagnosis of this condition depends mainly on the available imaging tools such as X-ray, computed tomography and magnetic resonance imaging (MRI), of which MRI is the gold standard for clinical diagnosis. However, MRI data cannot clearly demonstrate the dynamic characteristics of CSM, and the overall process is far from cost-efficient. Therefore, this study proposes a new method using multiple gait parameters and shallow classifiers to dynamically detect the occurrence of CSM. In the present study, 45 patients with CSM and 45 age-matched asymptomatic healthy controls (HCs) were recruited, and a three-dimensional (3D) motion capture system was utilized to capture the locomotion data. Furthermore, 63 spatiotemporal, kinematic, and nonlinear parameters were extracted, including lower limb joint angles in the sagittal, coronal, and transverse planes. Then, the Shapley Additive exPlanations (SHAP) value was utilized for feature selection and reduction of the dimensionality of features, and five traditional shallow classifiers, including support vector machine (SVM), logistic regression (LR), k-nearest neighbor (KNN), decision tree (DT), and random forest (RF), were used to classify gait patterns between CSM patients and HCs. On the basis of the 10-fold cross-validation method, the highest average accuracy was achieved by SVM (95.56%). Our results demonstrated that the proposed method could effectively detect CSM and thus serve as an automated auxiliary tool for the clinical diagnosis of CSM.

In accordance with the actual production circumstances of enterprises, a scheduling problem model is designed for open-shop environments, considering AGV transport time. A Q-learning-based method is proposed for the resolution of such problems. Based on the characteristics of the problem, a hybrid encoding approach combining process encoding and AGV encoding is applied. Three pairs of actions are constituted to form the action space. Decay factors and a greedy strategy are utilized to perturb the decision-making of the intelligent agent, preventing it from falling into local optima while simultaneously facilitating extensive exploration of the solution space. Finally, the proposed method proved to be effective in solving the open-shop scheduling problem considering AGV transport time through multiple comparative experiments.

Electrical Discharge Machining (EDM) is a machining method commonly used to produce complex shapes and deep holes by eroding hard metals with an electric arc. There is a growing demand for process simulation using finite element models in order to improve the quality and efficiency of EDM, to reduce costs, to improve resource efficiency, and to facilitate its application in critical areas such as aerospace and mechanical engineering. Finite element models have greatly improved the prediction accuracy of EDM processes, simulated complex hybrid machining processes, and provided important guidance for the optimization of EDM processes. This paper systematically reviews the research progress of finite element modeling for EDM. Finite element method modeling is evaluated mainly in terms of four indicators: material removal rate, surface roughness, tool wear ratio, and recast layer thickness. Firstly, the importance and application of EDM are described, and the EDM finite element method modeling and its advantages are summarized. Then, the single-spark simulation model and the multi-spark simulation model of EDM are compared and discussed. Among the mainstream finite element models, the prediction error of the material removal rate for single-spark simulation ranges from 8.2% to 14.75%, while the prediction error of the recast layer thickness for multi-spark simulation can be as low as 1.98%. Finally, the applications of finite element modeling in EDM hybrid machining processes’ performance prediction and new material machining are summarized, and future research directions and trends in EDM finite element modeling are predicted.

Reducing the energy consumption and exhaust emission, and improving the combustion efficiency of internal combustion engine are important for solving the problems of climate change and environmental pollution. The piston ring-liner system is one of the most serious friction pairs in internal combustion engine, accounting for 26% of the total friction loss. Depositing strengthened coatings on the surface of piston rings is an effective method to reduce the friction coefficient and wear rate. This paper reviews the research progress of several representative technologies for preparing coatings, such as electroplating, physical vapor deposition (PVD), thermal spraying and chemical vapor deposition (CVD), and so on. Various coatings, such as Cr-Al 2 O 3 coating prepared by representative electroplating process, CrN and DLC coatings prepared by physical vapor deposition, and Mo-based and C-based coatings prepared by thermal spraying process, are briefly discussed. Furthermore, the positive and negative aspects of commonly used piston ring coatings are compared, and their development trends are summarized.

Imbalanced data cause low recognition of wind turbine blade cracking. Existing data-level augmentation methods, including sampling and generative strategies, may yield lots of high-confidence but low-value samples, which fail to improve the detection of blade cracking. Therefore, this paper designs a novel RTAE (roundtrip auto-encoder) method. Based on the idea of the roundtrip approach, we design two generator networks and two discriminator networks to ensure the cycle mapping between cracking samples and latent variables. Further, by leveraging cycle consistency loss, generated samples fit the distribution of historical cracking samples well. Thus, these generated samples effectively realize data augmentation and improve recognition of blade cracking. Additionally, we apply an auto-encoder method to reduce the dimension of historical samples and thus the complexity of the generator network and discriminator network. Through the analysis of real wind turbine blade cracking data, the recognition of cracking samples is improved by 19.8%, 23.8% and 22.7% for precision, recall and F1-score.

In recent years, infrared thermographic (IRT) technology has experienced notable advancements and found widespread applications in various fields, such as renewable industry, electronic industry, construction, aviation, and healthcare. IRT technology is used for defect detection due to its non-contact, efficient, and high-resolution methods, which enhance product quality and reliability. This review offers an overview of active IRT principles. It comprehensively examines four categories based on the type of heat sources employed: pulsed thermography (PT), lock-in thermography (LT), ultrasonically stimulated vibration thermography (UVT), and eddy current thermography (ECT). Furthermore, the review explores the application of IRT imaging in the renewable energy sector, with a specific focus on the photovoltaic (PV) industry. The integration of IRT imaging and deep learning techniques presents an efficient and highly accurate solution for detecting defects in PV panels, playing a critical role in monitoring and maintaining PV energy systems. In addition, the application of infrared thermal imaging technology in electronic industry is reviewed. In the development and manufacturing of electronic products, IRT imaging is used to assess the performance and thermal characteristics of circuit boards. It aids in detecting potential material and manufacturing defects, ensuring product quality. Furthermore, the research discusses algorithmic detection for PV panels, the excitation sources used in electronic industry inspections, and infrared wavelengths. Finally, the review analyzes the advantages and challenges of IRT imaging concerning excitation sources, the PV industry, the electronics industry, and artificial intelligence (AI). It provides insights into critical issues requiring attention in future research endeavors.

In order to solve difficulties of going to bed and getting up for the elderly，a device is designed to assist them in going to bed. The track of the elderly's leg going to bed is analyzed. Based on mathematical modeling，the leg lift trajectory is simulated by intersection curves between spherical surface and conical surface，a spatial linkage is designed to help leg lift and its specific structure design and motion simulation are analyzed. The simulation results show that the device can realize leg lift trajectory and run smoothly，the theoretical feasibility is verified. The physical construction and practical test are carried out，it is proved that the device has clever mechanism and compact structure and can realize auxiliary leg lift，can be adapted to different bed types and has a broad application prospect.

This paper concentrates on the study of adaptive control for the synchronization of fractional-order neural networks. Instead of classical adaptive control updating method, an intermittent-active updating strategy is proposed to adaptively tune the control gain in a fractional-order fashion. Moreover, quantization is brought into the control design to take into account the restricted bandwidth in signal transmission. Note that the suggested controller is basic yet effective in terms of the fractional-order system. The main theorem is established with the method of reduction to absurdity as well as Lyapunov stability theorem. Finally, simulation calculation is conducted to validate the effectiveness of our proposed method.

This paper proposes a time-varying heterogeneous alternation controller for the synchronization of delayed neural networks (DNNs). Different from the mixture of traditional impulse and intermittent control, we consider a time-varying intermittent controller which is more representative than traditional periodic or aperiodic intermittent controllers. To make the system under study more applicable, we consider the impact of time-varying delay. After doing a theoretical analysis, the sufficient condition of the synchronization of DNNs is obtained. Finally, two simulations are offered to verify the validity of our results.

ObjectivesTo investigate whether combining radiomics extracted from ultrafast dynamic contrast-enhanced MRI (DCE-MRI) with an artificial neural network enables differentiation of MR BI-RADS 4 breast lesions and thereby avoids false-positive biopsies.MethodsThis retrospective study consecutively included patients with MR BI-RADS 4 lesions. The ultrafast imaging was performed using Differential sub-sampling with cartesian ordering (DISCO) technique and the tenth and fifteenth postcontrast DISCO images (DISCO-10 and DISCO-15) were selected for further analysis. An experienced radiologist used freely available software (FAE) to perform radiomics extraction. After principal component analysis (PCA), a multilayer perceptron artificial neural network (ANN) to distinguish between malignant and benign lesions was developed and tested using a random allocation approach. ROC analysis was performed to evaluate the diagnostic performance.Results173 patients (mean age 43.1 years, range 18–69 years) with 182 lesions (95 benign, 87 malignant) were included. Three types of independent principal components were obtained from the radiomics based on DISCO-10, DISCO-15, and their combination, respectively. In the testing dataset, ANN models showed excellent diagnostic performance with AUC values of 0.915-0.956. Applying the high-sensitivity cutoffs identified in the training dataset demonstrated the potential to reduce the number of unnecessary biopsies by 63.33%-83.33% at the price of one false-negative diagnosis within the testing dataset.ConclusionsThe ultrafast DCE-MRI radiomics-based machine learning model could classify MR BI-RADS category 4 lesions into benign or malignant, highlighting its potential for future application as a new tool for clinical diagnosis.

A cerebral contrast-enhanced electrical impedance tomography perfusion method is developed for acute ischemic stroke during intravenous thrombolytic therapy. Several clinical contrast agents with stable impedance characteristics and high-conductivity contrast were screened experimentally as electrical impedance contrast agent candidates. The electrical impedance tomography perfusion method was tested on rabbits with focal cerebral infarction, and its capability for early detection was verified based on perfusion images. The experimental results showed that ioversol 350 performed significantly better as an electrical impedance contrast agent than other contrast agents (p

BackgroundReal-time detection of cerebral blood perfusion can prevent adverse reactions, such as cerebral infarction and neuronal apoptosis. Our previous clinical trial have shown that the infusion of therapeutic fluid can significantly change the impedance distribution in the brain. However, whether this alteration implicates the cerebral blood perfusion remains unclear. To explore the feasibility of monitoring cerebral blood perfusion, the present pilot study established a novel cerebral contrast-enhanced electrical impedance tomography (C-EIT) technique.Materials and methodsRabbits were randomly divided into two groups: the internal carotid artery non-occlusion (ICAN) and internal carotid artery occlusion (ICAO) groups. Both of groups were injected with glucose, an electrical impedance-enhanced contrast agent, through the right internal carotid artery under EIT monitoring. The C-EIT reconstruction images of the rabbits brain were analyzed according to the collected raw data. The paired and independent t-tests were used to analyze the remodeled impedance values of the left and right cerebral hemispheres within and between studied groups, respectively. Moreover, pathological examinations of brain were performed immediately after C-EIT monitoring.ResultsAccording to the reconstructed images, the impedance value of the left cerebral hemisphere in the ICAN group did not change significantly, whereas the impedance value of the right cerebral hemisphere gradually increased, reaching a peak at approximately 10 s followed by gradually decreased. In the ICAO group, the impedance values of both cerebral hemispheres increased gradually and then began to decrease after reaching the peak value. According to the paired t-test, there was a significant difference (P < 0.001) in the remodeling impedance values between the left and right hemispheres in the ICAN group, and there was also a significant difference (P < 0.001) in the ICAO group. According to the independent t-test, there was a significant difference (P < 0.001) of the left hemispheres between the ICAN and ICAO groups.ConclusionThe cerebral C-EIT proposed in this pilot study can reflect cerebral blood perfusion. This method has potential in various applications in the brain in the future, including disease progression monitoring, collateral circulation judgment, tumor-specific detection, and brain function research.

Current therapy for ischemic stroke primarily relies on tissue plasminogen activator (tPA), but it is limited by narrow treatment time window, bleeding complications and neurotoxicity. The preliminary study of tPA plus Danhong injection (DHI) shows that it can significantly reduce the side effects of tPA and improve its thrombolytic effect, but the mechanism of this action has not been further studied. In this study, the rats were randomly divided into sham group, vehicle group, DHI group (4 mL/kg), tPA group (5 mg/kg) and DHI+tPA group (4 mL/kg+ 2.5 mg/kg), administered intravenously 4.5 h since focal embolic stroke modeling. After 3 days and 7 days of cerebral ischemia, the neurological function of each treatment group was significantly improved compared with the vehicle group. The combination of DHI and tPA significantly reduced Evans blue (EB) penetration as well as the expressions of the proteins MMP-9, PAI-1 and P-selectin, while upregulating the expressions of claudin-5, occludin, and ZO-1 mRNA. Furthermore, the effect of continuous 7-day treatment was more conspicuous than 3-day treatment. Then, it significantly reduced the expressions of the proteins DLL-4 and VEGFR-2, increased the expressions of Notch-1, HIF-1α and HES-1 mRNA, and promoted the expressions of VEGF/HIF-1α-positive cells at 14 days following stroke. Hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM) also showed that it improved pathological changes of ischemic brain tissue and the cerebral cortex micro-structure. These indicate that DHI combined with tPA may significantly ameliorate blood-brain barrier (BBB) disruption by activating Notch-VEGF signaling pathway to promote angiogenesis for long-term outcomes.

Low-molecular-weight glutenin subunits (LMW-GS) account for 40% of the total wheat grain gluten protein fraction, which plays a significant role in the formation of noodle processing quality. The goal of this study was to clarify the effects of the major LMW-GS encoded by Glu-A3 on gluten and Chinese fresh noodle (CFN) quality. Four near-isogenic lines (NILs) were used as materials in this study, respectively carrying alleles Glu-A3a, Glu-A3b, Glu-A3c, and Glu-A3e, against the background of wheat variety Xiaoyan 22. The grain protein and its component contents and the gluten content, gluten index, farinograph properties, cooking quality, and textural quality of CFN were investigated. The results show that the ratios of glutenin to gliadin (Glu/Gli) in the NILs ranked them as Glu-A3b > Glu-A3c/Glu-A3a > Glu-A3e, and the unextractable polymeric protein content (UPP%), gluten index (GI), and farinograph quality in the NILs ranked them as Glu-A3b > Glu-A3c > Glu-A3a/Glu-A3e. Compared to Glu-A3b and Glu-A3a, the NILs carrying alleles Glu-A3c and Glu-A3e had better cooking and texture properties in CFN. All these findings suggest that the introduction of alleles Glu-A3c or Glu-A3e is an efficient method for quality improvement in CFN, which provides an excellent subunit selection for improving CFN quality.

Integrated process planning and scheduling (IPPS) is important for modern manufacturing companies to achieve manufacturing efficiency and improve resource utilization. Meanwhile, multiple objectives need to be considered in the realistic decision-making process for manufacturing systems. Based on the above realistic manufacturing system requirements, it becomes increasingly important to develop effective methods to deal with multi-objective IPPS problems. Therefore, an improved NSGA-II (INSGA-II) algorithm is proposed in this research, which uses the fast non-dominated ranking method for multiple optimization objectives as an assignment scheme for fitness. A multi-layer integrated coding method is adopted to address the characteristics of the integrated optimization model, which involves many optimization parameters and interactions. Elite and mutation strategies are employed during the evolutionary process to enhance population diversity and the quality of solutions. An external archive is also used to store and update the Pareto solution. The experimental results on the Kim test set demonstrate the effectiveness of the proposed INSGA-II algorithm.

Abstract Background Pears and apples are both perennial deciduous trees of the Rosaceae family, and both are important economic fruit trees worldwide. The emergence of many varieties in the market has been mostly domesticated from wild to cultivated and regulated by the differential expression of genes. However, the molecular process and pathways underlying this phenomenon remain unclear. Four typical wild and cultivar pear and apple trees at three developmental stages were used in our study to investigate the molecular process at the transcriptome level. Result Physiological observations indicated the obvious differences of size, weight, sugar acid content and peel color in wild and cultivar fruit among each developmental stage. Using next-generation sequencing based RNA-seq expression profiling technology, we produced a transcriptome in procession of a large fraction of annotated pear and apple genes, and provided a molecular basis underlying the phenomenon of wild and cultivar fruit tree differences. 5921 and 5744 differential expression genes were identified in pear and apple at three developmental stages respectively. We performed temporal and spatial differential gene expression profiling in developing fruits. Several key pathways such as signal transduction, photosynthesis, translation and many metabolisms were identified as involved in the differentiation of wild and cultivar fruits. Conclusion In this study, we reported on the next-generation sequencing study of the temporal and spatial mRNA expression profiling of pear and apple fruit trees. Also, we demonstrated that the integrated analysis of pear and apple transcriptome, which strongly revealed the consistent process of domestication in Rosaceae fruit trees. The results will be great influence to the improvement of cultivar species and the utilization of wild resources.

Overnutrition-related obesity has become a worldwide epidemic, and its prevalence is expected to steadily rise in the future. It is widely recognized that obesity exerts negative impacts on metabolic disorders such as type 2 diabetes mellitus (T2DM) and cardiovascular diseases. However, relatively fewer reports exist on the impairment of brain structure and function, in the form of memory and executive dysfunction, as well as neurogenerative diseases. Emerging evidence indicates that besides obesity, overnutrition diets independently induce cognitive impairments via multiple mechanisms. In this study, we reviewed the clinical and preclinical literature about the detrimental effects of obesity or high-nutrition diets on cognitive performance and cerebral structure. We mainly focused on the role of brain insulin resistance (IR), microbiota-gut-brain axis, and neuroinflammation. We concluded that before the onset of obesity, short-term exposure to high-nutrition diets already blunted central responses to insulin, altered gut microbiome composition, and activated inflammatory mediators. Overnutrition is linked with the changes in protein expression in brain insulin signaling, leading to pathological features in the brain. Microbiome alteration, bacterial endotoxin release, and gut barrier hyperpermeability also occur to trigger mental and neuronal diseases. In addition, obesity or high-nutrition diets cause chronic and low-grade systematic inflammation, which eventually spreads from the peripheral tissue to the central nervous system (CNS). Altogether, a large number of unknown but potential routes interact and contribute to obesity or diet-induced cognitive impairment. The challenge for future research is to identify effective interventions involving dietary shifts and personalized therapy targeting the underlying mechanisms to prevent and improve cognition deficits.

Halomonas bluephagenesis TD01 is one of the ideal chassis for low-cost industrial production based on “Next Generation Industrial Biotechnology,” yet the limited genetically regulatory parts such as transcriptional terminators, which are crucial for tuned regulations on gene expression, have hampered the engineering and applications of the strain. In this study, a series of intrinsic Rho-independent terminators were developed by either genome mining or rational design, and seven of them proved to exhibit higher efficiencies than the canonical strong T7 terminator, among which three terminators displayed high efficiencies over 90%. A preliminary modeling on the sequence-efficiency relationship of the terminators suggested that the poly U sequence regularity, the length and GC content of the stem, and the number and the size of hairpin loops remarkably affected the termination efficiency (TE). The rational and de novo designs of novel synthetic terminators based on the sequence-efficiency relationship and the “main contributor” engineering strategy proved to be effective, and fine-tuned polyhydroxylkanoates production was also achieved by the regulation of these native or synthetic terminators with different efficiencies. Furthermore, a perfectly positive correlation between the promoter activity and the TE was revealed in our study. The study enriches our knowledge of transcriptional termination via its sequence–strength relationship and enables the precise regulation of gene expression and PHA synthesis by intrinsic terminators, contributing to the extensive applications of H. bluephagenesis TD01 in the low-cost production of various chemicals.

In this research, a model is proposed using piecewise fractal theory that considers abrasive and adhesive wear. The model demonstrated improved wear computation accuracy of a contact mechanical seal end face. The validity of the model was established by comparing the simulation results with experimental data and the conventional MB and Archard models. The loading effect and surface morphology parameters involved in wear were also investigated. Results show that severe wear occurs with increasing load ratio, large fractal dimensions, and a higher scale coefficient of the surface morphology. The findings offer a novel method for precisely calculating and projecting the amount of wear of a contact mechanical seal and predicting its wear behavior.

Abstract Background Muscle stem cells (MuSCs) are absolutely required for the formation, repair, and regeneration of skeletal muscle tissue. Increasing evidence demonstrated that tissue stem cells, especially mesenchymal stem cells (MSCs), can exert therapeutic effects on various degenerative and inflammatory disorders based on their immunoregulatory properties. Human mesenchymal stem cells (hMSCs) treated with interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were reported to possess anti-inflammatory functions by producing TNF-stimulated gene 6 (TSG-6). However, whether human muscle stem cells (hMuSCs) also possess TSG-6 mediated anti-inflammatory functions has not been explored. Methods The ulcerative colitis mouse model was established by subjecting mice to dextran sulfate sodium (DSS) in drinking water for 7 days. hMuSCs were pretreated with IFN-γ and TNF-α for 48 h and were then transplanted intravenously at day 2 of DSS administration. Body weights were monitored daily. Indoleamine 2,3-dioxygenase (IDO) and TSG-6 in hMuSCs were knocked down with short hairpin RNA (shRNA) and small interfering RNA (siRNA), respectively. Colon tissues were collected for length measurement and histopathological examination. The serum level of IL-6 in mice was measured by enzyme-linked immunosorbent assay (ELISA). Real-time PCR and Western blot analysis were performed to evaluate gene expression. Results hMuSCs treated with inflammatory factors significantly ameliorated inflammatory bowel disease (IBD) symptoms. IDO and TSG-6 were greatly upregulated and required for the beneficial effects of hMuSCs on IBD. Mechanistically, the tryptophan metabolites, kynurenine (KYN) or kynurenic acid (KYNA) produced by IDO, augmented the expression of TSG-6 through activating their common receptor aryl hydrocarbon receptor (AHR). Conclusion Inflammatory cytokines-treated hMuSCs can alleviate DSS-induced colitis through IDO-mediated TSG-6 production.

Abstract Triboelectric nanogenerator (TENG) is a micro/nano electromechanical power system that converts mechanical energy into electricity based on contact electrification and electrostatic induction. At present, research on improving TENG performance mainly focus on material optimization and texture fabrication. This paper proposes a simple material optimization method based on regulating the ratio of elastomer base to curing agent (base/agent ratio) of Polydimethylsiloxane (PDMS) to improve the performance of TENG with rectangular groove textures, and the influence of texture sizes on TENG output is explored. By analyzing the contact behavior, dielectric, and mechanical property, the influence mechanism of PDMS base/agent ratios and texture sizes on TENG performance is revealed. Results show that PDMS base/agent ratios affect TENG output mainly through material dielectric properties, while texture sizes mainly by contact behaviors. As the base/agent ratio decreases, although the real contact area and displacement of PDMS exhibit slight reductions, the relative permittivity of PDMS increases, and thus the surface charge density and performance of TENG increases. As the boss width increases or the groove width decreases, the displacement of PDMS declines, which would lead to the slight drop of the surface charge density, but the real contact area increases, which still results in improved TENG output.

Ochratoxin A (OTA) is a harmful mycotoxin, which is mainly secreted by Penicillium and Aspergillus species. In this work, an electrochemical aptasensor is presented for OTA detection based on Au nanoparticles (AuNPs) modified zeolite imidazolate frameworks (ZIFs) ZIF-8 platform and duplex-specific nuclease (DSN) triggered hybridization chain reaction (HCR) signal amplification. G-quadruplex-hemin assembled HCR nanowire acted as a nicotinamide adenine dinucleotide (NADH) oxidase and an HRP-mimicking DNAzyme. Besides, thionine (Thi) was enriched as a redox probe for signal amplification in this pseudobienzyme electrocatalytic system. Under the optimal conditions, the analytical response ranged from 1 to 107 fg ml−1 with a detection limit of 0.247 fg ml−1. Furthermore, the aptasensor was proven to be applied in real wheat samples with a recovery between 96.8 and 104.2%, illustrating the potential prospects in practical detection.

Abstract Cytokines produced by immune cells have been demonstrated to act on muscle stem cells (MuSCs) and direct their fate and behavior during muscle repair and regeneration. Nevertheless, it is unclear whether and how MuSCs can also in turn modulate the properties of immune cells. Here, we showed that in vitro expanded MuSCs exhibited a potent anti‐inflammatory effect when infused into mice suffering from inflammatory bowel disease (IBD). Supernatant conditioned by MuSCs similarly ameliorated IBD. This beneficial effect of MuSCs was not observed when macrophages were depleted. The MuSC supernatant was found to greatly attenuate the expression of inflammatory cytokines but increase the expression of programmed death‐ligand 1 in macrophages treated with lipopolysaccharide and interferon gamma. Further analysis revealed that MuSCs produce a large amount of insulin‐like growth factor‐2 (IGF‐2) that instructs maturing macrophages to undergo oxidative phosphorylation and thus acquire anti‐inflammatory properties. Interestingly, the IGF‐2 production by MuSCs is much higher than by mesenchymal stem cells. Knockdown or neutralization of IGF‐2 abrogated the anti‐inflammatory effects of MuSCs and their therapeutic efficacy on IBD. Our study demonstrated that MuSCs possess a strong anti‐inflammatory property and the bidirectional interactions between immune cells and MuSCs have important implications in muscle‐related physiological and pathological conditions.

PurposeThe clinical significance of endovascular therapy in young patients with symptomatic intracranial atherosclerotic stenosis is not clear. We aimed to report our preliminary findings on the safety and effectiveness of a new endovascular treatment strategy, drug-coated balloon (DCB)-oriented angioplasty for young adults with severe symptomatic atherosclerotic middle cerebral artery (MCA) stenosis.MethodsWe retrospectively retrieved the data of seven young patients aged 21–32 years old with severe symptomatic atherosclerotic MCA stenosis treated with DCB-oriented angioplasty from January 2018 to October 2020. We collected clinical presentations, perioperative complications, and clinical and radiological outcomes.ResultsThe DCB was successfully dilated at the lesions in all seven patients and good antegrade perfusion was achieved in five. The other two patients underwent remedial stent implantation due to residual stenosis >50% and unstable antegrade perfusion after DCB dilatation. However, none of the patients had perioperative complications. There were no recurrent ischemic symptoms after a mean clinical follow-up period of 15.4 ± 6.9 months. Repeat vascular images of the patients showed no restenosis at 3- or 6-month imaging follow-up periods. High-resolution MRI (HRMRI) was completed in all the patients before the angioplasty procedure and at follow-up. Focal eccentric wall thickening was present at the site of stenosis preoperatively; however, the plaques had disappeared by the time of follow-up for all patients.ConclusionDCB-oriented angioplasty may be safe and effective for young patients with severe symptomatic atherosclerotic MCA stenosis.

Background: Long non-coding RNAs (lncRNAs) are key regulators of pancreatic cancer development and are involved in ferroptosis regulation. LncRNA transcript levels serve as a prognostic factor for pancreatic cancer. Therefore, identifying ferroptosis-related lncRNAs (FRLs) with prognostic value in pancreatic cancer is critical.Methods: In this study, FRLs were identified by combining The Cancer Genome Atlas (TCGA) and FerrDb databases. For training cohort, univariate Cox, Lasso, and multivariate Cox regression analyses were applied to identify prognosis FRLs and then construct a prognostic FRLs signature. Testing cohort and entire cohort were applied to validate the prognostic signature. Moreover, the nomogram was performed to predict prognosis at different clinicopathological stages and risk scores. A co-expression network with 76 lncRNA-mRNA targets was constructed.Results: Univariate Cox analysis was performed to analyze the prognostic value of 193 lncRNAs. Furthermore, the least absolute shrinkage and selection operator and the multivariate Cox analysis were used to assess the prognostic value of these ferroptosis-related lncRNAs. A prognostic risk model, of six lncRNAs, including LINC01705, AC068620.2, TRAF3IP2-AS1, AC092171.2, AC099850.3, and MIR193BHG was constructed. The Kaplan Meier (KM) and time-related receiver operating characteristic (ROC) curve analysis were performed to calculate overall survival and compare high- and low-risk groups. There was also a significant difference in survival time between the high-risk and low-risk groups for the testing cohort and the entire cohort, with AUCs of .723, .753, respectively. Combined with clinicopathological characteristics, the risk model was validated as a new independent prognostic factor for pancreatic adenocarcinoma through univariate and multivariate Cox regression. Moreover, a nomogram showed good prediction.Conclusion: The signature of six FRLs had significant prognostic value for pancreatic adenocarcinoma. They may be a promising therapeutic target in clinical practice.

Background. Vaspin is an important adipokine that is involved in cardiovascular diseases. This study is aimed at investigating whether vaspin participates in sepsis-induced cardiac injury and explored the possible mechanism. Methods. First, cecal ligation and puncture (CLP) and lipopolysaccharide (LPS) were used to establish a mouse model of sepsis, and cardiac vaspin expression was examined. In addition, after pretreatment with vaspin or phosphate-buffered saline (PBS), wild-type (WT) mice underwent CLP to establish a septic model and received sham as a control. Finally, WT mice and kallikrein 7 (KLK7-/-) mice were underwent CLP with or without vaspin pretreatment. Results. Mice that underwent CLP and were administered LPS exhibited increased vaspin expression in both the heart and serum compared with sham- or saline-treated mice. In CLP mice, pretreatment with vaspin reduced mortality and alleviated the expression of cardiac injury markers and cardiac dysfunction. In addition, vaspin reduced the cardiac levels of CD45+ cells and CD68+ cells, alleviated the cardiac inflammatory response, and reduced cardiomyocyte apoptosis. The protective effects of vaspin on CLP mice were masked by the deletion of KLK7, which was demonstrated to be a downstream signal of vaspin. Conclusions. Vaspin alleviates cardiac inflammation and plays a protective role in sepsis-induced cardiac injury by reducing KLK7 expression.

Coptis chinensis Franch (CCF) is extensively used in the treatment of inflammatory-related diseases. Accumulating studies have previously demonstrated the anti-inflammatory properties of CCF, yet data on its exact targets against urinary tract infections (UTIs) remain largely unknown. Therefore, the present study decodes the potential targets of action of CCF against UTIs by network pharmacology combined with experiment evaluations. Based on the pharmacology network analysis, the current study yielded six core ingredients: quercetin, palmatine (R)-canadine, berlambine, berberine, and berberrubine. The protein–protein interaction network (PPI) was generated by the string database, and then, four targets (IL6, FOS, MYC, and EGFR) were perceived as the major CCF targets using the CytoNCA plug-in. The results of molecular docking showed that the six core constituents of CCF had strong binding affinities toward the four key targets of UTIs after docking into the crystal structure. The enrichment analysis indicated that the possible regulatory mechanisms of CCF against UTIs were based on the modules of inflammation, immune responses, and apoptosis among others. Experimentally, the Escherichia coli (E. coli) strain CFT073 was applied to establish in vivo and in vitro models. In vivo results revealed that the key targets, IL6 and FOS, are significantly upregulated in rat bladder tissues of UTIs, whereas the expression of MYC and EGFR remained steady. Last, in vitro results further confirmed the therapeutic potential of CCF by reducing the expression of IL6 and FOS. In conclusion, IL6 and FOS were generally upregulated in the progression of E. coli–induced UTIs, whereas the CCF intervention exerted a preventive role in host cells stimulated by E. coli, partially due to inhibiting the expression of IL6 and FOS.