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Preventive health workers rather than general practitioners (GPs) are the principal providers of vaccines in China, which may be a determinant of the unmet demand for vaccination, especially for adults, in recent years. GPs’ preferences had a significant influence on alternative approaches to adult vaccination delivery. To better understand GP’s preferences for adult vaccination services, we employed a discrete choice experiment with seven attributes: income, setting, information system, workshop, workload, performance measurement, and managerial support. Mixed logit models and latent class models were used for statistical analyses. In general, support from primary healthcare managers was the strongest driver of choice, followed by a 10% increase in workload, separate adult vaccination clinic, 5% increase in workload, and independent information system. Monthly income was significantly associated with provision of adult vaccination services. Based on the influence of latent factors, GPs fell into three classes that were correlated with GPs’ years of practice, workload, income satisfaction, and knowledge-attitude-practicescore. Classes 1 and 2 valued the service setting and performance measurement differently, while Class 3 valued the service setting only (preferred separate adult vaccination clinics to provide service). This study generated actionable information to guide innovation in the adult vaccination delivery system in China.

As an integration of artificial intelligence and advanced manufacturing technology, intelligent manufacturing has realized the innovation of manufacturing mode and created conditions for the green development of industry. After constructing a theoretical framework between intelligent manufacturing and industrial green total factor productivity, this paper uses panel data of 30 provinces in China from 2006 to 2020, and expresses the level of intelligent manufacturing with industrial robot density, to discuss the economic effects and mechanisms of intelligent manufacturing. The results show that intelligent manufacturing has a positive effect on industrial green total factor productivity, and the panel quantile regression model indicates that there is an increasing marginal effect. With the quantile points going from low to high, the coefficient and statistical significance become larger. Human capital is the mechanism for intelligent manufacturing to improve industrial green total factor productivity. Green technology innovation and producer service industry agglomeration have strengthened the positive effect. There is also heterogeneity in the effect, and the stronger the effect in regions launched local pilot schemes for carbon emissions trading and industrial green transformation development policy. In order to give full play to the technological dividend and empower sustainable industrial development, the paper argues that we need to accelerate the integration of artificial intelligence and manufacturing technology, thus improving the level of industrial intelligence and empowering green development.

Although fine particulate matter (PM2.5) is a neurotoxicant, little is known about whether early-life PM2.5 exposure is associated with an increased risk of developmental coordination disorder (DCD). We conducted a cohort study of 109 731 children aged 3–5 years from 551 county-level cities in China between April 2018 and December 2019. Residential PM2.5 exposure was estimated using a hybrid satellite-based exposure model. Children’s motor performance was assessed using the Little DCD Questionnaire (LDCDQ). Linear mixed-effect models and generalized linear mixed models with a binomial distribution were used to examine the associations of PM2.5 exposure with LDCDQ scores and risk of DCD, respectively. Both prenatal and postnatal exposure to a higher level of PM2.5 was significantly associated with reduced total LDCDQ score, and the impacts were evident on subscales of control during movement and general coordination function but not fine motor function. For example, an interquartile range increase in PM2.5 exposure in ages 0–3 was associated with a 0.19 (95% confidence interval [CI]: 0.05, 0.33) decrement in the total score. Additionally, higher PM2.5 exposure was associated with increased risk of DCD, and the adjusted odds ratios were 1.06 (95% CI: 1.01, 1.10) and 1.06 (95% CI: 1.01, 1.13) for each interquartile range increase in PM2.5 exposure during the first trimester and the first 3 years, respectively. Children who were from rural areas, had neonatal intensive care unit admission, or were exclusively breastfed for less than 6 months appeared to be more susceptible to PM2.5 exposure than their counterparts. Our findings provide robust evidence that early-life PM2.5 exposure contributes to an elevated risk of DCD.

Abstract Hypertension is the most common comorbidity in patients with coronavirus disease 2019 (COVID‐19) and increases in‐hospital mortality. Day‐by‐day blood pressure (BP) variability (BPV) is associated with clinical outcomes in hypertensive patients. However, little information is available on the association of BPV with the outcomes of COVID‐19 patients with hypertension. This study aimed to demonstrate whether day‐by‐day in‐hospital BPV had prognostic significance in these patients. The authors included 702 COVID‐19 patients with hypertension from Huoshenshan Hospital (Wuhan, China), who underwent valid in‐hospital BP measurements on at least seven consecutive days. Day‐by‐day BPV was assessed by standard deviation (SD), coefficient of variation (CV), and variation independent of mean (VIM). Overall, patients with severe COVID‐19 and non‐survivors had higher BPV than moderate cases and survivors, respectively. Additionally, higher BPV was correlated with greater age and higher levels of C‐reactive protein, procalcitonin, high‐sensitive cardiac troponin I, and B‐type natriuretic peptide. In multivariable Cox regression, SD of systolic BP (SBP) was predictive of mortality [hazard ratio (HR) 1.17, 95% confidence interval (CI) 1.05–1.30] as well as acute respiratory distress syndrome (ARDS) (HR 1.09, 95% CI 1.01–1.16). Similar trends were observed for CV and VIM of SBP, but not indices of diastolic BP variability. The authors demonstrated that day‐by‐day in‐hospital SBP variability can independently predict mortality and ARDS in COVID‐19 patients with hypertension. And high BPV might be correlated with severe inflammation and myocardial injury. Further studies are needed to clarify whether early reduction of BPV will improve the prognosis of these patients.

Abstract Glioblastoma multiforme (GBM) is the most aggressive malignant primary brain tumor of the central nervous system. Despite continuous progression in treatment options for GBM like surgery, radiotherapy, and chemotherapy, this disease still has a high rate of recurrence. The endoplasmic reticulum (ER) stress pathway is associated with chemotherapeutic drug resistance. The UBA1 inhibitor TAK-243 can induce strong ER stress. However, the sensitivity of TAK-243 varies greatly in different tumor cells. This study evaluated the antitumor effects of the GRP78 inhibitor, HA15, combined with TAK-243 on GBM in the preclinical models. HA15 synergistically enhanced the sensitivity of GBM cells to TAK-243. When compared with TAK-243 monotherapy, HA15 combined with TAK-243 significantly inhibited GBM cell proliferation. It also induced G2/M-phase arrest in the cell cycle. In vivo studies showed that HA15 combined with TAK-243 significantly inhibited the growth of intracranial GBM and prolonged survival of the tumor-bearing mice. Mechanistically, HA15 and TAK-243 synergistically activated the PERK/ATF4 and IRE1α/XBP1 signaling axes, thereby eventually activating PARP and the Caspase families, which induced cell apoptosis. Our data provided a new strategy for improving the sensitivity of GBM to TAK-243 treatment and experimental basis for further clinical trials to evaluate this combination therapy.

Peptide heterodimers are prevalent in nature, which are not only functional macromolecules but molecular tools for chemical and synthetic biology. Here the authors report de novo design and directed folding of peptide heterodimers crosslinked through multiple disulfide bonds, which can be explored as chemical tools for orthogonal labeling of proteins and preparing protein hybrids.

Abstract Background Emerging findings highlighted the associations of mental illness to nutrition and dysbiosis in the intestinal microbiota, but the underlying mechanisms, especially in schizophrenia (SZ), remain unclarified. Methods We conducted a case-control study of SZ patients (case to control=100:52) by performing sequencing of the gut metagenome; measurement of fecal and plasma non-targeted metabolome; including short-, medium-, and long-chain fatty acids; and targeted metabolites, along with recorded details of daily intakes of food. Results The metagenome analysis uncovered enrichment of asaccharolytic species and reduced abundance of carbohydrate catabolism pathways and enzymes in the gut of SZ patients, but increased abundance of peptidases in contrast to their significantly reduced protein intake. Fecal metabolome analysis identified increased concentrations of many protein catabolism products, including amino acids (AAs), urea, branched short-chain fatty acids, and various nitrogenous derivates of aromatic AAs in SZ patients. Protein synthesis, represented by the abundance of AA-biosynthesis pathways and aminoacyl-tRNA transferases in metagenome, was significantly decreased. The AUCs (area under the curve) of the diagnostic random forest models based on their abundance achieved 85% and 91%, respectively. The fecal levels of AA-fermentative enzymes and products uniformly showed positive correlations with the severity of psychiatric symptoms. Conclusions Our findings revealed apparent dysbiosis in the intestinal microbiome of SZ patients, where microbial metabolism is dominated by protein fermentation and shift from carbohydrate fermentation and protein synthesis in healthy conditions. The aberrant macronutrient metabolism by gut microbes highlights the importance of nutrition care and the potential for developing microbiota-targeted therapeutics in SZ.

Abstract Background Virtual reality (VR) surgery training has become a trend in clinical education. Many research papers validate the effectiveness of VR-based surgical simulators in training medical students. However, most existing articles employ subjective methods to study the residents’ surgical skills improvement. Few of them investigate how to improve the surgery skills on specific dimensions substantially. Methods Our paper resorts to physiological approaches to objectively study the quantitative influence and performance analysis of VR laparoscopic surgical training system for medical students. Fifty-one participants were recruited from a pool of medical students. They conducted four pre and post experiments in the training box. They were trained on VR-based laparoscopic surgery simulators (VRLS) in the middle of pre and post experiments. Their operation and physiological data (heart rate and electroencephalogram) are recorded during the pre and post experiments. The physiological data is used to compute cognitive load and flow experience quantitatively. Senior surgeons graded their performance using newly designed hybrid standards for fundamental tasks and Global operative assessment of laparoscopic skills (GOALS) standards for colon resection tasks. Finally, the participants were required to fill the questionnaires about their cognitive load and flow experience. Results After training on VRLS, the time of the experimental group to complete the same task could drop sharply (p < 0.01). The performance scores are enhanced significantly (p < 0.01). The performance and cognitive load computed from EEG are negatively correlated (p < 0.05). Conclusion The results show that the VRLS could highly improve medical students' performance and enable the participants to obtain flow experience with a lower cognitive load. Participants' performance is negatively correlated with cognitive load through quantitative physiological analysis. This might provide a new way of assessing skill acquirement.

Single qubit in solid-state materials recently emerges as a versatile platform for quantum information. Among them, the nitrogen vacancy (NV) centre in diamond has become a powerful tool in quantum sensing for detecting various physics parameters, including electric and magnetic fields, temperature, force, strain, with ultimate precision and resolutions. It has been widely used in different conditions, from samples in ambient to samples in ultra-high pressure and low temperature. It can detect quantum phase transitions as well as neuron activities. Here we give a general review on both the physics of the sensing mechanism and protocols and applications.

Abstract Background This study aimed to evaluate the clinical outcomes and assess preoperative characteristics that may predict outcomes in keratoconus 1 year after accelerated transepithelial corneal cross-linking (ATE-CXL). Methods This prospective study included 93 eyes of 84 consecutive keratoconus patients with 1-year follow-up after ATE-CXL. Preoperative characteristics included corneal astigmatism, anterior chamber depth, anterior chamber volume, radius of curvature, posterior elevation, central corneal thickness (CCT), thinnest corneal thickness, steepest meridian keratometry, flattest meridian keratometry, and the maximum keratometry (Kmax). Data were obtained preoperatively and at 1, 3, 6, and 12 months postoperatively. The patient eyes were grouped into 3 subgroups according to CCT and Kmax values to observe the changes of keratoconus progression. Results All patients were successfully operated without complications at any follow-up time point. Mean changes of Kmax from baseline at 6 and 12 months were − 0.60 ± 2.21 D (P = 0.011) and − 0.36 ± 1.58 D (P = 0.030), respectively. Eyes with a thinner CCT and higher Kmax values exhibited a tendency for topographic flattening of ≥1.0 D (P = 0.003; P = 0.003). In the subgroup comparison, the Kmax values decreased significantly at 6 and 12 months after ATE-CXL in the group with CCT ≤ 450 μm (P = 0.018 and P = 0.045); the Kmax values of the group with Kmax > 65.0 D decreased significantly at 6 months postoperatively (P = 0.025). Conclusion ATE-CXL is a safe and effective treatment for keratoconus patients. Patients with thinner CCT and higher Kmax values are more likely to benefit from ATE-CXL.

Abstract Systems neuroscience is focused on how ensemble properties in the brain, such as the activity of neuronal circuits, gives rise to internal brain states and behavior. Many of the studies in this field have traditionally involved electrophysiological recordings and computational approaches that attempt to decode how the brain transforms inputs into functional outputs. More recently, systems neuroscience has received an infusion of approaches and techniques that allow the manipulation (e.g., optogenetics, chemogenetics) and imaging (e.g., two-photon imaging, head mounted fluorescent microscopes) of neurons, neurocircuits, their inputs and outputs. Here, we will review novel approaches that allow the manipulation and imaging of specific molecular mechanisms in specific cells (not just neurons), cell ensembles and brain regions. These molecular approaches, with the specificity and temporal resolution appropriate for systems studies, promise to infuse the field with novel ideas, emphases and directions, and are motivating the emergence of a molecularly oriented systems neuroscience, a new discipline that studies how the spatial and temporal patterns of molecular systems modulate circuits and brain networks, and consequently shape the properties of brain states and behavior.

Abstract Background Ferroptosis and iron-metabolism are regulated by Long non-coding RNAs (lncRNAs) in ovarian cancer (OC). Therefore, a comprehensive analysis of ferroptosis and iron-metabolism related lncRNAs (FIRLs) in OC is crucial for proposing therapeutic strategies and survival prediction. Methods In multi-omics data from OC patients, FIRLs were identified by calculating Pearson correlation coefficients with ferroptosis and iron-metabolism related genes (FIRGs). Cox-Lasso regression analysis was performed on the FIRLs to screen further the lncRNAs participating in FIRLs signature. In addition, all patients were divided into two robust risk subtypes using the FIRLs signature. Receiver operator characteristic (ROC) curve, Kaplan–Meier analysis, decision curve analysis (DCA), Cox regression analysis and calibration curve were used to confirm the clinical benefits of FIRLs signature. Meanwhile, two nomograms were constructed to facilitate clinical application. Moreover, the potential biological functions of the signature were investigated by genes function annotation. Finally, immune microenvironment, chemotherapeutic sensitivity, and the response of PARP inhibitors were compared in different risk groups using diversiform bioinformatics algorithms. Results The raw data were randomized into a training set (n = 264) and a testing set (n = 110). According to Pearson coefficients between FIRGs and lncRNAs, 1075 FIRLs were screened for univariate Cox regression analysis, and then LASSO regression analysis was used to construct 8-FIRLs signature. It is worth mentioning that a variety of analytical methods indicated excellent predictive performance for overall survival (OS) of FIRLs signature (p

El-Shennawy et al. report that ACE2+ circulating extracellular vesicles (evACE2) are associated with COVID-19 severity and that evACE2 inhibits the infection of SARS-CoV-2 variants of concern at a higher efficacy than soluble ACE2.

Fish body length is an essential monitoring parameter in aquaculture engineering. However, traditional manual measurement methods have been found to be inefficient and harmful to fish. To overcome these shortcomings, this paper proposes a non-contact measurement method that utilizes binocular stereo vision to accurately measure the body length of fish underwater. Binocular cameras capture RGB and depth images to acquire the RGB-D data of the fish, and then the RGB images are selectively segmented using the contrast-adaptive Grab Cut algorithm. To determine the state of the fish, a skeleton extraction algorithm is employed to handle fish with curved bodies. The errors caused by the refraction of water are then analyzed and corrected. Finally, the best measurement points from the RGB image are extracted and converted into 3D spatial coordinates to calculate the length of the fish, for which measurement software was developed. The experimental results indicate that the mean relative percentage error for fish-length measurement is 0.9%. This paper presents a method that meets the accuracy requirements for measurement in aquaculture while also being convenient for implementation and application.

Abstract Background Hip fracture is common in older adults, and can cause severe post-fracture pain. Fascia iliaca nerve block has consequently been used for preoperative analgesia. Methods We performed a randomized, controlled, double-blind clinical trial and recruited older patients with hip fractures. These patients were randomized into two groups and received ultrasound-guided fascia iliaca compartment block using either the supra-inguinal approach (group F) or the classical approach (group C). Heart rate, blood pressure, and resting and exercising visual analog scales were recorded before the procedure and at 30 min, and 6, 12, and 24 h after completion of the procedure. We recorded the duration of the procedure—as well as complications such as bleeding, hypotension, and intractable vomiting; the sleep duration in a 24 h period was also documented. Results A total of 38 patients completed the trial, and we observed no differences in the baseline characteristics or pre-procedural measurements between the two groups. Compared with the patients in group C, patients in group F exhibited significantly lower exercising VAS scores at 6 and 12 h after the procedure, faster heart rates at 6 and 24 h after the procedure, a longer procedural duration, and a longer sleep duration. There were no differences in the frequencies of complications between the two groups. The percentages of patients who took oral analgesics and the numbers of medications consumed were also not different between the two groups. Conclusions The supra-inguinal FICB provided effective analgesia and improved exercise tolerance compared with the classical approach. Trial registration The trial was registered at the Chinese Clinical Trial Registry (registration number: ChiCTR2100045644, registration date: 2021 April 20).

The spatial organization of cell surface receptors is critical for cell signaling and drug action. Here, the authors develop an optoproteomic method for mapping surface protein interactions, revealing cellular responses to antibodies, drugs and viral particles as well as immunosynapse signaling events.

Abstract Purpose Ovarian cancer (OC) is the most common malignancy in women with high mortality. Increasing studies have revealed that long non-coding RNA (lncRNA) MNX1-AS1 has a promoting effect on various cancers. However, the mechanisms of MNX1-AS1 in OC are still unclear. Therefore, this study focused on exploring the mechanisms of MNX1-AS1 in OC. Materials and methods The expression of SOX12 at the protein level was detected by western blot. Cell proliferation was detected by CCK8 assay and colony formation assay. Cell cycle and cell apoptosis were detected by flow cytometry. Wound-healing assay, transwell assay and western blot were used to detect the ability of cell migration and invasion. The target binding was confirmed through the luciferase reporter assay. Results The expression of MNX1-AS1 was increased in OC tumor tissues and cells. Elevated MNX1-AS1 expression is associated with advanced stage and lower overall survival rate. Knockdown of MNX1-AS1 inhibited cell proliferation, migration and invasion, blocked cell cycle, and promoted cell apoptosis in SKOV-3 and OVCAR-3 cells. MNX1-AS1 was competitively binding with miR-744-5p, and its downstream target gene was SOX12. miR-544-5p expression was decreased, while SOX12 expression was increased in OC tumor tissues and cells. Overexpression of miR-744-5p inhibited cell proliferation, migration, invasion and promoted cell apoptosis in SKOV-3 and OVCAR-3 cells. Conclusion MNX1-AS1 promoted the development of OC through miR-744-5p/SOX12 axis. This study revealed a novel mechanism of MNX1-AS1 in OC, which may provide a new treatment or scanning target for OC.

Epithelial–mesenchymal transition (EMT) mediated by fluid shear stress (FSS) in the tumor microenvironment plays an important role in driving metastasis of the malignant tumor. As a mechanotransducer, Yes‐associated protein (YAP) is known to translocate into the nucleus to initiate transcription of genes involved in cell proliferation upon extracellular biophysical stimuli. Here, we showed that FSS facilitated cytoskeleton rearrangement in hepatocellular carcinoma cells, which led to the release of YAP from its binding partner, integrin β subunit, in the cytomembrane. Moreover, we found that upregulation of guanine nucleotide exchange factor (GEF)‐H1, a microtubule‐associated Rho GEF, is a critical step in the FSS‐induced translocation of YAP. Nuclear YAP activated the expression of the EMT‐regulating transcription factor SNAI1, but suppressed the expression of N6‐methyladenosine (m6A) modulators; together, this promoted the expression of EMT‐related genes. We also observed that FSS‐treated HepG2 cells showed markedly increased tumorigenesis and metastasis in vivo. Collectively, our findings unravel the underlying molecular processes by which FSS induces translocation of YAP from the cytomembrane to the nucleus, contributes to EMT and enhances metastasis in hepatocellular carcinoma.

Hot spot gene mutations in splicing factor 3b subunit 1 (SF3B1) are observed in many types of cancer and create abundant aberrant mRNA splicing, which is profoundly implicated in tumorigenesis. Here, we identified that the SF3B1 K700E (SF3B1K700E) mutation is strongly associated with tumor growth in pancreatic ductal adenocarcinoma (PDAC). Knockdown of SF3B1 significantly retarded cell proliferation and tumor growth in a cell line (Panc05.04) with the SF3B1K700E mutation. However, SF3B1 knockdown had no notable effect on cell proliferation in two cell lines (BxPC3 and AsPC1) carrying wild‐type SF3B1. Ectopic expression of SF3B1K700E but not SF3B1WT in SF3B1‐knockout Panc05.04 cells largely restored the inhibitory role induced by SF3B1 knockdown. Introduction of the SF3B1K700E mutation in BxPC3 and AsPC1 cells also boosted cell proliferation. Gene set enrichment analysis demonstrated a close correlation between SF3B1 mutation and aerobic glycolysis. Functional analyses showed that the SF3B1K700E mutation promoted tumor glycolysis, as evidenced by glucose consumption, lactate release, and extracellular acidification rate. Mechanistically, the SF3B1 mutation promoted the aberrant splicing of PPP2R5A and led to the activation of the glycolytic regulator c‐Myc via post‐translational regulation. Pharmacological activation of PP2A with FTY‐720 markedly compromised the growth advantage induced by the SF3B1K700E mutation in vitro and in vivo. Taken together, our data suggest a novel function for SF3B1 mutation in the Warburg effect, and this finding may offer a potential therapeutic strategy against PDAC with the SF3B1K700E mutation.

Background: Biometric parameters play an important role in studies on myopia. This study aimed to explore the application of a commercially available two-dimensional visualized swept-source optical coherence tomography (OCT) system, for in vivo biometric measurement in multiple myopia model species. Methods: In this study, chickens, guinea pigs, and C57BL/6 mice underwent eye imaging with the commercially available OCT (CASIA2), and the original images were used to calculate the central corneal thickness, anterior chamber depth (ACD), lens thickness (LT), vitreous chamber depth (VCD), and axial length (AL). The retinal thickness and choroidal thickness were also calculated in chicken eyes. The repeatability of the biometric measurement outcomes was analyzed. Results: Excellent repeatable AL measurements were obtained for all three species, with an intraclass correlation coefficient (ICC) of ≥0.941 and a within-subject standard deviation of ≤0.055. Excellent repeatability was found in chicken eyes for ACD, LT, and VCD, with an ICC of ≥0.932; in guinea pig eyes for ACD and VCD, with an ICC of ≥0.934; and in mouse eyes for LT, with an ICC of ≥0.941. Conclusions: It is effective to use commercially available OCT to measure biometric parameters in chickens, guinea pigs, and C57BL/6 mice. This methodology could potentially increase the accuracy and efficiency of future myopia animal experiments.

Purpose: To develop predictive models for the intraocular pressure (IOP) of patients undergoing small incision lenticule extraction (SMILE) procedures, measured with a noncontact tonometer (NCT), Goldmann applanation tonometry (GAT), and an ocular response analyzer (ORA).Methods: In this prospective study, a total of 104 eyes (−6.23 ± 2.06 diopters) of 52 patients (24.38 ± 4.76 years) undergoing SMILE procedures were included. The intraocular pressure was measured (IOPNCT with NCT, IOPGAT with GAT, and IOPcc and IOPg with ORA) before surgery and at postoperative 6 months. Information on age, preoperative and attempted spherical equivalent (SE), ablation depth, preoperative values and postoperative changes in central corneal thickness (CCT), K1, K2, Km, corneal hysteresis (CH) and corneal resistance factor (CRF) values was collected in order to predict IOPs.Results: All surgeries were uneventful. At postoperative 6 months, the efficacy and safety index were 1.04 ± 0.15 and 1.08 ± 0.18, respectively. Significant decreases were detected in postoperative IOPNCT, IOPGAT, IOPcc, and IOPg compared to preoperative values (all p < 0.001). No relationship was found between any IOP and ablation depth, attempted SE, and preoperative SE, as well as CCTdifference (all p > 0.05). Predictive models for IOPs were constructed to predict preoperative values, and R2 values were 67.5% (IOPNCT), 64.5% (IOPGAT), 78.7% (IOPcc), and 82.0% (IOPg). The prediction band of IOPNCT and IOPGAT was 7.4–15.1 mmHg and 8–16 mmHg, respectively.Conclusion: Predictive models for IOP measurements after SMILE procedures can be helpful in clinical practice.

The incidence rate of human uterine leiomyomas is over 70% in the women of childbearing age, which has caused serious health and financial burden. Our previous study confirmed that Bisphenol A (BPA)，representative environmental estrogen, promoted the proliferation of human uterine leiomyomas and up-regulated the expression of cell proliferation-related genes. In this study, by combining ChIP-seq and RNA-seq, it was shown that after BPA intervention, H3K27ac modification levels and gene expression levels were altered in uterine leiomyomas cells. Moreover experimental verification found that BPA can regulate ITGA2 through the transcription factor XBP1, activate the downstream PI3K/AKT signaling pathway, eventually promote the proliferation of uterine leiomyomas. The present study provides new insights into the pathogenesis associated with exposure to BPA and other endocrine disruptors with similar effects by defining XBP1 as an important regulator, and which may act as an intervention and treatment target for uterine leiomyomas.

Objective This study aimed to establish a prognostic model related to prostate cancer (PCa) recurrence-free survival (RFS) and identify biomarkers. Methods The RFS prognostic model and key genes associated with PCa were established using Least Absolute Shrinkage and Selection Operator (LASSO) and Cox regression from the Cancer Genome Atlas (TCGA)-PRAD and the Gene Expression Omnibus (GEO) GSE46602 datasets. The weighted gene co-expression network (WGCNA) was used to analyze the obtained key modules and genes, and gene set enrichment analysis (GSEA) was performed. The phenotype and mechanism were verified in vitro. Results A total of 18 genes were obtained by LASSO regression, and an RFS model was established and verified (TCGA, AUC: 0.774; GSE70768, AUC: 0.759). Three key genes were obtained using multivariate Cox regression. WGCNA analysis obtained the blue module closely related to the Gleason score (cor = –0.22, P = 3.3e − 05) and the unique gene glutathione peroxidase 2 (GPX2). Immunohistochemical analysis showed that the expression of GPX2 was significantly higher in patients with PCa than in patients with benign prostatic hyperplasia (P

Tumor-initiating cells with reprogramming plasticity or stem-progenitor cell properties (stemness) are thought to be essential for cancer development and metastatic regeneration in many cancers; however, elucidation of the underlying molecular network and pathways remains demanding. Combining machine learning and experimental investigation, here we report CD81, a tetraspanin transmembrane protein known to be enriched in extracellular vesicles (EVs), as a newly identified driver of breast cancer stemness and metastasis. Using protein structure modeling and interface prediction-guided mutagenesis, we demonstrate that membrane CD81 interacts with CD44 through their extracellular regions in promoting tumor cell cluster formation and lung metastasis of triple negative breast cancer (TNBC) in human and mouse models. In-depth global and phosphoproteomic analyses of tumor cells deficient with CD81 or CD44 unveils endocytosis-related pathway alterations, leading to further identification of a quality-keeping role of CD44 and CD81 in EV secretion as well as in EV-associated stemness-promoting function. CD81 is coexpressed along with CD44 in human circulating tumor cells (CTCs) and enriched in clustered CTCs that promote cancer stemness and metastasis, supporting the clinical significance of CD81 in association with patient outcomes. Our study highlights machine learning as a powerful tool in facilitating the molecular understanding of new molecular targets in regulating stemness and metastasis of TNBC.

Bromine-rich lithium argyrodite electrolytes with high ionic conductivity and low cost are promising for the replacement of flammable liquid electrolytes and separators in lithium-ion batteries. However, the synthesis process of argyrodite electrolytes is usually complex and time-consuming. We use a facile solid-state reaction method to obtain a highly Li-ion conductive Li5.5PS4.5Br1.5 (LPSB). The influence of annealing temperature on the phase and ionic conductivity of the LPSB was investigated for the first time. High ionic conductivity of 5.21 × 10−3 S cm−1 at room temperature for the LPSB with minor LiBr impurity was achieved by direct annealing at 430°C for 8 h. The In/InLi | LPSB | LiCoO2@ LiNb0.5Ta0.5O3 (LCO(coated))-LPSB cell with 8.53 mg cm−2 LCO loading shows a discharge capacity of 102 mAh g−1 with high-capacity retention of 93% after 70 cycles at 0.5 mA cm−2 at 30°C.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly contagious disease that affects the global pig industry. To understand mechanisms of susceptibility/resistance to PRRSV, this study profiled the time-serial white blood cells transcriptomic and serum metabolomic responses to PRRSV in piglets from a crossbred population of PRRSV-resistant Tongcheng pigs and PRRSV-susceptible Large White pigs. Gene set enrichment analysis (GSEA) illustrated that PRRSV infection up-regulated the expression levels of marker genes of dendritic cells, monocytes and neutrophils and inflammatory response, but down-regulated T cells, B cells and NK cells markers. CIBERSORT analysis confirmed the higher T cells proportion in resistant pigs during PRRSV infection. Resistant pigs showed a significantly higher level of T cell activation and lower expression levels of monocyte surface signatures post infection than susceptible pigs, corresponding to more severe suppression of T cell immunity and inflammatory response in susceptible pigs. Differentially expressed genes between resistant/susceptible pigs during the course of infection were significantly enriched in oxidative stress, innate immunity and humoral immunity, cell cycle, biotic stimulated cellular response, wounding response and behavior related pathways. Fourteen of these genes were distributed in 5 different QTL regions associated with PRRSV-related traits. Chemokine CXCL10 levels post PRRSV infection were differentially expressed between resistant pigs and susceptible pigs and can be a promising marker for susceptibility/resistance to PRRSV. Furthermore, the metabolomics dataset indicated differences in amino acid pathways and lipid metabolism between pre-infection/post-infection and resistant/susceptible pigs. The majority of metabolites levels were also down-regulated after PRRSV infection and were significantly positively correlated to the expression levels of marker genes in adaptive immune response. The integration of transcriptome and metabolome revealed concerted molecular events triggered by the infection, notably involving inflammatory response, adaptive immunity and G protein-coupled receptor downstream signaling. This study has increased our knowledge of the immune response differences induced by PRRSV infection and susceptibility differences at the transcriptomic and metabolomic levels, providing the basis for the PRRSV resistance mechanism and effective PRRS control.

Detailed insight into the radiation-induced changes in tumor microvasculature is crucial to maximize the efficacy of radiotherapy against breast cancer. Recent advances in imaging have enabled precise targeting of solid lesions. However, intratumoral heterogeneity makes treatment planning and monitoring more challenging. Conventional imaging cannot provide high-resolution observation and longitudinal monitoring of large-scale microvascular in response to radiotherapy directly in deep tissues. Herein, we report on an emerging non-invasive imaging assessment method of morphological and functional tumor microvasculature responses with high spatio-temporal resolution by means of optoacoustic imaging (OAI). In vivo imaging of 4T1 breast tumor response to a conventional fractionated radiotherapy at varying dose (14 × 2 Gy and 3 × 8 Gy) has been performed after 2 weeks following treatment. Remarkably, optoacoustic images can generate richful contrast for the tumor microvascular architecture. Besides, the functional status of tumor microvasculature and tumor oxygenation levels were further estimated using OAI. The results revealed the differential (size-dependent) nature of vascular responses to radiation treatments at varying doses. The vessels exhibited an decrease in their density accompanied by a decline in the number of vascular segments following irradiation, compared to the control group. The measurements further revealed an increase of tumor oxygenation levels for 14 × 2 Gy and 3 × 8 Gy irradiations. Our results suggest that OAI could be used to assess the response to radiotherapy based on changes in the functional and morphological status of tumor microvasculature, which are closely linked to the intratumor microenvironment. OAI assessment of the tumor microenvironment such as oxygenation status has the potential to be applied to precise radiotherapy strategy.

Background/aimsNon-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide. Iron overload has been implicated in chronic non-communicable liver diseases, but its relationship with NAFLD remains unclear. This study aimed to investigate the underlying roles of iron overload in the development of NAFLD.MethodsMale Sprague Dawley rats were fed with a high-fat diet (HFD) and/or iron for 8, 12, and 20 weeks. Some rats fed with HFD plus iron also received intraperitoneal injection of deferoxamine (DFO) for 8 weeks. Liver steatosis, lipid metabolism and injury were evaluated.ResultsA NAFLD model, including typical liver steatosis, was established by feeding rats with a HFD, while iron overload alone is not enough to induce severe NAFL. Compared with rats fed a HFD, excess iron further increased lipid accumulation, serum levels of lipids, enzymes of liver function, and expression levels of CD36 and FAS in rat liver. In addition, iron overload decreased the activities of antioxidative enzymes in liver compared with HFD rats. The levels of CPT1 and the ratios of p-ACC/ACC were also decreased by iron overload. DFO effectively reversed the abnormal lipid metabolism and liver damage induced by a high-fat, high-iron diet.ConclusionA HFD plus iron overload might synergistically aggravate lipid metabolism disorders, liver injury, and oxidative damage, compared with a HFD alone. DFO might help to alleviate lipid metabolism dysfunction and improve the pathogenesis of NAFLD.

Abstract Background To assess the effects of warm compress (WC) on tear film lipid layer, blink pattern and Meibomian gland function in patients with dry eye following femtosecond laser small incision lenticule extraction (SMILE) and laser-assisted subepithelial keratomileusis (LASEK). Methods We enrolled 37 eyes of 37 participants, each with dry eye for more than 2 years following SMILE (25 eyes) or LASEK (12 eyes). WC was performed using a spontaneously heating eye mask. Tear film break-up time (TBUT), tear film lipid layer thickness (TFLLT), blink pattern, Meibomian secretory function scores (MGS), visual acuity, spherical equivalent (SE), keratometry, central corneal thickness (CCT) and aberration were assessed before and after WC. Results After WC, the following mean values all increased relative to baselines: CCT, SE, minimum (Min-), maximum (Max-) and average (Ave-) TFLLT, TBUT, total MGS (TMGS), number of glands secreting any liquid (MGL), and complete blink rate (CBR) (p values ranging from

Abstract Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide. In adults with NAFLD, fibrosis can develop and progress to liver cirrhosis and liver failure. However, the underlying molecular mechanisms of fibrosis progression are not fully understood. Using total RNA-Seq, we investigated the molecular mechanisms of NAFLD and fibrosis. We sequenced liver tissue from 143 adults across the full spectrum of fibrosis stage including those with stage 4 fibrosis (cirrhosis). We identified gene expression clusters that strongly correlate with fibrosis stage including four genes that have been found consistently across previously published transcriptomic studies on NASH i.e. COL1A2, EFEMP2, FBLN5 and THBS2. Using cell type deconvolution, we estimated the loss of hepatocytes versus gain of hepatic stellate cells, macrophages and cholangiocytes with advancing fibrosis stage. Hepatocyte-specific functional analysis indicated increase of pro-apoptotic pathways and markers of bipotent hepatocyte/cholangiocyte precursors. Regression modelling was used to derive predictors of fibrosis stage. This study elucidated molecular and cell composition changes associated with increasing fibrosis stage in NAFLD and defined informative gene signatures for the disease.

Abstract Ultrasound-guided axillary brachial plexus block is increasingly used in preschool-age patients. However, the minimum effective volume of local anaesthetics has not been determined. With ethical committee approval and written informed consent from the guardians of all paediatric patients, we studied 27 consecutive patients aged 3 to 6 years who were scheduled for hand surgery. After general anaesthesia, eligible patients received a set volume of ultrasound-guided axillary brachial plexus block. We determined the volume of 0.2% ropivacaine for consecutive patients from the preceding patient’s outcome. The initial volume was 0.4 ml/kg. The testing interval was set at 0.05 ml/kg, and the lowest volume was 0.1 ml/kg. The following conditions were defined as a successful block: no heart rate changes, body movement, or ventilatory disorders during the operation; no use of fentanyl in the PACU; and a postoperative sensory block score

Circulating tumor cell (CTC) clusters are more efficient at mediating metastasis as compared to single cells and are associated with poor prognosis in breast cancer. Here, the authors show that ICAM1 is enriched in CTC clusters and its loss suppresses cell-cell interaction and CTC cluster formation, and propose ICAM1 as a therapeutic target for treating breast cancer metastasis.

Abstract Glioblastoma multiforme (GBM) is an extremely aggressive brain tumor for which new therapeutic approaches are urgently required. Unfolded protein response (UPR) plays an important role in the progression of GBM and is a promising target for developing novel therapeutic interventions. We identified ubiquitin-activating enzyme 1 (UBA1) inhibitor TAK-243 that can strongly induce UPR in GBM cells. In this study, we evaluated the functional activity and mechanism of TAK-243 in preclinical models of GBM. TAK-243 significantly inhibited the survival, proliferation, and colony formation of GBM cell lines and primary GBM cells. It also revealed a significant anti-tumor effect on a GBM PDX animal model and prolonged the survival time of tumor-bearing mice. Notably, TAK-243 more effectively inhibited the survival and self-renewal ability of glioblastoma stem cells (GSCs) than GBM cells. Importantly, we found that the expression level of GRP78 is a key factor in determining the sensitivity of differentiated GBM cells or GSCs to TAK-243. Mechanistically, UBA1 inhibition disrupts global protein ubiquitination in GBM cells, thereby inducing ER stress and UPR. UPR activates the PERK/ATF4 and IRE1α/XBP signaling axes. These findings indicate that UBA1 inhibition could be an attractive strategy that may be potentially used in the treatment of patients with GBM, and GRP78 can be used as a molecular marker for personalized treatment by targeting UBA1.

Abstract The ongoing coronavirus disease-2019 (COVID-19) pandemic, caused by a novel coronavirus termed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that is closely related to SARS-CoV, poses a grave threat to global health and has devastated societies worldwide. One puzzling aspect of COVID-19 is the impressive variation in disease manifestations among infected individuals, from a majority who are asymptomatic or exhibit mild symptoms to a smaller, largely age-dependent fraction who develop life-threatening conditions. Some of these differences are likely the consequence of host genetic factors. Systems genetics using diverse and replicable cohorts of isogenic mice represents a powerful way to dissect those host genetic differences that modulate microbial infections. Here we report that the two founders of the large BXD family of mice—C57BL/6J and DBA/2J, differ substantially in their susceptibility to a mouse-adapted SARS-CoV, MA15. Following intranasal viral challenge, DBA/2J develops a more severe disease than C57BL/6J as evidenced by more pronounced and sustained weight loss. Disease was accompanied by high levels of pulmonary viral replication in both strains early after infection but substantially delayed viral clearance in DBA/2J. Our data reveal that the parents of the BXD family are segregated by clear phenotypic differences during MA15 infection and support the feasibility of using this family to systemically dissect the complex virus-host interactions that modulate disease progression and outcome of infection with SARS-CoV, and provisionally also with SARS-CoV-2.

Abstract Addressing microstructure-property relations of polymer nanocomposites is vital for designing advanced dielectrics for electrostatic energy storage. Here, we develop an integrated phase-field model to simulate the dielectric response, charge transport, and breakdown process of polymer nanocomposites. Subsequently, based on 6615 high-throughput calculation results, a machine learning strategy is schemed to evaluate the capability of energy storage. We find that parallel perovskite nanosheets prefer to block and then drive charges to migrate along with the interfaces in x-y plane, which could significantly improve the breakdown strength of polymer nanocomposites. To verify our predictions, we fabricate a polymer nanocomposite P(VDF-HFP)/Ca2Nb3O10, whose highest discharged energy density almost doubles to 35.9 J cm−3 compared with the pristine polymer, mainly benefit from the improved breakdown strength of 853 MV m−1. This work opens a horizon to exploit the great potential of 2D perovskite nanosheets for a wide range of applications of flexible dielectrics with the requirement of high voltage endurance.

Abstract The alterations in the gut microbiota have been reported to be correlated with the development of depression. The purpose of this study was to investigate the changes of intestinal microbiota in depressed patients after antidepressant treatment. We recruited 30 MDD patients (MDD group) and 30 healthy controls (control group). The MDD group received individualized treatment with escitalopram at a maximum dose of 20 mg/day. After depressive symptoms improved to a HAMD scale score > 50%, a fecal sample was collected again and used as the follow-up group. The differences of gut microbiota between patients and controls, the characteristics of gut microbiota under treatment and the potential differences in metabolic functions were thus investigated. The Firmicutes/Bacteroidetes ratio was significantly different within three groups, and the ratio of follow-up group was significantly lower than those of the other two groups. Alpha diversity was significantly higher in MDD group than those of the other groups, and the alpha diversity was not significantly different between control and follow-up groups. The beta diversity of some patients resembled participants in the control group. The metabolic function of gut microbiota after treatment was still different from that of the control group. This study suggests that the intestinal flora of depressed patients has a tendency to return to normal under escitalopram treatment.

ObjectiveTo study the efficacy of interval debulking surgery (IDS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) compared to IDS alone for the treatment of ovarian cancer after neoadjuvant chemotherapy (NACT).MethodsWe conducted a retrospective study of patients with stage IIIC/IV high-grade serous ovarian carcinoma who underwent surgery at our center from January 2018 to December 2019. Patients who underwent IDS after NACT with (N = 20) or without (N = 42) HIPEC were included. HIPEC was administered after surgery and was combined with 1–2 courses of intraperitoneal hyperthermic perfusion with normal saline only. We analyzed clinical information and outcomes for the two groups.ResultsThe median progression-free survival (PFS) was 14.05 months in the IDS plus HIPEC group and 12.97 months in the IDS group (P = 0.597). The median overall survival (OS) was not reached. After adjustment for age between the two groups, the differences in PFS and OS remained nonsignificant. The change ratio of postoperative CA-125 to preoperative CA-125 was 0.66 in the IDS plus HIPEC group and 0.53 in the IDS group (P = 0.341). The difference in human epididymis protein 4 (HE-4) change ratio between the two groups was nonsignificant (P = 0.225). No significant difference was observed in the occurrence of grade 3 and 4 adverse events between the two groups (P = 0.201).ConclusionAfter NACT, IDS plus HIPEC did not show significant PFS and tumor index change ratio benefits over IDS alone in patients with primary ovarian cancer. Further investigations are needed to assess the role of HIPEC in the treatment of ovarian cancer.

PurposeTo investigate long-term trends in corneal densitometry and associated influencing factors following small incision lenticule extraction (SMILE).MethodsA comparative study was performed among 72 eyes of 38 patients undergoing SMILE. Eyes were divided into moderate myopia [mean spherical equivalent (SE),−4.22 ± 0.68D] and high myopia (mean SE,−7.63 ± 1.09 D) groups. Visual acuity, manifest refraction, corneal topography and corneal densitometry (CD) were evaluated preoperatively and 3 years postoperatively.ResultsThe efficacy indices at last postoperative follow-up (42.47 ± 0.51 months) were 0.92 ± 0.21 and 0.97 ± 0.22, the safety indices were 1.12 ± 0.17 and 1.14 ± 0.21 for high and moderate myopia, respectively (all P > 0.05). CD values in the 0–6 mm zone of the posterior corneal layer was statistically significantly lower than the preoperative values in both groups. Postoperative CD values (0–2 mm zone) in the posterior layer of the high myopia group were statistically significantly lower than in the moderate myopia group (P = 0.025); CD values (2–6 mm zone) in the anterior layer were higher in the high myopia group (P = 0.026). Correlation analyses showed that CD values in the 0–2 mm middle layer were negatively correlated with lenticule thickness in high myopia (r = −0.411, P = 0.016); there was a negative correlation between the CD values (0–6 mm) and corneal oblique trefoil in this group (P < 0.05).ConclusionCorneal transparency in the 0–6 mm zone of the posterior cornea increased following SMILE in moderate and high myopia. Long-term CD values in high myopia may be correlated with oblique trefoil and lenticule thickness.

In the airway, IgE is traditionally regarded as a key mediator in allergic diseases, such as AR and allergic asthma. However, growing evidence demonstrates the importance of local IgE in airway inflammatory diseases, irrespective of the presence of allergy. In this review, we discuss the most recent evidence for IgE in chronic rhinosinusitis with nasal polyps(CRSwNP), including the local IgE’s characteristics, the modulation of its synthesis, and its function. The levels of local IgE are significantly elevated in polyps independently of IgE serum levels and atopic status. Local IgE, which is correlated with type 2 inflammation, is polyclonal and functional. IgE is produced by active B cells and is dependent on the class switch recombination(CSR). In NPs, this process is triggered by not only allergens but also microbial colonization, especially the superantigen- Staphylococcus aureus. The production of local IgE is modulated by lymphocytes(such as Tfh, ILC2s, iTreg), cytokines(such as IL-4, IL-13, IFN-γ, TGF-β, IL-2, IL-21), transcription factors, and B cell-intrinsic factor. Due to the central role of IgE in NPs, it is regarded as an ideal target for therapy and has been proved to be clinically successful. Based on this knowledge, we believe that exploring the trigger and regulatory factors for the activation of local B cells and CSR to IgE will provide more valuable information for us to recognize the pathological mechanisms of local IgE and offer the possible option for new therapeutic targets of nasal polyps.

PurposeTo analyze the development process of small incision lenticule extraction (SMILE) surgery in a 12-year period.MethodsWe conducted a literature search for SMILE research from 2011 to 2022 using the Science Citation Index Expanded (SCIE) of the Web of Science Core Collection (WoSCC). The VOS viewer, and CiteSpace software were used to perform the bibliometric analysis. Publication language, annual growth trend, countries/regions and institutions, journals, keywords, references, and citation bursts were analyzed.ResultsA total of 731 publications from 2011 to 2022 were retrieved. Annual publication records grew from two to more than 100 during this period. China had the highest number of publications (n = 326). Sixty-five keywords that appeared more than four times were classified into six clusters: femtosecond laser technology, dry eye, biomechanics, visual quality, complications, and hyperopia.ConclusionThe number of literatures has been growing rapidly in the past 12 years. Our study provides a deep insight into publications on SMILE for researchers and clinicians with bibliometric analysis for the first time.

ZnO/Graphene (G)/Graphene Oxide (GO)/Multi-walled Carbon Nanotube (MCNT) composite aerogels with a three-dimensional porous structure were prepared by the sol-gel method under average temperature and alkaline conditions, combined with freeze-drying process and heat treatment process. The photocatalytic degradation of Rhodamine B (RhB) was mainly studied. The scanning electron microscope (SEM) test results showed that the morphology uniformity of the ZnO/G/GO/MCNT composite aerogel was significantly enhanced, which effectively solving the agglomeration problem of MCNT and ZnO. The photocatalytic degradation test results of RhB show that due to the synergistic effect of physical adsorption and photocatalytic degradation, the total degradation efficiency of RhB by ZnO/G/GO/MCNT could reach 86.8%, which is 3.3 times higher than that of ZnO. In addition, the synergistic effect of ZnO and G effectively hinders the recombination of photo-generated electron-hole pairs and enhances photocatalytic activity. The ZnO/G/GO/MCNT composite aerogel can be applied in the visible light catalytic degradation of water pollution.

Breast cancer metastases to the bone can lead to a series of bone-related events that seriously affect the quality of life. Pexmetinib, a novel p38 mitogen-activated protein kinase (p38) inhibitor that has been evaluated in phase I clinical trials for myelodysplastic syndrome, but the effects of Pexmetinib on breast cancer induced osteolysis haven’t been explored. Here, we found that Pexmetinib inhibited receptor activator of nuclear factor-κB ligand-induced osteoclast formation and bone resorption in vitro. Pexmetinib suppressed p38-mediated signal transducer and activator of transcription 3 (STAT3), which direct regulated transcription of the nuclear factor of activated T cells 1 (NFATc1), leading to reduced osteoclast formation. Moreover, Pexmetinib exerted anti-tumor effects in breast cancer cells in vitro via suppressing p38-mediated STAT3 activation and matrix metalloproteinases (MMPs) expression. Furthermore, Pexmetinib suppressed breast cancer-associated osteolysis in vivo. These results suggest that Pexmetinib may be a promising drug for the treatment of breast cancer-induced osteolysis.

Thrombotic complications pose serious health risks worldwide. A significant change in our understanding of the pathophysiology of thrombosis has occurred since the discovery of extracellular traps (ETs) and their prothrombotic properties. As a result of immune cells decondensing chromatin into extracellular fibers, ETs promote thrombus formation by acting as a scaffold that activates platelets and coagulates them. The involvement of ETs in thrombosis has been reported in various thrombotic conditions including deep vein thrombosis (DVT), pulmonary emboli, acute myocardial infarction, aucte ischemic stroke, and abdominal aortic aneurysms. This review summarizes the existing evidence of ETs in human and animal model thrombi. The authors described studies showing the existence of ETs in venous or arterial thrombi. In addition, we studied potential novel therapeutic opportunities related to the resolution or prevention of thrombosis by targeting ETs.

Lactic acid bacteria (LAB) have already been used as fermentation strains to enhance the antioxidant capacity of polyphenols. Antioxidant capacity is one of the most important factors to inhibit advanced glycation end product (AGE) formation and could LAB increase the inhibitory capacity of procyanidins on AGEs formation? It was surprising that opposite results were obtained both in simulated food processing and gastrointestinal digestion systems. After incubation with Lactobacillus plantarum (L. plantarum), litchi pericarp oligomeric procyanidins (LPOPCs) were bioconverted to several phenolic acids, which increased the antioxidant activity as expected. However, antiglycation ability and trapping carbonyl compounds capacity both weakened and it might be the primary reason for decreasing the inhibitory effect on AGE formation. Furthermore, it was found that LPOPCs incubated with L. plantarum inhibited the activity of digestive enzymes and thus decreased the digestibility of glycated protein. Our study systematically proposed for the first time that procyanidins bioconversion is an effective means to improve the antioxidant activity but has no remarkable promoting effect on AGEs inhibition.

Magnesium (Mg)-based materials are considered as potential materials for biodegradable vascular stents, and some Mg-based stents have obtained regulatory approval. However, the development and application of Mg-based stents are still restricted by the rapid degradation rate of Mg and its alloys. In order to screen out the desirable Mg-based materials for stents, the degradation behavior still needs further systematic study, especially the degradation behavior under the action of near-physiological fluid. Currently, the commonly used Mg-based vascular stent materials include pure Mg, AZ31, and WE43. In this study, we systematically evaluated their corrosion behaviors in a dynamic environment and studied the effect of their degradation products on the behavior of vascular cells. The results revealed that the corrosion rate of different Mg-based materials was related to the composition of the elements. The dynamic environment accelerated the corrosion of Mg-based materials. All the same, AZ31 still shows good corrosion resistance. The effect of corrosive products on vascular cells was beneficial to re-endothelialization and inhibition of smooth muscle cell proliferation at the implantation site of vascular stent materials.

Cancer-associated fibroblasts (CAFs) are a major contributor to tumor stromal crosstalk in the tumor microenvironment (TME) and boost tumor progression by promoting angiogenesis and lymphangiogenesis. This study aimed to identify prognostic genes associated with CAFs that lead to high morbidity and mortality in ovarian cancer (OC) patients. We performed bioinformatics analysis in 16 multicenter studies (2,742 patients) and identified CAF-associated hub genes using the weighted gene co-expression network analysis (WGCNA). A machine learning methodology was used to identify COL16A1, COL5A2, GREM1, LUM, SRPX, and TIMP3 and construct a prognostic signature. Subsequently, a series of bioinformatics algorithms indicated risk stratification based on the above signature, suggesting that high-risk patients have a worse prognosis, weaker immune response, and lower tumor mutational burden (TMB) status but may be more sensitive to routine chemotherapeutic agents. Finally, we characterized prognostic markers using cell lines, immunohistochemistry, and single-cell sequencing. In conclusion, these results suggest that the CAF-related signature may be a novel pretreatment guide for anti-CAFs, and prognostic markers in CAFs may be potential therapeutic targets to inhibit OC progression.