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Abstract Acupuncture is an important alternative therapy in treating major depressive disorder (MDD), but its efficacy and safety are still not well assessed. This study is the first network meta-analysis exploring the effectiveness and safety of acupuncture, common pharmacological treatments or other non-medication therapies for MDD. Eight databases including PubMed, Embase, Allied and Complementary Medicine Database, Cochrane Library, Wan Fang Data, China National Knowledge Infrastructure, China Biology Medicine disc, and Chongqing VIP Database were searched up to Jan 17, 2021. Articles were screened and selected by two reviewers independently. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the certainty of the evidence. A total of 71 eligible studies were included. The network analysis results indicated that the combined interventions of electro-acupuncture (EA) with selective serotonin reuptake inhibitors (SSRIs) and manual acupuncture (MA) with SSRIs were more effective in improving depression symptoms compared with acupuncture alone, pharmacological interventions alone, or other inactive groups. Among all the regimens, EA with SSRIs was found to have the highest effect in improving depression symptoms of MDD. In addition, there were slight differences in the estimations of the various treatment durations. The combination of acupuncture and serotonin-norepinephrine reuptake inhibitors (SNRIs) was found to be more effective than SNRIs alone. In conclusion, acupuncture and its combinations could be safe and effective interventions for MDD patients. EA with SSRIs seems to be the most effective intervention among the assessed interventions. Well-designed and large-scale studies with long-term follow-up should be conducted in the future.

Serum lipids have been associated with an increased risk of various cardiovascular diseases (CVDs) in several observational studies, but the causal inference between the remnant cholesterol (RC) levels and several CVDs risk has not been established. The purpose of this study was to investigate whether there is a causal relationship between RC levels and risk of developing CVDs by a bidirectional two-sample Mendelian randomization (TSMR) analysis. One TSMR analysis was performed using the publicly released large-scale genome-wide association study (GWAS) data. Inverse variance weighted (IVW) method was chosen as the main analysis method, and MR-Egger, weighted median, simple mode, and weighted mode were used as supplementary methods. We conducted a series of sensitivity analyses to assess the robustness of the main results, including the Cochran's Q test, MR-Egger intercept test, leave-one-out sensitivity analysis, and funnel plot. The main IVW method revealed that genetically predicted serum level of RC is significantly associated with an increased risk of developing ischemic heart disease (OR = 1.409, 95%CI = 1.284-1.546, P value = 4.753E-13), unstable angina pectoris (OR = 1.621, 95%CI = 1.398-1.880, P value = 1.672E-10), myocardial infarction (OR = 1.526, 95%CI = 1.337-1.741, P value = 3.771E-10), cardiac arrest (OR = 1.595, 95%CI = 1.322-1.924, P value = 1.076E-06), heart failure (OR = 1.086, 95%CI = 1.009-1.169, P value = 0.028), hypertension (OR = 1.089, 95%CI = 1.043-1.136, P value = 9.458E-05), major coronary heart disease (CHD) events (OR = 1.515, 95%CI = 1.376-1.669, P value = 3.217E-17), coronary atherosclerosis (OR = 1.388, 95%CI = 1.231-1.564, P value = 7.739E-08), cardiac arrhythmias (OR = 1.067, 95%CI = 1.008-1.130, P value = 0.025), and atrial fibrillation and flutter (OR = 1.122, 95%CI = 1.039-1.211, P value = 0.003). Additionally, the causal associations between the RC levels and these CVDs remained significant after correcting for the false discovery rate (all P value < 0.05). However, this study did not find any significant association of RC with cardiomyopathy and pericarditis (both P value > 0.05). Heterogeneity existed in the IVs of RC and ischemic heart disease, unstable angina pectoris, myocardial infarction, heart failure, hypertension, major CHD events, cardiomyopathy, coronary atherosclerosis, cardiac arrhythmias and atrial fibrillation and flutter using the Cochran's Q test (all P value < 0.05). Moreover, there was no horizontal pleiotropy in this study (all P value > 0.05). The leave-one-out sensitivity analyses showed that the causal effects between RC level and CVDs (except for heart failure, cardiomyopathy, pericarditis and cardiac arrhythmias) are not driven by a single SNP. The funnel plots showed that there is no obvious potential bias in our study. In the replication analysis, the genetically predicted RC levels were positively associated with a 43.12% higher risk of coronary artery disease. This present study supported the causal link between RC and heightened the risk of CVDs, indicating that RC-lowering treatment might be effective in preventing CVDs., (© 2024. The Author(s).)

Silk fabrics hold immense historical value as precious legacies left by our ancestors, yet they face significant damage during archaeological excavations, necessitating urgent protective measures. However, The current protective materials can't effectively prevent the degradation of silk fabrics. Nanotechnology has emerged as a promising avenue for the consolidation and preservation of silk fabrics, offering novel concepts and materials. In this study, we propose an innovative and cost-effective method that uses the MOF-818 with a radical scavenging ability to enhance the protection of silk fabrics. The resulting demonstrates that the MOF-818 was the large surface area and porous properties, which exhibited excellent superoxide dismutase (SOD)-like activity at 10 ug/mL. The silk fabrics treated by MOF-818 displays small color difference, reduced the oxidation of functional group and prevents the degradation of silk fabrics. The successful development of this nanocomposite marks a significant advancement in silk protection, opening new horizons for the preservation of silk cultural relics., (© 2024. The Author(s).)

Observational studies have suggested the potential benefits of several medications for Parkinson's disease (PD) and their potential for repurposing. However, the conclusions drawn from these studies are not entirely consistent. To address this inconsistency, we used the two-sample Mendelian randomization (MR) method to explore the putative causal relationships between 23 medications and the risk and progression of PD. We applied inverse-variance weighted meta-analysis (IVW) to combine MR estimates. Additionally, sensitivity analyses were conducted to evaluate the robustness of the results. Our genetic evidence suggests that thyroid preparations and calcium channel blockers reduce the risk of PD, and salicylic acid and derivatives slow the progression of PD motor symptoms. Additionally, genetic evidence also suggests that four medications were associated with PD risk or progression, but the sensitivity analysis revealed that three of the medications may have interference caused by reverse causality. Our findings suggest that there are weak causal relationships between several medications and the risk or progression of PD. Though further replication studies are needed to verify these findings, these new insights may help in understanding the etiology of the disease, generate new clues related to drug discovery, and quantify the risk of future drug intake., (© 2024. The Author(s).)

Glycosylated haemoglobin index (HGI) has been shown to correlate with the prognosis of metabolic diseases, but the relationship with mortality remains unclear. This study included 18,285 US adults who participated in the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2018. During the median follow-up period of 115 months, a total of 2572 all-cause deaths and 671 cardiovascular disease (CVD) deaths occurred. The restricted cubic spline revealed a U-shaped correlation between HGI and all-cause and CVD mortality. After adjusting for all covariates, the optimal inflection point values in all-cause and CVD deaths were 0.17 and 0.02, respectively. In the left side of the inflection point, the risk of all-cause mortality and CVD mortality decreased by approximately 24% (HR 0.76, 95% CI 0.69, 0.84) and 25% (HR 0.75, 95% CI 0.60, 0.96) with the increase in HGI. Conversely, in the right of the inflection point, an increase of 1 unit in the HGI was linked with a 17% (HR 1.17, 95% CI 1.07, 1.27) and 31% (HR 1.31, 95% CI 1.15, 1.49) increase in all-cause and CVD mortality. Our study showed that HGI is an important tool for predicting the risk of all-cause mortality and CVD death in US adults and there is a U-shaped relationship between HGI and mortality., (© 2024. The Author(s).)

Particle geometric is a key parameter that defines the eometric attributes of calcareous sand particles and is intricately related to their mechanical traits, such as compression and shear. The scanning electron microscopy and digital imaging were applied to capture the microscopic properties and geometric projections of calcareous sand. The qualitative analysis, conventional statistical methods and fractal theory were employed to describe the geometric morphology of sand particles. Additionally, we analyzed the structural and physical traits of calcareous sand based on its unique biological genesis. We developed a hypothetical structural-physical model for calcareous sand. Our findings revealed the interwoven reticulation on the surface of calcareous gravel particles, along with an uneven distribution of pores on the external surface. As the particle size increased, the global profile factor decreased and the angularity increased. The critical threshold for the variations in flatness, surface roughness, and circularity was observed at a particle size of 5 mm, with the particle size having a relatively minor effect on these characteristics for particles smaller than 5 mm. The shape of the calcareous sand particles exhibited fractal characteristics, with fractal dimension serving as a measure of surface smoothness, particle breakage, and strength. These experimental results could significantly enhance our understanding of the mechanical behavior of calcareous sand., (© 2024. The Author(s).)

This study aims to address the issue of high energy consumption in the hydrocyclone separation process. By introducing a novel slotted overflow pipe structure and utilizing experimental and response surface optimization methods, the optimal parameters were determined. The research results indicate that the number of slots, slot angles, and positioning dimensions significantly influence the performance of the hydrocyclone separator. The optimal combination was found to be three layers of slots, a positioning dimension of 5.3 mm, and a slot angle of 58°. In a Φ100mm hydrocyclone separator, validated through multiple experiments, the separation efficiency increased by 0.26% and the pressure drop reduced by 24.88% under a flow rate of 900 ml/s. CFD simulation verified the reduction in internal flow field velocity and pressure drop due to the slotted structure. Therefore, this study provides an effective reference for designing efficient and low-energy hydrocyclone separators., (© 2024. The Author(s).)

Named entity recognition (NER) plays a crucial role in the extraction and utilization of knowledge of ancient Chinese books. However, the challenges of ancient Chinese NER not only originate from linguistic features such as the use of single characters and short sentences but are also exacerbated by the scarcity of training data. These factors together limit the capability of deep learning models, like BERT-CRF, in capturing the semantic representation of ancient Chinese characters. In this paper, we explore the semantic enhancement of NER in ancient Chinese books through the utilization of external knowledge. We propose a novel model based on Graph Neural Networks that integrates two different forms of external knowledge: dictionary-level and chapter-level information. Through the Graph Attention Mechanism (GAT), these external knowledge are effectively incorporated into the model's input context. Our model is evaluated on the C&#95;CLUE dataset, showing an improvement of 3.82% over the baseline BAC-CRF model. It also achieves the best score compared to several state-of-the-art dictionary-augmented models., (© 2024. The Author(s).)

The endothelial glycocalyx is damaged in postcardiac arrest syndrome (PCAS), but the prognostic value is unknown. We aimed to observe the expression and prognostic value of glycocalyx shedding products, including syndecan-1 (SDC-1), hyaluronan (HA), and heparan sulfate (HS) in PCAS. Data on clinical and 28-day outcomes of seventy-one consecutive patients with out-of-hospital cardiac arrest (OHCA) after the return of spontaneous circulation (ROSC) were collected. SDC-1, HA, and HS were measured on days 0, 1, and 3 after ROSC. Thirty healthy individuals were controls. Glycocalyx shedding was observed in human umbilical vein endothelial cells (HUVECs) stimulated during hypoxia and reoxygenation in vitro. Within 4 h of ROSC, SDC-1 and HA levels, significantly increased. In the 28-day non-survivors, HA levels showed a gradual upward trend, SDC-1 remained at a high level, and HS levels first increased, then decreased. Kaplan-Meier curves and binary logistic regression analysis showed the prognostic value of SDC-1 levels on days 0, 1, and 3, HA levels on days 1 and 3, and HS levels on day 1. Only HS levels on day 1 showed a prognostic value for 28-day neurological outcomes. SDC-1 and HA levels were positively correlated with the no-flow time. In vitro, HUVECs showed shedding of SDC-1 and HS during a prolonged duration of hypoxia. After ROSC, SDC-1, HA, and HS levels may predict the 28-day survival after PCAS, and HS levels are associated with functional outcomes., (© 2024. The Author(s).)

The purpose of this work is to explore the properties of the lignin-derived amine-free photoinitiating systems (PISs) during the curing process. Four novel hydrogen donors (HD1, HD2, HD3, and HD4) derived from lignin α-O-4 structural were designed and synthesized by simple methods, and their low C-H bond dissociation energies on methylene were determined by molecular orbitals theory. Four experimental groups using CQ (camphorquinone)/HD PIs formulated with Bis-GMA/TEGDMA (70 w%/30 w%) were compared to CQ/EDB (ethyl 4-dimethylamino benzoate) system. The photopolymerization profiles and double bond conversion rate was tracked by FTIR experiments; the color bleaching ability of the samples and color aging test assay were performed using color indexes measurements; The cytotoxicity of the samples was also compared to EDB related systems. All of the experimental groups with new HDs were compared to the control group with EDB by statistical analysis. Compared to CQ/EDB system, new lignin-derived hydrogen donors combined with CQ showed comparable or even better performances in polymerization initiation to form resin samples, under a blue dental LED in air. Excellent color bleaching property was observed with the new HDs. Aging tests and cytotoxicity examination of the resin were performed, indicating the new lignin compounds to be efficient hydrogen donors for amine-free CQ-based photo-initiating system. Novel lignin α-O-4 derived hydrogen donors are promising for further usage in light-curing materials., (© 2024. The Author(s).)

Jinlida granule (JLD) is a Traditional Chinese Medicine (TCM) formula used for the treatment of type 2 diabetes mellitus (T2DM). However, the mechanism of JLD treatment for T2DM is not fully revealed. In this study, we explored the mechanism of JLD against T2DM by an integrative pharmacology strategy. Active components and corresponding targets were retrieved from Traditional Chinese Medicine System Pharmacology (TCMSP), SwissADME and Bioinformatics Analysis Tool for Molecular Mechanisms of Traditional Chinese Medicine Database (BATMAN-TCM) database. T2DM-related targets were obtained from Drugbank and Genecards databases. The protein-protein interaction (PPI) network was constructed and analyzed with STRING (Search Toll for the Retrieval of Interacting Genes/proteins) and Cytoscape to get the key targets. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genomes (KEGG) enrichment analyses were performed with the Database for Annotation, Visualization and Integrated Discovery (DAVID). Lastly, the binding capacities and reliability between potential active components and the targets were verified with molecular docking and molecular dynamics simulation. In total, 185 active components and 337 targets of JLD were obtained. 317 targets overlapped with T2DM-related targets. RAC-alpha serine/threonine-protein kinase (AKT1), tumor necrosis factor (TNF), interleukin-6 (IL-6), cellular tumor antigen p53 (TP53), prostaglandin G/H synthase 2 (PTGS2), Caspase-3 (CASP3) and signal transducer and activator of transcription 3 (STAT3) were identified as seven key targets by the topological analysis of the PPI network. GO and KEGG enrichment analyses showed that the effects were primarily associated with gene expression, signal transduction, apoptosis and inflammation. The pathways were mainly enriched in PI3K-AKT signaling pathway and AGE-RAGE signaling pathway in diabetic complications. Molecular docking and molecular dynamics simulation verified the good binding affinity between the key components and targets. The predicted results may provide a theoretical basis for drug screening of JLD and a new insight for the therapeutic effect of JLD on T2DM., (© 2024. The Author(s).)

The particle breakage effect and compression characteristics of calcareous sand are related to the water content in the sand material. However, the effects of water content on the particle breakage and compression characteristics of calcareous sand have rarely been investigated. In this work, 50 sets of confined compression tests were conducted on calcareous sand specimens, and the compression characteristics and particle breakage effects of two single-particle-size groups (particle size ranges of 1-0.5 mm and 0.5-0.25 mm) of calcareous sand were investigated under five different water contents. The test results showed that with the increase in the water content, the final compression deformation of calcareous sand was positively correlated with the water content. The final compression deformation decreased when the water content reached a certain value. The water content corresponding to the peak final compression deformation was related to the gradation of the calcareous sand; the specific values were 10% and 15% for particle size ranges of 1-0.5 mm and 0.5-0.25 mm, respectively. With the increase in the water content, the slope of the loading curve of calcareous sand appeared to increase and then decrease, reaching maximum when the water content was 10%. Moreover, the slope of the loading curve was close to twice that of the loading curve of dry sand, whereas the slope of the unloading curve changed little. Under the same water content, the initial gradation had no effect on the compression and unloading characteristics of the specimens beyond a vertical pressure of 1 MPa. The effects of the variation in the water content on the particle breakage of calcareous sand were mainly reflected in the softening effect of water on the specimen particles, which reduced the Mohr strength of the particles., (© 2024. The Author(s).)

DNA damage response (DDR) pathways are responsible for repairing endogenous or exogenous DNA damage to maintain the stability of the cellular genome, including homologous recombination repair (HRR) pathway, mismatch repair (MMR) pathway, etc. In ovarian cancer, current studies are focused on HRR genes, especially BRCA1/2, and the results show regional and population differences. To characterize germline mutations in DDR genes in ovarian cancer in Southwest China, 432 unselected ovarian cancer patients underwent multi-gene panel testing from October 2016 to October 2020. Overall, deleterious germline mutations in DDR genes were detected in 346 patients (80.1%), and in BRCA1/2 were detected in 126 patients (29.2%). The prevalence of deleterious germline mutations in BRCA2 is higher than in other studies (patients are mainly from Eastern China), and so is the mismatch repair genes. We identified three novel BRCA1/2 mutations, two of which probably deleterious (BRCA1 p.K1622* and BRCA2 p.L2987P). Furthermore, we pointed out that deleterious mutations of FNACD2 and RECQL4 are potential ovarian cancer susceptibility genes and may predispose carriers to ovarian cancer. In conclusion, our study highlights the necessity of comprehensive germline mutation detection of DNA damage response genes in ovarian cancer patients, which is conducive to patient management and genetic counseling., (© 2024. The Author(s).)

Scanning electron microscopy (SEM) is a crucial tool for analyzing submicron-scale structures. However, the attainment of high-quality SEM images is contingent upon the high conductivity of the material due to constraints imposed by its imaging principles. For weakly conductive materials or structures induced by intrinsic properties or organic doping, the SEM imaging quality is significantly compromised, thereby impeding the accuracy of subsequent structure-related analyses. Moreover, the unavailability of paired high-low quality images in this context renders the supervised-based image processing methods ineffective in addressing this challenge. Here, an unsupervised method based on Cycle-consistent Generative Adversarial Network (CycleGAN) was proposed to enhance the quality of SEM images for weakly conductive samples. The unsupervised model can perform end-to-end learning using unpaired blurred and clear SEM images from weakly and well-conductive samples, respectively. To address the requirements of material structure analysis, an edge loss function was further introduced to recover finer details in the network-generated images. Various quantitative evaluations substantiate the efficacy of the proposed method in SEM image quality improvement with better performance than the traditional methods. Our framework broadens the application of artificial intelligence in materials analysis, holding significant implications in fields such as materials science and image restoration., (© 2024. The Author(s).)

This study is nationwide multicenter epidemiological research, aimed at investigating the distribution changes and seasonal patterns of various airborne allergens among preschool children with allergic rhinitis (AR) in different regions of China, and analyzing the clinical correlation between sensitization to various airborne allergens and AR symptoms in children. Information on children was collected through standard questionnaires, and total IgE (tIgE) and specific IgE (sIgE) for 11 inhalant allergens were tested. The results showed that dust mites are the primary allergens for preschool AR children (39%). Among pollen allergens, Amb a had the highest positivity rate (8.1%), followed by Art v (7.8%). The sensitization rates for two mites peaked in May (46.9% and 40.6%). Art v peaked in August (21.5%), while Amb a had peaks in May (12.7%) and August (17.8%). The sensitization peaks for various tree pollens mainly occurred in August. In the Eastern monsoon region, the sensitization rate to mites was significantly higher than in the Northwest arid and semi-arid regions; whereas, for pollen allergens, the sensitization rates to Amb a, Pla a, Pin a, Pop d, and Bet v were significantly higher in the Northwest arid and semi-arid regions than in the Eastern monsoon region. The correlation among various tree pollens, specifically between Pla a, Pin r, Pop d, and Bet v was strong (0.63 ~ 0.79), with a cross-overlapping percentage of 53.9%. Children with multiple pollen sensitizations had higher cumulative nasal symptom scores than those negative for pollen (P < 0.01). Children with only pollen sensitization had higher cumulative rhinitis symptom scores than the all-negative group (P < 0.0001) and the mite-only sensitization group [P < 0.05], while the mite-only sensitization group also had higher scores than the all-negative group [P < 0.05], and the group sensitized to both pollen and mites had lower scores than the pollen-only group [P < 0.05]. This study indicates that sensitization to mites and grass pollens exhibits significant regional differences, with grass pollen allergies primarily occurring in autumn, sensitization to pollens in general exhibits a pronounced seasonal pattern. Moreover, pollen sensitization aggravates nasal and ocular symptoms in AR children., (© 2024. The Author(s).)

The association between the anatomical features of teeth and the pathogenesis of periodontitis is well-documented. This study aimed to evaluate the influence of the mesial concavity of the maxillary first premolar on periodontal clinical indices and alveolar bone resorption rates. Employing a cross-sectional design, in 226 patients with periodontitis, we used cone beam computed tomography(CBCT) to examine the mesial concavity and alveolar bone resorption of 343 maxillary first premolar. Periodontal clinical indicators recorded by periodontal probing in the mesial of the maxillary first premolar in patients with periodontitis. Our findings indicate that the presence of mesial concavity at the cemento-enamel junction of the maxillary first premolar was not significantly influenced by either tooth position or patient sex (p > 0.05). Nonetheless, the mesial concavity at the cemento-enamel junction of the maxillary first premolar was found to exacerbate alveolar bone resorption and the inflammatory condition (p < 0.05). We infer that the mesial concavity at the cemento-enamel junction of the maxillary first premolar may contribute to localized alveolar bone loss and accelerate the progression of periodontal disease., (© 2024. The Author(s).)

Anoikis resistance, a notable factor in osteosarcoma, plays a significant role in tumor invasion and metastasis. This study seeks to identify a distinct gene signature that is specifically associated with the anoikis subcluster in osteosarcoma. Clinical, single-cell, and transcriptional data from TARGET and GEO datasets were used to develop a gene signature for osteosarcoma based on the anoikis subcluster. Univariate Cox and LASSO regression analyses were employed. The signature's predictive value was evaluated using time-dependent ROC and Kaplan-Meier analyses. Functional enrichment analyses and drug sensitivity analyses were conducted. Validation of three modular genes was performed using RT-qPCR and Western blotting. Signature (ZNF583, CGNL1, CXCL13) was developed to predict overall survival in osteosarcoma patients, targeting the anoikis subcluster. The signature demonstrated good performance in external validation. Stratification based on the signature revealed significantly different prognoses. The signature was an independent prognostic factor. The low-risk group showed enhanced immune cell infiltration and improved immune function. Drug sensitivity analysis indicated efficacy of chemotherapy agents. Prognostic nomograms incorporating the signature provided greater predictive accuracy and clinical utility. Signatures related to the anoikis subcluster play a significant role in osteosarcoma progression. Incorporating these findings into clinical decision-making can improve osteosarcoma treatment and patient outcomes., (© 2023. The Author(s).)

Intelligent Transportation has seen significant advancements with Deep Learning and the Internet of Things, making Traffic Signal Control (TSC) research crucial for reducing congestion, travel time, emissions, and energy consumption. Reinforcement Learning (RL) has emerged as the primary method for TSC, but centralized learning poses communication and computing challenges, while distributed learning struggles to adapt across intersections. This paper presents a novel approach using Federated Learning (FL)-based RL for TSC. FL integrates knowledge from local agents into a global model, overcoming intersection variations with a unified agent state structure. To endow the model with the capacity to globally represent the TSC task while preserving the distinctive feature information inherent to each intersection, a segment of the RL neural network is aggregated to the cloud, and the remaining layers undergo fine-tuning upon convergence of the model training process. Extensive experiments demonstrate reduced queuing and waiting times globally, and the successful scalability of the proposed model is validated on a real-world traffic network in Monaco, showing its potential for new intersections., (© 2023. The Author(s).)

Internet search data was a useful tool in the pre-warning of COVID-19. However, the lead time and indicators may change over time and space with the new variants appear and massive nucleic acid testing. Since Omicron appeared in late 2021, we collected the daily number of cases and Baidu Search Index (BSI) of seven search terms from 1 January to 30 April, 2022 in 12 provinces/prefectures to explore the variation in China. Two search peaks of "COVID-19 epidemic", "Novel Coronavirus" and "COVID-19" can be observed. One in January, which showed 3 days lead time in Henan and Tianjin. Another on early March, which occurred 0-28 days ahead of the local epidemic but the lead time had spatial variation. It was 4 weeks in Shanghai, 2 weeks in Henan and 5-8 days in Jilin Province, Jilin and Changchun Prefecture. But it was only 1-3 days in Tianjin, Quanzhou Prefecture, Fujian Province and 0 day in Shenzhen, Shandong Province, Qingdao and Yanbian Prefecture. The BSI was high correlated (r s :0.70-0.93) to the number of cases with consistent epidemiological change trend. The lead time of BSI had spatial and temporal variation and was close related to the strength of nucleic acid testing. The case detection ability should be strengthened when perceiving BSI increase., (© 2023. Springer Nature Limited.)

A drug-loaded diaphragm is an easy-to-use and effective drug delivery system that is often used to treat mouth ulcers. In this study, an ultrafine fiber film loaded with capsaicin was successfully prepared using the electrospinning technology. poly-L-lactic acid and gelatin were selected as the matrix materials to form the composite fiber, and trifluoroethanol was used as a co-solvent for poly-L-lactic acid, gelatin and capsaicin to prepare the spinning solution, which was simple to fabricate. The prepared fiber films were characterized based on their microscopic morphology and tested to derive their mechanical properties. Thereafter, the capsaicin release behavior of the film was investigated. In vitro experiments revealed certain anti-inflammatory and antibacterial abilities while animal experiments revealed that the capsaicin-loaded ultrafine fiber film could promote the healing of oral ulcers in rats. Healing of the tongue tissue in rats administered 10% capsaicin-loaded fiber film was found to be better than that in rats administered the commercial dexamethasone patch. Overall, this development strategy may prove to be promising for the development of oral ulcer patch formulations., (© 2023. Springer Nature Limited.)

The tumour microenvironment (TME) is vital to tumour development and influences the immunotherapy response. Abnormal nucleotide metabolism (NM) not only promotes tumour cell proliferation but also inhibits immune responses in the TME. Therefore, this study aimed to determine whether the combined signatures of NM and the TME could better predict the prognosis and treatment response in gastric cancer (GC). 97 NM-related genes and 22 TME cells were evaluated in TCGA-STAD samples, and predictive NM and TME characteristics were determined. Subsequent correlation analysis and single-cell data analysis illustrated a link between NM scores and TME cells. Thereafter, NM and TME characteristics were combined to construct an NM-TME classifier. Patients in the NMlow/TMEhigh group exhibited better clinical outcomes and treatment responses, which could be attributed to the differences in immune cell infiltration, immune checkpoint genes, tumour somatic mutations, immunophenoscore, immunotherapy response rate and proteomap. Additionally, the NMhigh/TMElow group benefited more from Imatinib, Midostaurin and Linsitinib, while patients in the NMlow/TMEhigh group benefited more from Paclitaxel, Methotrexate and Camptothecin. Finally, a highly reliable nomogram was developed. In conclusion, the NM-TME classifier demonstrated a pretreatment predictive value for prognosis and therapeutic responses, which may offer novel strategies for strategizing patients with optimal therapies., (© 2023. The Author(s).)

Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous malignancy with poor prognosis. This article aims to explore the clinical significance of cell differentiation trajectory in HNSCC, identify different molecular subtypes by consensus clustering analysis, and develop a prognostic risk model on the basis of differentiation-related genes (DRGs) for predicting the prognosis of HNSCC patients. Firstly, cell trajectory analysis was performed on single-cell RNA sequencing (scRNA-seq) data, four molecular subtypes were identified from bulk RNA-seq data, and the molecular subtypes were predictive of patient survival, clinical features, immune infiltration status, and expression of immune checkpoint genes (ICGs)s. Secondly, we developed a 10-DRG signature for predicting the prognosis of HNSCC patients by using weighted correlation network analysis (WGCNA), differential expression analysis, univariate Cox regression analysis, and multivariate Cox regression analysis. Then, a nomogram integrating the risk assessment model and clinical features can successfully predict prognosis with favorable predictive performance and superior accuracy. We projected the response to immunotherapy and the sensitivity of commonly used antitumor drugs between the different groups. Finally, we used the quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) analysis and western blot to verify the signature. In conclusion, we identified distinct molecular subtypes by cell differentiation trajectory and constructed a novel signature based on differentially expressed prognostic DRGs, which could predict the prognosis and response to immunotherapy for patients and may provide valuable clinical applications in the treatment of HNSCC., (© 2022. The Author(s).)

Palmitoleic acid, a monounsaturated fatty acid which could affect glucose and lipid metabolism and reduce insulin resistance has two isomers, i.e. cis-palmitoleic acid (cPOA) and trans-palmitoleic acid (tPOA). However, the pharmacokinetic, metabolic transformation and structure-activity relationship of the two isomers have not been reported. A precise and accurate ultra performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) method was developed to determine cPOA and tPOA simultaneously. Both the cPOA and tPOA were administered i.g. (intragastric gavage) to rats at 75 mg/kg. Serum samples were collected and analyzed for the two isomers by UPLC-MS/MS on a reverse-phase BDS C18 column equilibrated and eluted with water (A) and acetonitrile (B) at a flow rate of 0.3 mL/min. The calibration curves for cPOA and tPOA were linear over the range 0.1-12 μg/mL. Analytes were monitored by selected-reaction monitoring in negative electrospray ionization mode. The Tmax of cPOA was 0.94 ± 0.44 h and the Cmax 8.17 ± 1.97 μg/L, and the Tmax and Cmax of tPOA were 1.50 ± 0.98 h and 14.77 ± 11.91 μg/L, respectively. AUC 0-24 h of cPOA and tPOA were 59.45 ± 29.83 and 113.88 ± 72.25 mg/L·h. The method was applied in pharmacokinetic study of cPOA and tPOA in rat serum successfully. Besides, the concentrations of cPOA and tPOA in rat serums were observed fluctuating with a consistent trend, which may be due to reciprocal bio-convert in the body., (© 2022. The Author(s).)

We compared the clinical utility of single-shot echo-planar imaging (SS-EPI) using different breathing schemes, readout-segmented EPI and zoomit EPI in the repeatability of apparent diffusion coefficient (ADC) measurements, cortico-medullary contrast to noise ratio (c-mCNR) and image quality. In this institutional review board-approved prospective study, some common clinically applicable diffusion-weighted imaging (b = 50, 400, 800 s/mm 2 ) of kidney on 3.0 T MRI were performed on 22 volunteers using SS-EPI with breath-hold diffusion-weighted imaging (BH-DWI), free-breathing (FB-DWI), navigator-triggered (NT-DWI) and respiratory-triggered (RT-DWI), readout-segmented DWI (RS-DWI), and Zoomit DWI (Z-DWI). ADC and c-mCNR were measured in 12 anatomic locations (the upper, middle, and lower pole of the renal cortex and medulla), and image quality was assessed on these DWI sequences. A DWI with the optimal clinical utility was decided by systematically assessing the ADC repeatability, c-mCNR and image quality among the DWIs. For ADC measurements, Z-DWI had an excellent intra-observer agreement (intra-class correlation coefficients (ICCs): 0.876-0.944) and good inter-observer agreement (inter-class ICCs: 0.798-0.856) in six DWI sequences. Z-DWI had the highest ADC repeatability in most of the 12 anatomic locations of the kidneys (mean ADC absolute difference: 0.070-0.111 × 10 -3  mm 2 /s, limit of agreement: 0.031-0.056 × 10 -3  mm 2 /s). In all DWIs, Z-DWI yielded a slightly higher c-mCNR than other DWIs in most representative locations (P > 0.05), which was significantly higher than BH-DWI and FB-DWI in the middle pole of both kidneys and the upper pole of the left kidney (P < 0.05). In addition, Z-DWI yielded image quality that was similar to RT-DWI and NT-DWI (P > 0.05) and superior to BH-DWI, FB-DWI and RS-DWI (P < 0.05). Our results suggest that Z-DWI provides the highest ADC reproducibility, better c-mCNR and good image quality on 3.0 T MRI, making it the recommended sequence for clinical DWI of the kidney., (© 2022. The Author(s).)

Strategies for treating osteoarthritis (OA) have become a research focus because an effective treatment for OA is unavailable. The objective of this study was to explore the effects and underlying mechanisms of glutamine (Gln) in OA. First, the chondrocytes were identified and a standard IL-1β-induced OA model was established. After treatment with Gln or saline, the viability and apoptosis of chondrocytes were evaluated using a CCK-8 assay and flow cytometry analysis, which revealed that Gln can improve the IL-1β-induced OA cells. Meanwhile, Gln can enhance the expression of aggrecan and collagen II, which are protective proteins for articular cartilage. Instead, Gln inhibited the expression of matrix metalloproteinase-1 (MMP-1) and matrix metalloproteinase-13 (MMP-13), which can degrade cartilage. To better understand the underlying mechanisms of Gln in IL-1β-induced chondrocytes, the classical OA pathways of JNK and NF-κB were examined at the protein and mRNA levels using western blot and qRT-PCR analyses. We found that JNK and NF-κB were downregulated gradually depending on the Gln dose and protective and destructive factors changed based on changes of JNK and NF-κB. The effects of high-dose Gln were more effective than low-dose. Moreover, Gln was applied to the animal OA model to check the effects in vivo. The results showed that Gln attenuated cartilage degeneration and decreased OARSI scores, which demonstrated that Gln can improve OA. The experiments showed that Gln can benefit mice with OA by inhibiting the JNK and NF-κB signaling pathways., (© 2022. The Author(s).)

Surface defect detection is a vital process in industrial production and a significant research direction in computer vision. Although today's deep learning defect detection methods based on computer vision can achieve high detection accuracy, they are mainly based on supervised learning. They require many defect samples to train the model, which is not compatible with the current situation that industrial defect sample is difficult to obtain and costly to label. So we propose a new unsupervised small sample defect detection model-ISU-GAN, which is based on the CycleGAN architecture. A skip connection, SE module, and Involution module are added to the Generator, enabling the feature extraction capability of the model to be significantly improved. Moreover, we propose an SSIM-based defect segmentation method that applies to GAN-based defect detection and can accurately extract defect contours without the need for redundant noise reduction post-processing. Experiments on the DAGM2007 dataset show that the unsupervised ISU-GAN can achieve higher detection accuracy and finer defect profiles with less than 1/3 of the unlabelled training data than the supervised model with the full training set. Relative to the supervised segmentation models UNet and ResUNet++ with more training samples, our model improves the detection accuracy by 2.84% and 0.41% respectively and the F1 score by 0.025 and 0.0012 respectively. In addition, the predicted profile obtained using our method is closer to the real profile than other models used for comparison., (© 2022. The Author(s).)

This meta-analysis was aimed to estimate the diagnostic performance of volatile organic compounds (VOCs) as a potential novel tool to screen for the neoplasm of the digestive system. An integrated literature search was performed by two independent investigators to identify all relevant studies investigating VOCs in diagnosing neoplasm of the digestive system from inception to 7th December 2020. STATA and Revman software were used for data analysis. The methodological quality of each study was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. A bivariate mixed model was used and meta-regression and subgroup analysis were performed to identify possible sources of heterogeneity. A total of 36 studies comprised of 1712 cases of neoplasm and 3215 controls were included in our meta-analysis. Bivariate analysis showed a pooled sensitivity of 0.87 (95% confidence interval (CI) 0.83-0.90), specificity of 0.86 (95% CI 0.82-0.89), a positive likelihood ratio of 6.18 (95% CI 4.68-8.17), and a negative likelihood ratio of 0.15 (95% CI 0.12-0.20). The diagnostic odds ratio and the area under the summary ROC curve for diagnosing neoplasm of the digestive system were 40.61 (95% CI 24.77-66.57) and 0.93 (95% CI 0.90-0.95), respectively. Our analyses revealed that VOCs analysis could be considered as a potential novel tool to screen for malignant diseases of the digestive system., (© 2021. The Author(s).)

Panonychus citri, a major citrus pest. In pest management, bifenazate is a novel acaricide with high biological activity against red mites, such as Tetranychus urticae Koch. However, in the field, pests are frequently exposed to sublethal or lethal concentrations of pesticides. At present, its sublethal effects on P. citri have not been reported. Therefore, in order to investigate sublethal effect of bifenazate on biological traits and enzymatic properties of P. citri. The newly emerged females were treated with two concentrations of bifenazate: LC 10 and LC 30 , the development and fecundity were observed. The results showed that female adult duration, fecundity, oviposition days, longevity were decrease compared with control, but pre-oviposition period was longer, net reproductive rate (R 0 ), mean generation (T) were decreased, intrinsic rate of increase (rm), finite rate (λ) were decreased in LC 30 , however, doubling time was increased. Enzymatic tests showed that CAT, POD, CarE activities were higher in treatments than control. The SOD and GST activities were lower in LC 30 than control and LC 10 , the CYP450 activity was decreased with the increasing concentrations. This study demonstrated that low lethal concentrations of bifenazate adversely affected life table parameters, enzymatic properties in P. citri. Therefore, bifenazate has the potential to control this pest., (© 2021. The Author(s).)

The long-noncoding RNA colorectal neoplasia differentially expressed (CRNDE) gene has been considered to be crucial in tumor malignancy. Although CRNDE is highly expressed in acute myeloid leukemia (AML), its mechanism of action remains unknown. In this study, GEPIA and qRT-PCR were performed to confirm the expression of CRNDE in AML samples and cell lines, respectively. CRNDE shRNA vectors were transfected to explore the biological functions of CRNDE. The cell proliferation was assessed by the CCK8 assay, while apoptosis and cell cycle distribution were measured by flow cytometry and Western blotting. The results showed that CRNDE was overexpressed in both AML samples and cell lines. CRNDE silencing inhibited proliferation and increased apoptotic rate and cell cycle arrest of KG-1a cells. The luciferase reporter assay coupled with RIP assay revealed that CRNDE act as a ceRNA. Rescue assays demonstrated that the effects of CRNDE silencing could be reversed by miR-136-5p inhibitors. In conclusion, our results expound that the CRNDE/miR-136-5p/MCM5 axis modulates cell progression and provide a new regulatory network of CRNDE in KG-1a cells., (© 2021. The Author(s).)

Microbial contamination in drinking water has become an important threat to human health. There is thus an urgent need to develop antibacterial materials to treat drinking water. Here, porous silver-loaded biochar (C-Ag) was prepared using corn straw as the substrate and silver as the antibacterial agent. C-Ag was then uniformly distributed in polyvinyl alcohol gel beads of eluted calcium carbonate to prepare p-PVA/C-Ag antibacterial composite. The polymer composites were tested by FT-IR, XRD, SEM and TG-DSC. The results showed that C-Ag was more evenly distributed in the PVA gel spheres. Antibacterial experiments showed that p-PVA/C-Ag greatly inhibited Escherichia coli. Practical application tests revealed that p-PVA/C-Ag showed high and sustained bactericidal inhibition and reusability. Generally, p-PVA/C-Ag composite shows high potential to be applied to drinking water treatment.

To determine the factors predicting the probability of severe postpartum hemorrhage (SPPH) in women undergoing repeat cesarean delivery (RCD). This multicenter, retrospective cohort study involved women who underwent RCD from January 2017 to December 2017, in 11 public tertiary hospitals within 7 provinces of China. The all-variables model and the multivariable logistic regression model (pre-operative, operative and simple model) were developed to estimate the probability of SPPH in development data and external validated in validation data. Discrimination and calibration were evaluated and clinical impact was determined by decision curve analysis. The study consisted of 11,074 women undergoing RCD. 278 (2.5%) women experienced SPPH. The pre-operative simple model including 9 pre-operative features, the operative simple model including 4 pre-operative and 2 intraoperative features and simple model including only 4 closely related pre-operative features showed AUC 0.888, 0.864 and 0.858 in development data and 0.921, 0.928 and 0.925 in validation data, respectively. Nomograms were developed based on predictive models for SPPH. Predictive tools based on clinical characteristics can be used to estimate the probability of SPPH in patients undergoing RCD and help to allow better preparation and management of these patients by using a multidisciplinary approach of cesarean delivery for obstetrician.

Stimulus-dependence of gamma oscillations (GAMMA, 30-90 Hz) has not been fully understood, but it is important for revealing neural mechanisms and functions of GAMMA. Here, we recorded spiking activity (MUA) and the local field potential (LFP), driven by a variety of plaids (generated by two superimposed gratings orthogonal to each other and with different contrast combinations), in the primary visual cortex of anesthetized cats. We found two distinct narrow-band GAMMAs in the LFPs and a variety of response patterns to plaids. Similar to MUA, most response patterns showed that the second grating suppressed GAMMAs driven by the first one. However, there is only a weak site-by-site correlation between cross-orientation interactions in GAMMAs and those in MUAs. We developed a normalization model that could unify the response patterns of both GAMMAs and MUAs. Interestingly, compared with MUAs, the GAMMAs demonstrated a wider range of model parameters and more diverse response patterns to plaids. Further analysis revealed that normalization parameters for high GAMMA, but not those for low GAMMA, were significantly correlated with the discrepancy of spatial frequency between stimulus and sites' preferences. Consistent with these findings, normalization parameters and diversity of high GAMMA exhibited a clear transition trend and region difference between area 17 to 18. Our results show that GAMMAs are also regulated in the form of normalization, but that the neural mechanisms for these normalizations might differ from those of spiking activity. Normalizations in different brain signals could be due to interactions of excitation and inhibitions at multiple stages in the visual system.

Prognosis of patients with lung cancer remains extremely poor; thus, we sought to unearth novel competing endogenous RNA (ceRNA) networks associated with the prognosis of lung adenocarcinoma (LUAD). Aberrant mRNAs were identified from the intersection of three Gene Expression Omnibus (GEO) datasets. A protein-protein interaction (PPI) network was constructed, and miRNAs and long noncoding RNAs (lncRNAs) upstream of mRNAs were predicted. In the present study, 402 upregulated and 638 downregulated genes in lung cancer tissues were identified. Functional analysis showed significant enrichment of cancer pathways. In these top hub genes, 10 upregulated and 7 downregulated genes had substantial prognostic values in LUAD. Thirty-seven miRNAs were predicted to target 17 key genes, and only five miRNAs exhibited prognostic correlation. Through stepwise reverse prediction and validation from miRNA to lncRNA, four key lncRNAs were identified using expression and survival analysis. Ultimately, the co-expression analysis identified LINC00665-miR-let-7b-CCNA2 as the key ceRNA network associated with the prognosis of LUAD. We successfully constructed a novel ceRNA network wherein each component was significantly associated with the prognosis of LUAD. Hence, we propose that this network may provide key biomarkers or potential therapeutic targets for LUAD prognosis.

Environmental natural organic matters (NOMs) have great effects on the physicochemical properties of engineering nanoparticles, which may impact the transport of nanoparticles across plasma membrane and the cytotoxicity. Therefore, the kinetics, uptake pathway and mass of transporting into A549 cell membrane of silver nanoparticles (AgNPs) coated with citric acid (CA), tartaric acid (TA) and fulvic acid (FA) were investigated, respectively. CA, FA and TA enhanced the colloidal stability of AgNPs in culture medium and have greatly changed the surface plasmon resonance spectrum of AgNPs due to the absorption of CA, FA and TA on surface of AgNPs. Internalizing model showed that velocity of CA-, TA- and FA-nAg transporting into A549 cell were 5.82-, 1.69- and 0.29-fold higher than those of the control group, respectively. Intracellular mass of Ag was dependent on mass of AgNPs delivered to cell from suspension, which obeyed Logistic model and was affected by NOMs that CA- and TA-nAg showed a large promotion on intracellular mass of Ag. The lipid raft/caveolae-mediated endocytosis (LME) of A549 cell uptake of AgNPs were susceptible to CA, TA and FA that uptake of CA-, TA- and FA-nAg showed lower degree of dependent on LME than that of the control (uncoated AgNPs). Actin-involved uptake pathway and macropinocytosis would have less contribution to uptake of FA-nAg. Overall, transmembrane transport of NOMs-coated AgNPs differs greatly from that of the pristine AgNPs.

Curvature-based three-dimensional cardiovascular magnetic resonance (CMR) allows regional function characterization without an external spatial frame of reference. However, introduction of this modality into clinical practice is hampered by lack of reference values. We aim to establish normal ranges for 3D left ventricular (LV) regional parameters in relation to age and gender for 171 healthy subjects. LV geometrical reconstruction and automatic calculation of regional parameters were implemented by in-house software (CardioWerkz) using stacks of short-axis cine slices. Parameter normal ranges were stratified by gender and age categories (≤44, 45-64, 65-74 and 75-84 years). Our software had excellent intra- and inter-observer agreement. Ageing was significantly associated with increases in end-systolic (ES) curvedness (C ES ) and area strain (AS) with higher rates of increase in males, end-diastolic (ED) and ES wall thickness (WT ED , WT ES ) with higher rates of increase in females, and reductions in ED and ES wall stress indices (σ i,ED ) with higher rates of increase in females. Females exhibited greater ED curvedness, C ES , σ i,ED and AS than males, but smaller WT ED and WT ES . Age × gender interaction was not observed for any parameter. This study establishes age and gender specific reference values for 3D LV regional parameters using CMR without additional image acquisition.

The global left ventricular (LV) contractility index, dσ*/dt max measures the maximal rate of change in pressure-normalized LV wall stress. We aim to describe the trend of dσ*/dt max in differing severity of aortic stenosis (AS) with preserved left ventricular ejection fraction (LVEF) and the association of dσ*/dt max with clinical outcomes in moderate AS and severe AS. We retrospectively studied a total of 1738 patients with AS (550 mild AS, 738 moderate AS, 450 severe AS) and preserved LVEF ≥ 50% diagnosed from 1 st January 2001 to 31 st December 2015. dσ*/dt max worsened with increasing severity of AS despite preserved LVEF (mild AS: 3.69 ± 1.28 s -1 , moderate AS: 3.17 ± 1.09 s -1 , severe AS: 2.58 ± 0.83 s -1 , p < 0.001). Low dσ*/dt max  < 2.8 s -1 was independently associated with a higher composite outcome of aortic valve replacement, congestive cardiac failure admissions and all-cause mortality (adjusted hazard ratio 1.48, 95% CI: 1.25-1.77, p < 0.001). In conclusion, dσ*/dt max declined with worsening AS despite preserved LVEF. Low dσ*/dt max  < 2.8 s -1 was independently associated with adverse clinical outcomes in moderate AS and severe AS with preserved LVEF.

Allergic responses are mainly caused by IgE, which is often located on the cell surface. The current diagnostic method detects both allergen-specific IgE and total IgE levels, but a number of allergic patients have a normal serum IgE level, which is a poor clinical correlate for allergy. Here, we developed a simple method to detect the level of cell-bound IgE by dissociating it from blood cells with lactic acid. Dissociated cell-bound IgE and plasma IgE levels were detected using the same ELISA kit at the same time. We established two clinical cohorts: an allergic patient group and a healthy participant group. In general, cell-bound IgE correlated well with plasma IgE; however, some patients exhibited high cell-bound IgE levels but low plasma IgE levels. We recommended 350 ng/mL peripheral blood total IgE (cell-bound IgE + plasma IgE) as the cut-off value for allergy diagnosis. Using this indicator, 90.32% of our allergic patients were correctly diagnosed. The peripheral blood total IgE level is a promising clinical diagnostic indicator in allergic patients and will provide more guidance for allergy diagnosis and therapeutic evaluation.

Tibetan pig is native to the Qinghai-Tibet Plateau and has adapted to the high-altitude environmental condition such as hypoxia. However, its origin and genetic mechanisms underlying high-altitude adaptation still remain controversial and enigmatic. Herein, we analyze 229 genomes of wild and domestic pigs from Eurasia, including 63 Tibetan pigs, and detect 49.6 million high-quality variants. Phylogenomic and structure analyses show that Tibetan pigs have a close relationship with low-land domestic pigs in China, implying a common domestication origin. Positively selected genes in Tibetan pigs involved in high-altitude physiology, such as hypoxia, cardiovascular systems, UV damage, DNA repair. Three of loci with strong signals of selection are associated with EPAS1, CYP4F2, and THSD7A genes, related to hypoxia and circulation. We validated four non-coding mutations nearby EPAS1 and CYP4F2 showing reduced transcriptional activity in Tibetan pigs. A high-frequency missense mutation is found in THSD7A (Lys561Arg) in Tibetan pigs. The selective sweeps in Tibetan pigs was found in association with selection against non-coding variants, indicating an important role of regulatory mutations in Tibetan pig evolution. This study is important in understanding the evolution of Tibetan pigs and advancing our knowledge on animal adaptation to high-altitude environments.

Dendranthema indicum var. aromaticum plant has been widely used as herbal medicine in China, however, the material basis responsible for the therapeutic benefits remains largely unclear. This study aimed to provide an optimized method for extracting and characterizing phenolic compounds in D. indicum var. aromaticum flower. Firstly, an ultrasound-assisted method combined with central composite circumscribed (CCC) design was applied to optimize phenolic compound extraction. Ethanol-acetic acid (70%:2%, v/v) was selected as solvent, and the optimal extraction condition was: extraction temperature, 57 °C; solid/liquid ratio, 1:30 g/mL; extraction time, 20 min. Secondly, an effective and economic HPLC-PDA-ESI-MS n method was established and validated for phenolic compound characterization and quantification. As a result, 14 phenolic compounds were identified, including 8 phenolic acids and 6 flavonoids, and for the first time, oleuropein derivatives, chrysoeriol, and tricin are reported in D. indicum var. aromaticum flower. The content of phenolics identified by HPLC-MS n was 6.42 ± 0.32 mg/g DW. The optimized method for extraction and characterization of phenolic compounds has significant meaning to future pharmaceutical and medicinal research on D. indicum var. aromaticum, and the results in this study can provide references for herbal research.

Falls in late postmenopausal women with osteopenia usually cause fractures with severe consequences. This 36-month randomized, double-blind and placebo-controlled trial with a 10-year observational follow-up study aimed to investigate the long-term effect of herbal formula Bushen Yijing Fang (BSYJF) on fall risk in the late postmenopausal women with osteopenia. 140 late postmenopausal women (Femoral neck T-score, -2.5~-2 SD) were recruited and randomized to orally receive calcium carbonate 300 mg daily with either BSYJF or placebo for 36 months. The effect was further investigated for another 10-year follow-up. During the 36-month administration, there were 12 falls in BSYJF group and 28 falls in placebo group, respectively, indicating 64% lower risk of falls (RR 0.36 [95% CI, 0.18 to 0.71]; P = 0.004) in BSYJF group. During the 10-year follow-up, 36% lower fall risk (RR 0.64 [95% CI, 0.46 to 0.89]; P = 0.009) was observed in BSYJF group. No significant difference was found in safety profile between two groups. Thirty-six-month administration of BSYJF reduced fall risk with an increase in bone mass, and its latent effect on fall risk was continually observed in the 10-year follow-up in late postmenopausal women with osteopenia. This clinical trial was registered at Chinese clinical trial registry (ChiCTR-IOR-16008942).

We propose and demonstrate a novel method to measure dynamic refractive index distributions using a combination of total internal reflection (TIR) and dual-channel simultaneous phase-shifting interferometry (DCSPSI). First, a right-angle prism is introduced into the DCSPSI system, the reflection phase variation induced by TIR, which contains the refractive index information of tested sample, can be achieved by the spatial carrier-frequency phase-shifting algorithm from a pair of interferograms with the phase shifts of π/2 captured by DCSPSI system. Second, based on the relationship between the reflection phase variation and the refractive index, the 2D refractive index distribution can be calculated easily. Importantly, the proposed TIR-DCSPSI method will supply a useful tool for dynamic refractive index distribution measurement of dynamic process, such as the droplet evaporation, mutual solubilization and diffusion of different droplets, cell culture, colloid curing, etc.

Signaling by members of the transforming growth factor-β (TGF-β) superfamily, such as TGF-β3 and BMP7, and oxygen tension play a pivotal role in chondrocyte biology. The objective of this research was to investigate the endogenous BMP7 expression in human osteoarthritis (OA) cartilage and the effect of oxygen tension on the single or combined treatment with TGF-β3 and BMP7 on OA chondrocyte redifferentiation in three dimensional (3D) pellet cultures. The results showed the expression of BMP7 and its intracellular signaling target SMAD1/5/8 was decreased in early OA, while it was increased in later stages of OA. The combined treatment with TGF-β3 and BMP7, both in normoxia and hypoxia, was more effective than TGF-β3 or BMP7 alone in redifferentiating chondrocytes. This was reflected by Alcian blue/Safranin O staining and collagen type II protein expression, as well as by gene expression. Hypoxia elevated TGF-β3 and BMP7-induced matrix formation of OA chondrocytes and alleviated the catabolic gene expression. Interestingly, cells cultured under normoxia displayed mild signs of an inflammatory stress response, which was effectively counteracted by culturing the cells under low oxygen tension. Our data underscores the important modulatory role of oxygen tension on the chondrocyte's responsiveness to TGF-β3 and/or BMP7.

Among community cohorts, associations between clinical and metabolite factors and complex left atrial (LA) phasic function assessed by cardiac magnetic resonance (CMR) feature tracking (FT) are unknown. Longitudinal LA strain comprising reservoir strain (εs), conduit strain (εe) and booster strain (εa) and their corresponding peak strain rates (SRs, SRe, SRa) were measured using CMR FT. Targeted mass spectrometry measured 83 circulating metabolites in serum. Sparse Principal Component Analysis was used for data reduction. Among community adults (n = 128, 41% female) (mean age: 70.5 ± 11.6 years), age was significantly associated with εs (β = -0.30, p < 0.0001), εe (β = -0.3, p < 0.0001), SRs (β = -0.02, p < 0.0001), SRe (β = 0.04, p < 0.0001) and SRe/SRa (β = -0.01, p = 0.012). In contrast, heart rate was significantly associated with εa (β = 0.1, p = 0.001) and SRa (β = -0.02, p < 0.0001). Serine was significantly associated with εs (β = 10.1, p = 0.015), SRs (β = 0.5, p = 0.033) and SRa (β = -0.9, p = 0.016). Citrulline was associated with εs (β = -4.0, p = 0.016), εa (β = -3.4, p = 0.002) and SRa (β = 0.4, p = 0.019). Valine was associated with ratio of SRe:SRa (β = -0.4, p = 0.039). Medium and long chain dicarboxyl carnitines were associated with εs (β = -0.6, p = 0.038). Phases of LA function were differentially associated with clinical and metabolite factors. Metabolite signals may be used to advance mechanistic understanding of LA disease in future studies.