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Abstract Objective Alzheimer's disease (AD) is characterized by the progressive degeneration and damage of neurons in the brain. However, developing an accurate diagnostic assay using blood samples remains a challenge in clinic practice. The aim of this study was to explore senescence‐associated secretory phenotypes (SASPs) in peripheral blood using mass spectrometry based multi‐omics approach and to establish diagnostic assays for AD. Methods This retrospective study included 88 participants, consisting of 29 AD patients and 59 cognitively normal (CN) individuals. Plasma and serum samples were examined using high‐resolution mass spectrometry to identify proteomic and metabolomic profiles. Receiver operating characteristic (ROC) analysis was employed to screen biomarkers with diagnostic potential. K‐nearest neighbors (KNN) algorithm was utilized to construct a multi‐dimensional model for distinguishing AD from CN. Results Proteomics analysis revealed upregulation of five plasma proteins in AD, including RNA helicase aquarius (AQR), zinc finger protein 587B (ZNF587B), C‐reactive protein (CRP), fibronectin (FN1), and serum amyloid A‐1 protein (SAA1), indicating their potential for AD classification. Interestingly, KNN‐based three‐dimensional model, comprising AQR, ZNF587B, and CRP, demonstrated its high accuracy in AD recognition, with evaluation possibilities of 0.941, 1.000, and 1.000 for the training, testing, and validation datasets, respectively. Besides, metabolomics analysis suggested elevated levels of serum phenylacetylglutamine (PAGIn) in AD. Interpretation The multi‐omics outcomes highlighted the significance of the SASPs, specifically AQR, ZNF587B, CRP, and PAGIn, in terms of their potential for diagnosing AD and suggested neuronal aging‐associated pathophysiology.

Abstract Achieving selective hydrodeoxygenation of α, β-unsaturated carbonyl groups to alkenes poses a substantial challenge due to the presence of multiple functional groups. In this study, we develop a ZnNC-X catalyst (X represents the calcination temperature) that incorporates both Lewis acidic-basic sites and Zn-Nx sites to address this challenge. Among the catalyst variants, ZnNC-900 catalyst exhibits impressive selectivity for alkenes in the hydrodeoxygenation of α, β-unsaturated carbonyl compounds, achieving up to 94.8% selectivity. Through comprehensive mechanism investigations and catalyst characterization, we identify the Lewis acidic-basic sites as responsible for the selective hydrogenation of C=O bonds, while the Zn-Nx sites facilitate the subsequent selective hydrodeoxygenation step. Furthermore, ZnNC-900 catalyst displays broad applicability across a diverse range of unsaturated carbonyl compounds. These findings not only offer valuable insights into the design of effective catalysts for controlling alkene selectivity but also extend the scope of sustainable transformations in synthetic chemistry.

Human exposure to heavy metals, which encompasses both essential and toxic varieties, is widespread. The intestine functions as a critical organ for absorption and metabolism of heavy metals. Gut microbiota plays a crucial role in heavy metal absorption, metabolism, and related processes. Toxic heavy metals (THMs), such as arsenic (As), mercury (Hg), lead (Pb), and cadmium (Cd), can cause damage to multiple organs even at low levels of exposure, and it is crucial to emphasize their potential high toxicity. Nevertheless, certain essential trace elements, including iron (Fe), copper (Cu), and manganese (Mn), play vital roles in the biochemical and physiological functions of organisms at low concentrations but can exert toxic effects on the gut microbiota at higher levels. Some potentially essential micronutrients, such as chromium (Cr), silicon (Si), and nickel (Ni), which were considered to be intermediate in terms of their essentiality and toxicity, had different effects on the gut microbiota and their metabolites. Bidirectional relationships between heavy metals and gut microbiota have been found. Heavy metal exposure disrupts gut microbiota and influences its metabolism and physiological functions, potentially contributing to metabolic and other disorders. Furthermore, gut microbiota influences the absorption and metabolism of heavy metals by serving as a physical barrier against heavy metal absorption and modulating the pH, oxidative balance, and concentrations of detoxification enzymes or proteins involved in heavy metal metabolism. The interactions between heavy metals and gut microbiota might be positive or negative according to different valence states, concentrations, and forms of the same heavy metal. This paper reviews the metabolic interactions of 10 common heavy metals with the gut microbiota and their health implications. This collated information could provide novel insights into the disruption of the intestinal microbiota caused by heavy metals as a potential contributing factor to human diseases.

BackgroundOsteosarcoma (OS) is highly malignant and prone to local infiltration and distant metastasis. Due to the poor outcomes of OS patients, the study aimed to identify differentially expressed genes (DEGs) in OS and explore their role in the carcinogenesis and progression of OS.MethodsRNA sequencing was performed to identify DEGs in OS. The functions of the DEGs in OS were investigated using bioinformatics analysis, and DEG expression was verified using RT-qPCR and Western blotting. The role of SLC25A4 was evaluated using gene set enrichment analysis (GSEA) and then investigated using functional assays in OS cells.ResultsIn all, 8353 DEGs were screened. GO and KEGG enrichment analyses indicated these DEGs showed strong enrichment in the calcium signaling pathway and pathways in cancer. Moreover, the Kaplan-Meier survival analysis showed ten hub genes were related to the outcomes of OS patients. Both SLC25A4 transcript and protein expression were significantly reduced in OS, and GSEA suggested that SLC25A4 was associated with cell cycle, apoptosis and inflammation. SLC25A4-overexpressing OS cells exhibited suppressed proliferation, migration, invasion and enhanced apoptosis.ConclusionSLC25A4 was found to be significantly downregulated in OS patients, which was associated with poor prognosis. Modulation of SLC25A4 expression levels may be beneficial in OS treatment.

BackgroundGiven the significant burden of upper digestive diseases, there has been a substantial increase in the utilization of esophagogastroduodenoscopy (EGD) in China from 2012 to 2019. The objective of this study is to investigate the development, practice, and factors influencing the widespread use of EGD during this period.MethodsTwo national censuses were conducted among all hospitals in mainland China that perform gastrointestinal endoscopy. These censuses aimed to extract information on the infrastructure, volume, and quality of EGD. The analysis of potential factors influencing EGD practice was based on real-world data from open access sources.ResultsFrom 2012 to 2019, the number of hospitals performing EGD in mainland China increased from 1,518 to 2,265 (1.49-fold) in tertiary hospitals and from 3,633 to 4,097 (1.12-fold) in secondary hospitals, respectively. The national utilization rate of EGD also increased from 1,643.53 to 2,018.06 per 100,000 inhabitants, indicating a 1.23-fold increase. Regions with more endoscopists per 100,000 inhabitants (OR 9.61, P

T cell receptor (TCR) T cell therapies target tumor antigens in a human leukocyte antigen (HLA)-restricted manner. Biomarker-defined therapies require validation of assays suitable for determination of patient eligibility. For clinical trials evaluating TCR T cell therapies targeting melanoma-associated antigen A4 (MAGE-A4), screening in studies NCT02636855 and NCT04044768 assesses patient eligibility based on: (1) high-resolution HLA typing and (2) tumor MAGE-A4 testing via an immunohistochemical assay in HLA-eligible patients. The HLA/MAGE-A4 assays validation, biomarker data, and their relationship to covariates (demographics, cancer type, histopathology, tissue location) are reported here. HLA-A∗02 eligibility was 44.8% (2,959/6,606) in patients from 43 sites across North America and Europe. While HLA-A∗02:01 was the most frequent HLA-A∗02 allele, others (A∗02:02, A∗02:03, A∗02:06) considerably increased HLA eligibility in Hispanic, Black, and Asian populations. Overall, MAGE-A4 prevalence based on clinical trial enrollment was 26% (447/1,750) across 10 solid tumor types, and was highest in synovial sarcoma (70%) and lowest in gastric cancer (9%). The covariates were generally not associated with MAGE-A4 expression, except for patient age in ovarian cancer and histology in non-small cell lung cancer. This report shows the eligibility rate from biomarker screening for TCR T cell therapies and provides epidemiological data for future clinical development of MAGE-A4-targeted therapies.

Super-resolution (SR) based on deep learning has been playing an important role in improving the spatial resolution of remote sensing images. Although convolutional neural networks (CNNs) dominate the research of remote sensing image SR, most of them struggle to fully utilize the multilevel features in information transmission. Constantly expanding the network architecture sometimes also leads to an increase in feature redundancy and computational complexity. Moreover, CNN-based methods are unable to generate visually appealing images. To address the aforementioned issues, we propose a multilevel feature fusion attention SR method based on GAN called MFFAGAN. Specifically, we propose a novel enhanced mixed-attention block (EMAB), which enables the network to capture key feature information in both the channel and spatial domains. Meanwhile, in order to enhance the model's ability to extract various features at multiple levels more efficiently, we propose a multilevel feature fusion attention module (MFFAM). The output of each residual block is directly fed into the feature aggregation block and eventually combined with the attention branch. Thus, the network is capable of aggregating these information-rich residual features without any loss to produce more representative features. Experimental results show that our proposed MFFAGAN outperforms most state-of-the-art methods in both quantitative and qualitative metrics.

Abstract To evaluate the changes of dry eye parameters after small incision lenticule extraction (SMILE) surgery in patients with different ocular surface disease index (OSDI) scores. Prospective research. Participants were divided into two groups: Group A, OSDI

Abstract Background High-intensity interval training (HIIT) has been shown to enhance cardiovascular health. However, there is a lack of research investigating the specific cardiovascular effects of different HIIT training modes. Therefore, this study aimed to compare the acute effects of cycling-type high intensity interval training (C-HIIT) and resistance-type high intensity interval training (R-HIIT) on arterial stiffness, cardiac autonomic modulation, and cardiac biomarkers in healthy young men. Methods This is a cross-over randomized trial. Eleven healthy active young men took part in both C-HIIT and R-HIIT. Cardio-ankle vascular index (CAVI), heart rate variability (HRV), and systolic blood pressure (SBP) were measured before, immediately and 30 min after the exercise in C-HIIT and R-HIIT. Meanwhile, blood samples for cardiac troponin-T (cTnT) and amino-terminal pro-B-type natriuretic peptide (NT-proBNP) were assessed using ELISA before, 5min and 35min after exercise. Results There was a significant time × group interaction effect (P = 0.019, η p 2 = 0.182) and time main effect for ⊿CAVI (P

Abstract Background This study seeks to assess the utility of T1 and T2 mapping in distinguishing metastatic lymph nodes from reactive lymphadenopathy in patients with head and neck squamous cell carcinoma (HNSCC), using diffusion-weighted imaging (DWI) as a comparison. Methods Between July 2017 and November 2019, 46 HNSCC patients underwent neck MRI inclusive of T1 and T2 mapping and DWI. Quantitative measurements derived from preoperative T1 and T2 mapping and DWI of metastatic and non-metastatic lymph nodes were compared using independent samples t-test or Mann–Whitney U test. Receiver operating characteristic curves and the DeLong test were employed to determine the most effective diagnostic methodology. Results We examined a total of 122 lymph nodes, 45 (36.9%) of which were metastatic proven by pathology. Mean T2 values for metastatic lymph nodes were significantly lower than those for benign lymph nodes (p

Ferroptosis, a defensive strategy commonly employed by the host cells to restrict pathogenic infections, has been implicated in the development and therapeutic responses of various types of cancer. However, the role of ferroptosis in oncogenic Kaposi's sarcoma-associated herpesvirus (KSHV)-induced cancers remains elusive. While a growing number of non-histone proteins have been identified as acetylation targets, the functions of these modifications have yet to be revealed. Here, we show KSHV reprogramming of host acetylation proteomics following cellular transformation of rat primary mesenchymal precursor. Among them, SERPINE1 mRNA binding protein 1 (SERBP1) deacetylation is increased and required for KSHV-induced cellular transformation. Mechanistically, KSHV-encoded viral interleukin-6 (vIL-6) promotes SIRT3 deacetylation of SERBP1, preventing its binding to and protection of lipoyltransferase 2 (Lipt2) mRNA from mRNA degradation resulting in ferroptosis. Consequently, a SIRT3-specific inhibitor, 3-TYP, suppresses KSHV-induced cellular transformation by inducing ferroptosis. Our findings unveil novel roles of vIL-6 and SERBP1 deacetylation in regulating ferroptosis and KSHV-induced cellular transformation, and establish the vIL-6-SIRT3-SERBP1-ferroptosis pathways as a potential new therapeutic target for KSHV-associated cancers.

Abstract Over the two decades, RNA drugs have gradually made their way from bench to bed. Initially, RNA was not an ideal drug since RNA molecules degrade easily and have a relatively short half‐life in the circulation system. Nevertheless, the chemical modification extended the half‐life of RNA in recent years, which makes RNA drugs a new star in drug discovery industry. RNA molecules hold many properties that facilitate their application as therapeutic drugs. RNAs could fold to form complex conformations to bind to proteins, small molecules, or other nucleic acids, and some even form catalytic centers. Protein‐encoding RNAs are the carriers of genetic information from DNA to ribosomes, and various types of non‐coding RNAs cooperate in the transcription and translation of genetic information through various mechanisms. To date, three mainstream RNA therapies have drawn widespread attention: (1) messenger RNA that encodes therapeutic proteins or vaccine antigens; (2) small interfering RNA, microRNA (miRNA), antisense oligonucleotides that inhibit the activity of pathogenic RNAs; and (3) aptamers that regulate protein activity. Here, we summarized the current research and perspectives of RNA therapies, which may provide innovative highlights for cancer therapy.

Recently, exploration breakthroughs have been made in the Lower Cretaceous sandstone reservoirs in the Doseo Basin, but the identification of reservoir fluid property is difficult due to variable reservoir lithology, complex oil-water contact within and faint responses of the oil zone, which causes the lower accuracy of reservoir fluid property identification with conventional mudlogging and wirelogging techniques. Applying the geochemical logging, fluorescent logging, mud logging and cutting logging technology, in combination with formation test data, this paper distinguishes the crude oil types, analyzes the logging response characteristics of oil zone after water washing, and establishes the interpretation charts and parameter standards for reservoir fluid properties. The crude oil can be divided into two types, namely viscous-heavy and thin-light, based on total hydrocarbon content and component concentration tested by mud logging, features of pyrolysis gas chromatogram and fluorescence spectroscopy. The general characteristics of oil layers experienced water washing include the decrease of total hydrocarbon content and component concentration from mud logging, the decrease of S1 and PS values from geochemical logging, the decrease of hydrocarbon abundance and absence of some light components in pyrolysis gas chromatogram, and the decrease of fluorescence area and intensity from fluorescence logging. According to crude oil types, the cross plots of S1 versus peak-baseline ratio, and the cross plots of rock wettability versus fluorescence area ratio are drawn and used to interpret reservoir fluid property. Meanwhile, the standards of reservoir fluid parameter are established combining with the parameters of PS and the parameters in above charts, and comprehensive multiparameter correlation in both vertical and horizontal ways is also performed to interpret reservoir fluid property. The application in the Doseo Basin achieved great success, improving interpretation ability of fluid property in the reservoir with complex oil-water contact, and also provided technical reference for the efficient exploration and development of similar reservoirs.

Purpose: This study aimed to compare the effects on muscle hypertrophy and muscular performance of two resistance training (RT) programs that differed only in set structure: traditional set structure (TS) vs. rest redistribution set structure (RR).Methods: Thirty untrained young men were pair-matched and randomly assigned to a TS (n = 15) or an RR (n = 15) protocol based on individual baseline measures. Participants trained for 8 weeks using the same total body RT routines performed twice weekly. The TS protocol comprised four sets of 10 repetitions per exercise with 120-s interset rest, and the RR involved eight sets of five repetitions per exercise with 51-s interset rest. Participants were tested pre- and post-intervention for body composition, regional muscle thickness, upper- and lower-body muscle maximal strength [1-repetition maximum (1RM)], mean power output and velocity at 75% 1RM and muscular endurance (repetitions to failure at 70% 1RM).Results: Compared to baseline, both groups exhibited equally significantly decreased body fat mass (p < 0.05), increased fat-free mass (p < 0.001), muscle thickness (p < 0.05), upper and lower-body muscular maximal strength (p < 0.001) and endurance performance (p < 0.001). However, both groups only increase the lower-body power output (p < 0.001) but not the upper-body (p > 0.05). No significant differences existed between groups for all measurements (p > 0.05).Conclusion: These results suggest that RR and TS groups have similar effects for improving muscle hypertrophy and performance in untrained young men.

Supercritical CO2 has wide application in enhancing oil recovery, but the low viscosity of liquid CO2 can lead to issues such as poor proppant-carrying ability and high filtration loss. Therefore, the addition of thickening agents to CO2 is vital. Hydrocarbon polymers, as a class of green and sustainable materials, hold tremendous potential for acting as thickeners in supercritical CO2 systems, and PVAc is one of the best-performing hydrocarbon thickeners. To further improve the viscosity enhancement and solubility of PVAc, here we designed a novel polymer structure, PVAO, by introducing CO2-affine functional groups to PVAc. Molecular dynamics simulations were adopted to analyze viscosity and relevant solubility parameters systematically. We found that PVAO exhibits superior performance, with a viscosity enhancement of 1.5 times that of PVAc in supercritical CO2. While in the meantime, PVAO maintains better solubility characteristics than PVAc. Our findings offer insights for the future design of other high-performance polymers.

Sika deer are known to prefer oak leaves, which are rich in tannins and toxic to most mammals; however, the genetic mechanisms underlying their unique ability to adapt to living in the jungle are still unclear. In identifying the mechanism responsible for the tolerance of a highly toxic diet, we have made a major advancement by explaining the genome of sika deer. We generated the first high-quality, chromosome-level genome assembly of sika deer and measured the correlation between tannin intake and RNA expression in 15 tissues through 180 experiments. Comparative genome analyses showed that the UGT and CYP gene families are functionally involved in the adaptation of sika deer to high-tannin food, especially the expansion of the UGT family 2 subfamily B of UGT genes. The first chromosome-level assembly and genetic characterization of the tolerance to a highly toxic diet suggest that the sika deer genome may serve as an essential resource for understanding evolutionary events and tannin adaptation. Our study provides a paradigm of comparative expressive genomics that can be applied to the study of unique biological features in non-model animals.

The measurement of hemoglobin is a vital index for diagnosing and monitoring diseases in clinical practice. At present, solutions need to be found for the soreness, high risk of infection, and inconvenient operation associated with invasive detection methods. This paper proposes a method for non-invasively detecting hemoglobin levels based on multi-wavelength photoplethysmography (PPG) signals. AFE4490 and TMUX1109 were used to implement the low-cost collection of an eight-LED transmissive PPG signal. We used seven regular LEDs and one broadband LED (Osram SFH4737) as light sources. Additionally, a finger clip integrating multiple sensors was designed and manufactured via 3D printing to simultaneously monitor the LED–sensor distance and the pressure from the tester’s finger during PPG signal acquisition. We used a method to extract features from PPG signals using a sliding-window’s variance and an evaluation metric for PPG signals based on the AdaCost classification. Data were gathered from 56 participants from the Nephrology department, including 16 anemic patients. Pearson correlation analysis was conducted on the collected data to remove any data with a weak correlation. The advantage of using a broadband LED as a light source was also demonstrated. Several non-invasive hemoglobin regression models were created by applying AdaBoost, BPNN, and Random Forest models. The study’s results indicate that the AdaBoost model produced the best performance, with a mean absolute error (MAE) of 2.67 g/L and a correlation coefficient (R2) of 0.91 The study results show that the device we designed and manufactured can achieve effective non-invasive hemoglobin detection and represents a new methodological approach to obtaining measurements that can be applied in a clinical setting.

Background Previous results provide supportive but not conclusive evidence for the use of omega‐3 fatty acids to reduce blood lipids and prevent events of atherosclerotic cardiovascular disease, but the strength and shape of dose–response relationships remain elusive. Methods and Results This study included 90 randomized controlled trials, reported an overall sample size of 72 598 participants, and examined the association between omega‐3 fatty acid (docosahexaenoic acid, eicosapentaenoic acid, or both) intake and blood lipid changes. Random‐effects 1‐stage cubic spline regression models were used to study the mean dose–response association between daily omega‐3 fatty acid intake and changes in blood lipids. Nonlinear associations were found in general and in most subgroups, depicted as J‐shaped dose–response curves for low‐/high‐density lipoprotein cholesterol. However, we found evidence of an approximately linear dose–response relationship for triglyceride and non‐high‐density lipoprotein cholesterol among the general population and more evidently in populations with hyperlipidemia and overweight/obesity who were given medium to high doses (>2 g/d). Conclusions This dose–response meta‐analysis demonstrates that combined intake of omega‐3 fatty acids near linearly lowers triglyceride and non‐high‐density lipoprotein cholesterol. Triglyceride‐lowering effects might provide supportive evidence for omega‐3 fatty acid intake to prevent cardiovascular events.

Abstract. Background:. Worldwide, the volume and availability of digestive endoscopy have undergone dramatic development in recent years, with increasing attention on quality assurance. We investigated the utilization and quality of digestive endoscopy in China from 2015 to 2019 and developed a quantitative quality evaluation tool for medical institutions. Methods:. We invited all tertiary/secondary hospitals in Chinese mainland to participate in the survey annually. The questionnaires included the personnel, annual volume, and quality indicators of endoscopy. An endoscopy quality index (EQI) was developed based on recorded quality indicators using principal component analysis to determine the relative weight. Results:. From 2015 to 2019, 806, 1412, 2644, 2468, and 2541 hospitals were respectively enrolled in this study. The average annual volume of endoscopy increased from 12,445 to 16,206 (1.30-fold) and from 2938 to 4255 (1.45-fold) in tertiary and secondary hospitals, respectively. The most obvious growth was observed in diagnostic colonoscopy (1.44-fold for all hospitals after standardization). The proportion of early cancer among all esophageal and gastric cancers during diagnostic esophagogastroduodenoscopy increased from 12.3% (55,210/448,861) to 17.7% (85,429/482,647) and from 11.4% (69,411/608,866) to 16.9% (107,192/634,235), respectively. The adenoma detection rate of diagnostic colonoscopy increased from 14.9% (2,118,123/14,215,592) to 19.3% (3,943,203/20,431,104). The EQI model included 12 quality indicators, incorporating 64.9% (7.792/12) of the total variance into one comprehensive index. According to the EQI measurements, the quality of endoscopy was higher in tertiary hospitals and hospitals in developed areas with higher volume or more endoscopists than that in other hospitals. Conclusions:. Digestive endoscopy in China has developed considerably in recent years in terms of both volume and quality. The EQI is a promising tool to quantify the quality of endoscopy at different hospitals.

The study of learning behaviors with multi features is of great significance for interactive cooperation. The data prediction and decision are to realize the comprehensive analysis and value mining. In this study, hierarchical learning behavior based on feature cluster is proposed. Based on the massive data in interactive learning environment, the descriptive model and learning algorithm suitable for feature clustering are designed, and sufficient experiments obtain the optimal performance indexes. The data analysis results are reliable. On this basis, the hierarchical learning behaviors based on feature clusters are visualized, the rules of different learning behaviors are summarized, then we propose the practical scheme of interactive cooperation. The hierarchical learning behaviors can be realized by feature clusters, which can effectively improve the modes of interactive cooperation, and help to improve the learning effectiveness.

PurposeTo assess the effect of combination therapy with 3% diquafosol tetrasodium (DQS) and sodium hyaluronate (HA) for dry eye after femtosecond laser-assisted in situ keratomileusis (FS-LASIK).DesignProspective nonrandomized comparative trial.MethodsThe prospective study included 80 eyes of 40 patients who underwent FS-LASIK with or without preoperative dry eye. Patients were divided into a combination group and a HA group according to their willingness and the doctor’s advice. The combination group was treated with DQS six times a day and HA four times a day, and the HA group was treated with HA four times a day after FS-LASIK. Ocular surface disease index (OSDI), ocular symptom score, vision-related score, environmental score, tear meniscus height (TMH), first non-invasive tear breakup time (NIBUT-First), average non-invasive tear breakup time (NIBUT-Ave), tear breakup time (TBUT), Schirmer I test (SIT), corneal fluorescein staining score (CFS), bulbar redness score, limbal redness score, lipid layer grade (LLG), meiboscore, lid margin abnormality, corneal sensitivity, and corneal nerve parameters were examined before surgery and at 1 week and 1 month after surgery. Surface regularity index (SRI) was also examined before surgery and at 1 month postoperatively.ResultsOSDI score (p = 0.024) and vision-related score (p = 0.026) were significantly lower in the combination group than in the HA group at 1 month after FS-LASIK, especially in patients with preoperative dry eye symptoms. The increasements of CFS (p = 0.018), bulbar redness score (p = 0.021), and limbal redness score (p = 0.009) were significantly lower in the combination group than in the HA group at 1 week after FS-LASIK. But other ocular surface parameters showed no difference between both groups at 1 week and 1 month after FS-LASIK. LLG was significantly higher in the combination group than in the HA group at 1 week (p = 0.004) and 1 month (p

(1) Background: Preservatives may pose a potential threat to human health. To ensure food safety, this study has devised a method that concurrently detects a dozen preservatives (acetic acid, propionic acid, dehydroacetic acid, benzoic acid, sorbic acid, dimethyl fumarate, methyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, isopropyl parahydroxybenzoate, butyl parahydroxybenzoate, and isobutyl parahydroxybenzoate) in pastry, utilizing gas chromatography–mass spectrometry. (2) Methods: The pastry samples were acidified with hydrochloric acid, extracted with acetonitrile via vortexing, purified by hexane and saturated with sodium chloride solution to remove lipids and impurities, and then concentrated via nitrogen blowing. The method was then quantitatively analyzed using GC-MS with the internal standard method after methanol re-dissolution. (3) Results: The results showed that the content of the 12 preservatives had good linearity within the range of 1.0–50 μg/mL, with correlation coefficients all greater than 0.99. The method detection limit was 0.04–2.00 mg/kg and the quantification limit was 0.12–6.67 mg/kg. The average recovery rates of the samples at three different spiked concentrations of low, medium, and high were 70.18–109.22%, and the relative standard deviations were 1.82–9.79% (n = 6). (4) Conclusions: This method requires a small amount of sample, has high sensitivity, and is simple and fast to operate, making it suitable for the simultaneous determination of 12 preservatives in pastry. This approach contributes to the effective surveillance and regulation of preservative usage in pastries, thereby safeguarding public well-being.

Purpose – Francois Quesnay, known as the “Confucius of Europe”, was profoundly influenced by traditional Chinese culture to form his thoughts, which contained strong Chinese characteristics. This paper aims to examine economic thought of Francois Quesnay from the perspective of the construction of socialist political economics with Chinese characteristics. Design/methodology/approach – Moreover, his thoughts also profoundly influenced subsequent economists, such as Adam Smith and Karl Marx. It can be said that Francois Quesnay was at the intersection of Chinese, Western and Marxist thought systems, so it is quite important to examine his thoughts critically and conduct source-tracing in China. Findings – Hence, in the process of constructing and developing socialist political economy with Chinese characteristics, there is an urgent need to focus on exploring the value of excellent traditional Chinese culture at the theoretical level and combining the development and dissemination of the history of thoughts and the historical position of Chinese reality to realize the innovation and development of socialist political economy with Chinese characteristics. Originality/value – Meanwhile, while absorbing nutrition from excellent traditional Chinese culture, it is necessary to establish scientific coordinates rather than use the discourse systems and paradigms of Western economics to interpret ancient Chinese economic thoughts. It is necessary to adhere to, inherit and develop Marxist political economy and absorb nutrition from Chinese excellent traditional culture to construct socialist political economy with Chinese characteristics.

Here the authors report single-nucleus RNA sequencing for several anatomical locations in 11 species, including cat, dog, hamster, lizard, goat, rabbit, duck, pigeon, pangolin, tiger, and deer, highlighting coexpression of SARS-CoV-2 entry factors ACE2 and TMPRSS2.

Abstract Transfer RNA (tRNA)-derived small RNAs (tsRNAs), a novel category of small noncoding RNAs, are enzymatically cleaved from tRNAs. Previous reports have shed some light on the roles of tsRNAs in the development of human diseases. However, our knowledge about tsRNAs is still relatively lacking. In this paper, we review the biogenesis, classification, subcellular localization as well as action mechanism of tsRNAs, and discuss the association between chemical modifications of tRNAs and the production and functions of tsRNAs. Furthermore, using immunity, metabolism, and malignancy as examples, we summarize the molecular mechanisms of tsRNAs in diseases and evaluate the potential of tsRNAs as new biomarkers and therapeutic targets. At the same time, we compile and introduce several resource databases that are currently publicly available for analyzing tsRNAs. Finally, we discuss the challenges associated with research in this field and future directions.

Shape memory polymers (SMPs) are currently one of the most attractive smart materials expected to replace traditional shape memory alloys and ceramics (SMAs and SMCs, respectively) in some fields because of their unique properties of high deformability, low density, easy processing, and low cost. As one of the most popular SMPs, shape memory polyurethane (SMPU) has received extensive attention in the fields of biomedicine and smart textiles due to its biocompatibility and adjustable thermal transition temperature. However, its laborious synthesis, limitation to thermal response, poor conductivity, and low modulus limit its wider application. In this work, biocompatible poly(ε-caprolactone) diol (PCL-2OH) is used as the soft segment, isophorone diisocyanate (IPDI) is used as the hard segment, and glycerol (GL) is used as the crosslinking agent to prepare thermoset SMPU with a thermal transition temperature close to body temperature for convenient medical applications. The effects of different soft-chain molecular weights and crosslinking densities on the SMPU’s properties are studied. It is determined that the SMPU has the best comprehensive performance when the molar ratio of IPDI:PCL-2OH:GL is 2:1.5:0.33, which can trigger shape memory recovery at body temperature and maintain 450% recoverable strain. Such materials are excellent candidates for medical devices and can make great contributions to human health.

Nematodes are one of the largest groups of animals on the planet. Many of them are major pathogens of humans, animals and plants, and cause destructive diseases and socioeconomic losses worldwide. Despite their adverse impacts on human health and agriculture, nematodes can be challenging to control, because anthelmintic treatments do not prevent re-infection, and excessive treatment has led to widespread drug resistance in nematode populations. Indeed, many nematode species of livestock animals have become resistant to almost all classes of anthelmintics used. Most efforts to develop commercial anti-nematode vaccines (native or recombinant) for use in animals and humans have not succeeded, although one effective (dead) vaccine (Barbervax) has been developed to protect animals against one of the most pathogenic parasites of livestock animals – Haemonchus contortus (the barber’s pole worm). This vaccine contains native molecules, called H11 and H-Gal-GP, derived from the intestine of this blood-feeding worm. In its native form, H11 alone consistently induces high levels (75-95%) of immunoprotection in animals against disease (haemonchosis), but recombinant forms thereof do not. Here, to test the hypothesis that post-translational modification (glycosylation) of H11 plays a crucial role in achieving such high immunoprotection, we explored the N-glycoproteome and N-glycome of H11 using the high-resolution mass spectrometry and assessed the roles of N-glycosylation in protective immunity against H. contortus. Our results showed conclusively that N-glycan moieties on H11 are the dominant immunogens, which induce high IgG serum antibody levels in immunised animals, and that anti-H11 IgG antibodies can confer specific, passive immunity in naïve animals. This work provides the first detailed account of the relevance and role of protein glycosylation in protective immunity against a parasitic nematode, with important implications for the design of vaccines against metazoan parasites.

While existing studies have explored factors that affect knowledge sharing among employees from different perspectives, there are still research gaps regarding whether health belief affects knowledge sharing among employees, specifically against the backdrop of the COVID-19 pandemic, and how such effects work. Thus, the purpose of this study is to determine the effect of bank employees’ health beliefs about COVID-19 on knowledge sharing mediated by their self-efficacy. From the perspective of social cognitive theory and the health belief model, this study investigates whether employees’ perception of susceptibility and severity of COVID-19 affects formal as well as informal knowledge sharing through knowledge sharing self-efficacy. A sample of 407 bank employees (200 women and 207 men) in China was used for the study. The formulated hypotheses were tested using structural equation modeling and bootstrapping. The results showed that employees’ perceived susceptibility to COVID-19 significantly undermines formal and informal knowledge sharing self-efficacy. However, there was no significant difference in the extent of its indirect effects on formal and informal knowledge sharing. Further, employees’ perceived severity of COVID-19 had no effect on knowledge sharing self-efficacy and on formal and informal knowledge sharing, which could have resulted from the COVID-19 outbreak in China.

Myeloproliferative neoplasms (MPNs) are associated with significant alterations in the bone marrow microenvironment that include decreased expression of key niche factors and myelofibrosis. Here, we explored the contribution of TGF-β to these alterations by abrogating TGF-β signaling in bone marrow mesenchymal stromal cells. Loss of TGF-β signaling in Osx-Cre–targeted MSCs prevented the development of myelofibrosis in both MPLW515L and Jak2V617F models of MPNs. In contrast, despite the absence of myelofibrosis, loss of TGF-β signaling in mesenchymal stromal cells did not rescue the defective hematopoietic niche induced by MPLW515L, as evidenced by decreased bone marrow cellularity, hematopoietic stem/progenitor cell number, and Cxcl12 and Kitlg expression, and the presence of splenic extramedullary hematopoiesis. Induction of myelofibrosis by MPLW515L was intact in Osx-Cre Smad4fl/fl recipients, demonstrating that SMAD4-independent TGF-β signaling mediates the myelofibrosis phenotype. Indeed, treatment with a c-Jun N-terminal kinase (JNK) inhibitor prevented the development of myelofibrosis induced by MPLW515L. Together, these data show that JNK-dependent TGF-β signaling in mesenchymal stromal cells is responsible for the development of myelofibrosis but not hematopoietic niche disruption in MPNs, suggesting that the signals that regulate niche gene expression in bone marrow mesenchymal stromal cells are distinct from those that induce a fibrogenic program.

Augmented reality (AR) is a potentially disruptive technology that enriches the consumer experience and transforms marketing. With the surging popularity of AR in marketing practice, academic efforts to investigate its effects on consumer experience, response, and behavior have increased significantly. To obtain an integrated and comprehensive view of the front-line in AR marketing research and identify the gaps for future research, we analyze the existing AR marketing literature through a systematic literature review. Using 99 journal articles selected from the Web of Science core collections, this research sheds light on the general characteristics such as publication year, publication outlet, research design, and research method. Moreover, this research also gains insight into the AR marketing relevant factors such as application area, application context, AR type, and theoretical lenses. The findings of the analyses reveal the state-of-the-art of scholarly publications on AR marketing research. First, the number of journal articles on AR marketing increased rapidly in the past few years, and the journals that published articles on AR marketing cover a wide range of disciplines. Second, the empirical studies in most literature adopted the quantitative research design and used survey or experiment methods. Third, the studies in more than half of the journal articles used mobile AR applications in various online contexts. Fourth, the Technology Acceptance Model (TAM) and the Stimulus-Organism-Response (S-O-R) framework are the two most widely used theoretical lenses used in the literature. After that, the major application areas of AR in marketing are retail, tourism, and advertising. To identify the focal themes discussed in the three application areas, this research summarizes the studies by the outcome variables. Specifically, the outcome variables have five categories: technology-related, product-related, brand-related, tourist destination-related, and advertisement-related. Finally, this research proposes the agenda for future academic efforts in AR marketing.

The equine herpesvirus type 8 (EHV-8) can cause significant economic losses in the global horses and donkey industry. The disease has been associated with abortion and respiratory symptoms. However, it is rare for a study to be reported about donkeys with neurological diseases induced by EHV-8 infection. In the present study, one 2-year-old male donkey, from a large-scale donkey farm in China, died with a severe neurological disorder. The causative agent, donkey/Shandong/10/2021 (GenBank accession: OL856098), was identified and isolated from the brain tissue of the dead donkey. Meanwhile, BALB/c mice were used as an animal model to evaluate the pathogenicity of the EHV-8 isolate. Our data showed that EHV-8 was positive in brains by PCR and immunohistochemistry, which induced typical viral encephalitis lesions in both donkey and mice consistent with clinical signs. For the first time, we reported that EHV-8 had been isolated from donkeys with a neurological illness in China, which is helpful to reveal the pathogenicity of EHV-8 in the donkey.

In this work, we studied the evolution of vacancy-like defects and the formation of brittle precipitates in a reduced-activation V−Cr−Mn medium-entropy alloy. The evolution of local electronic circumstances around Cr and Mn enrichments, the vacancy defects, and the CrMn3 precipitates were characterized by using scanning electron microscopy with energy-dispersive spectroscopy, X-ray diffraction, and positron annihilation spectroscopy. The microstructure measurements showed that the Mn and Cr enrichments in the as-cast sample significantly evolved with temperature, i.e., from 400 °C, the Cr/Mn-segregated regions gradually dissolved into the matrix and then disappeared, and from 900 °C to 1000 °C, they existed as CrMn3 precipitates. The crystallite size of the phase corresponding to CrMn3 precipitates was about 29.4 nm at 900 °C and 43.7 nm at 1000 °C. The positron annihilation lifetime results demonstrated that the vacancies mediated the migration of Cr and Mn, and Cr and Mn segregation finally led to the formation of CrMn3 precipitates. The coincidence Doppler broadening results showed that the characteristic peak moved to the low-momentum direction, due to an increase in the size of the vacancy defects at the interface and the formation of CrMn3 precipitates.

The effects of biological factors on the vegetative growth process of mushrooms remain largely unexplored. We investigated the bacterial community in different growth stages of Pleurotus eryngii by high-throughput sequencing technology to explore the relationship between interacting bacteria and the growth and development of P. eryngii. We found significant variances in mushroom interacting association bacteria (MIAB) compositions among the samples from different growth stages, and 410 genera were identified. The bacteria in the full-bag and post-ripe stages were shifted to the biocontrol and growth-promotion ones. The mushroom growth-promoting bacteria (MGPB) were also isolated successfully and identified as B. cereus Bac1. The growth speed and density of mycelial pellets of P. eryngii, and activities of two exoenzymes (laccase and amylase), were analyzed by adding the different volumes of cell-free fermentation broth of B. cereus Bac1 to fungal culture media. The results showed that when a 5 mL cell-free fermentation broth was used, the growth speed of P. eryngii hyphae was enhanced by 1.15-fold over the control and reached 0.46 mm/h. The relative activity of laccase and amylase was increased by 26.9 and 43.83%. Our study revealed that the abundant interacting bacteria coexist with P. eryngii hyphae. Moreover, the abundance of some bacteria exhibiting a positive correlation with the growth periods of their host fungi can effectively promote the growth of the host, which will provide technical supports on the high-efficiency production of P. eryngii in factory cultivation.

Efficient provision of Video-on-Demand (VoD) services requires that popular videos are stored in a cache close to users. Video popularity (defined by requested count) prediction is, therefore, important for optimal choice of videos to be cached. The popularity of a video depends on many factors and, as a result, changes dynamically with time. Accurate video popularity estimation that can promptly respond to the variations in video popularity then becomes crucial. In this paper, we analyze a method, called Minimal Inverted Pyramid Distance (MIPD), to estimate a video popularity measure called the Inverted Pyramid Distance (IPD). MIPD requires choice of a parameter, k representing the number of past requests from each video used to calculate its IPD. We derive, analytically, expressions to determine an optimal value for k, given the requirement on ranking a certain number of videos with specified confidence. In order to assess the prediction efficiency of MIPD, we have compared it by simulations against four other prediction methods: Least Recency Used (LRU), Least Frequency Used (LFU), Least Recently/Frequently Used (LRFU), and Exponential Weighted Moving Average (EWMA). Lacking real data, we have, based on an extensive literature review of real-life VoD system, designed a model of VoD system to provide a realistic simulation of videos with different patterns of popularity variation, using the Zipf (heavy-tailed) distribution of popularity and a non-homogeneous Poisson process for requests. From a large number of simulations, we conclude that the performance of MIPD is, in general, superior to all of the other four methods.

Gut microbiome dysbiosis has been known to be associated with all stages of non-alcoholic fatty liver disease (NAFLD), but questions remain about microbial profiles in progression and homogeneity across NAFLD stages. We performed a meta-analysis of three publicly shotgun datasets and built predictive models to determine diagnostic capacity. Here, we found consistently microbiome shifts across NAFLD stages, of which co-occurrence patterns and core sets of new biomarkers significantly correlated with NAFLD progression were identified. Machine learning models that are able to distinguish patients with any NAFLD stage from healthy controls remained predictive when applied to patients with other NAFLD stages, suggesting the homogeneity across stages once again. Focusing on species and metabolic pathways specifically associated with progressive stages, we found that increased toxic metabolites and decreased protection of butyrate and choline contributed to advanced NAFLD. We further built models discriminating one stage from the others with an average of 0.86 of area under the curve. In conclusion, this meta-analysis firmly establishes generalizable microbiome dysbiosis and predictive taxonomic and functional signatures as a basis for future diagnostics across NAFLD stages.

PurposeColon cancer (CC) is a serious disease burden. The prognosis of patients with CC is different, so looking for effective biomarkers to predict prognosis is vitally important. Ferroptosis is a promising therapeutic and diagnosis strategy in CC. However, the role of ferroptosis in prognosis of CC has not been studied. The aim of the study is to build a prognosis model related ferroptosis, and provide clues for further therapy of CC.MethodsThe RNA-seq data were from TCGA (training group) and GEO (testing group). The R language and Perl language were used to process and analyze data. LASSO regression analysis was used to build the prognosis model. ssGSEA was used to compare the immune status between two groups. Immunohistochemistry was used to detect expression of AKR1C1 and CARS1 in colon cancer tissues and adjacent tissues.ResultsThe prognosis model consisted of five ferroptosis related genes (AKR1C1, ALOX12, FDFT1, ATP5MC3, and CARS1). The area under curve (AUC) at 1-, 2-, and 3-year were 0.668, 0.678, and 0.686, respectively. The high- and low-risk patients had significant survival probability and could be clearly distinguished by the PCA and t-SNE analysis. The multivariate cox regression analysis also showed the riskscore is an independent prognosis factor. Importantly, we found that the immune status between high- and low-risk patients were different obviously, such as CD8+T cells. And STING, a new promising immune target, was also correlated to our signature genes statistically significantly.ConclusionOur ferroptosis prognosis signature could predict survival of CC patients to a certain degree. And the crosstalk between ferroptosis and immune, especially STING need further studies.

Background: Abnormal construction of the extracellular matrix (ECM) is intimately linked with carcinogenesis and the development of solid tumours, especially hepatocellular carcinoma (HCC). As the major component of the ECM, collagen plays a pivotal role in carcinogenesis. P4HA2, the essential enzyme during collagen formation, becomes an important target in HCC treatment. Here, we tried to decipher whether aspirin (ASA), a classic anti-inflammatory drug, could improve the prognosis of HCC through targeting P4HA2. Methods: Western blotting, qRT-PCR assay, immunofluorescence staining, luciferase reporter gene assay, and ChIP assay were applied to demonstrate the molecular mechanism of the regulation of P4HA2 expression by aspirin. A mouse xenograft model, cell viability assay, colony formation assay, and immunohistochemistry analysis were used to evaluate the anti-fibrosis effect of aspirin through targeting the NF-κB/P4HA2 axis and LMCD1-AS1/let-7g/P4HA2 axis in vitro and in vivo. The TCGA database was used to evaluate the correlation among P4HA2, let-7g, LMCD1-AS1 and overall survival of HCC patients. Findings: In xenograft mice, aspirin was capable of targeting P4HA2 to decrease collagen deposition, resulting in the inhibition of liver tumour growth. TCGA database analysis revealed the close association between a higher P4HA2 concentration in HCC patients and shorter overall survival or a higher cancer stage and the pathological grade. Mechanistically, NF-κB can bind to the promoter of P4HA2 to activate its transcription. Moreover, lncRNA LMCD1-AS1 functions as a molecular sponge of let-7g to post-transcriptionally induce the target gene of let-7g, namely, P4HA2. Interpretation: Our findings disclose the novel role and regulatory mechanism of aspirin in the suppression of HCC by disrupting abnormal collagen deposition. Funds: 973 Program, National Natural Scientific Foundation of China, Fundamental Research Funds for the Central Universities, Project of Prevention and Control of Key Chronic Non-Infectious Diseases. Keywords: Aspirin, P4HA2, NF-κB, LMCD1-AS1, Let-7g, Collagen deposition

Abstract Background Previous investigations of phylogeny in Cervus recovered many clades without whole genomic support. Methods In this study, the genetic diversity and phylogeny of 5 species (21 subspecies/populations from C. unicolor, C. albirostris, C. nippon, C. elaphus and C. eldii) in the genus Cervus were analyzed using reduced-representation genome sequencing. Results A total of 197,543 SNPs were identified with an average sequencing depth of 16 x. A total of 21 SNP matrices for each subspecies/population and 1 matrix for individual analysis were constructed, respectively. Nucleotide diversity and heterozygosity analysis showed that all 21 subspecies/populations had different degrees of genetic diversity. C. eldii, C. unicolor and C. albirostris showed relatively high expected and observed heterozygosity, while observed heterozygosity in C. nippon was the lowest, indicating there was a certain degree of inbreeding rate in these subspecies/populations. Phylogenetic ML tree of all Cervus based on the 21 SNP matrices showed 5 robustly supported clades that clearly separate C. eldii, C. unicolor, C. albirostris, C. elaphus and C. nippon. Within C. elaphus clade, 4 subclades were well differentiated and statistically highly supported: C. elaphus (New Zealand), C. e. yarkandensis, C. c. canadensis and the other grouping the rest of C. canadensis from China. In the C. nippon clade, 2 well-distinct subclades corresponding to C. n. aplodontus and other C. nippon populations were separated. Phylogenetic reconstruction indicated that the first evolutionary event of the genus Cervus occurred approximately 7.4 millions of years ago. The split between C. elaphus and C. nippon could be estimated at around 3.6 millions of years ago. Phylogenetic ML tree of all samples based on individual SNP matrices, together with geographic distribution, have shown that there were 3 major subclades of C. elaphus and C. canadensis in China, namely C. e. yarkandensis (distributed in Tarim Basin), C. c. macneilli/C. c. kansuensis/C. c. alashanicus (distributed in middle west of China), and C. c. songaricus/C. c. sibiricus (distributed in northwest of China). Among them, C. e. yarkandensis was molecularly the most primitive subclade, with a differentiation dating back to 0.8–2.2 Myr ago. D statistical analysis showed that there was high probability of interspecific gene exchange between C. albirostris and C. eldii, C. albirostris and C. unicolor, C. nippon and C. unicolor, and there might be 2 migration events among 5 species in the genus Cervus. Conclusions Our results provided new insight to the genetic diversity and phylogeny of Cervus deer. In view of the current status of these populations, their conservation category will need to be reassessed.

Background/Aims: HER2 has been implicated in mammary tumorigenesis as well as aggressive tumor growth and metastasis. Its overexpression is related to a poor prognosis and chemoresistance in breast cancer patients. Although Grb2-associated binding protein 2 (Gab2) is important in the development and progression of human cancer, its effects and mechanisms in HER2-overexpressing breast cancer are unclear. Methods: Clone formation and MTT assays were used to examine cell proliferation. To detect the effect of Gab2 on the stemness of breast cancer cells, we used flow cytometry, a sphere formation assay, real-time PCR, and western blot. An animal model was created to validate the effect of Gab2 on tumor growth in vivo. Tissue slides were analyzed by immunohistochemistry. Results: Knockdown of Gab2 suppressed PI3K/AKT and MAPK/ERK pathway activity. Gab2 ablation also reduced the stemness of HER2-overexpressing breast cancer cells. In vivo, knockdown of Gab2 inhibited tumor growth. Conclusion: This study unveils a potential function of Gab2 in HER2-overexpressing breast cancer cells. Gab2 might be a potential target in the clinical therapy of HER2-overexpressing breast carcinoma.

Bright crescent areas were obviously apparent at the bottom of melt pools of Inconel 718 samples prepared by selective laser melting (SLM). Their microstructure, composition, spatial morphology, and mechanical behaviors were systematically investigated. These areas consisted of finer columnar dendrites with underdeveloped secondary arms, which resulted in a bright color under optical field and dark color under SEM. Both growth and crystal orientations were consistent with those of the grains in the melt pool of the former layer. Enrichment of elements Nb and Ti occurred among the dendrites in these areas, leading to the formation of Laves phases. The crescent areas underwent great deformation together with the melt pools during tensile testing, which showed that they were of great plasticity and no gaps or cracks were found around these areas. In addition, the bright crescent areas possessed higher hardness than that of the surrounding regions. Furthermore, the simulated temperature field results showed that the incomplete re-melting of the formed dendrites and a large number of nucleated dendrites among them are the main reasons for the formation of the bright crescent areas.

Abstract Infection is a common cause of morbidity and mortality in chronic lymphocytic leukemia and should be considered when examining bone marrow specimens to identify a potentially treatable pathogen.

Abstract Background The Zc3h8 gene encodes a protein with three zinc finger motifs in the C-terminal region. The protein has been identified as a component of the Little Elongation Complex, involved in transcription of small nuclear RNAs. ZC3H8 is overexpressed in a number of human and mouse breast cancer cell lines, and elevated mRNA levels are associated with a poorer prognosis for women with breast cancer. Methods We used RNA silencing to decrease levels of expression in mouse mammary tumor cells and overexpression of ZC3H8 in cells derived from the normal mouse mammary gland. We measured characteristics of cell behavior in vitro, including proliferation, migration, invasion, growth in soft agar, and spheroid growth. We assessed the ability of these cells to form tumors in syngeneic BALB/c mice. ZC3H8 protein was visualized in cells using confocal microscopy. Results Tumor cells with lower ZC3H8 expression exhibited decreased proliferation rates, slower migration, reduced ability to invade through a basement membrane, and decreased anchorage independent growth in vitro. Cells with lower ZC3H8 levels formed fewer and smaller tumors in animals. Overexpression of ZC3H8 in non-tumorigenic COMMA-D cells led to an opposite effect. ZC3H8 protein localized to both PML bodies and Cajal bodies within the nucleus. ZC3H8 has a casein kinase 2 (CK2) phosphorylation site near the N-terminus, and a CK2 inhibitor caused the numerous PML bodies and ZC3H8 to coalesce to a few larger bodies. Removal of the inhibitor restored PML bodies to their original state. A mutant ZC3H8 lacking the predicted CK2 phosphorylation site showed localization and numbers of ZC3H8/PML bodies similar to wild type. In contrast, a mutant constructed with a glutamic acid in place of the phosphorylatable threonine showed dramatically increased numbers of smaller nuclear foci. Conclusions These experiments demonstrate that Zc3h8 expression contributes to aggressive tumor cell behavior in vitro and in vivo. Our studies show that ZC3H8 integrity is key to maintenance of PML bodies. The work provides a link between the Little Elongation Complex, PML bodies, and the cancer cell phenotype.

Abstract Background Resistance to tamoxifen (TAM) frequently occurs in the treatment of estrogen receptor positive (ER+) breast cancer. Accumulating evidences indicate that transcription factor HOXB13 is of great significance in TAM resistance. However, the regulation of HOXB13 in TAM-resistant breast cancer remains largely unexplored. Here, we were interested in the potential effect of HBXIP, an oncoprotein involved in the acceleration of cancer progression, on the modulation of HOXB13 in TAM resistance of breast cancer. Methods The Kaplan-Meier plotter cancer database and GEO dataset were used to analyze the association between HBXIP expression and relapse-free survival. The correlation of HBXIP and HOXB13 in ER+ breast cancer was assessed by human tissue microarray. Immunoblotting analysis, qRT-PCR assay, immunofluorescence staining, Co-IP assay, ChIP assay, luciferase reporter gene assay, cell viability assay, and colony formation assay were performed to explore the possible molecular mechanism by which HBXIP modulates HOXB13. Cell viability assay, xenograft assay, and immunohistochemistry staining analysis were utilized to evaluate the effect of the HBXIP/HOXB13 axis on the facilitation of TAM resistance in vitro and in vivo. Results The analysis of the Kaplan-Meier plotter and the GEO dataset showed that mono-TAM-treated breast cancer patients with higher HBXIP expression levels had shorter relapse-free survivals than patients with lower HBXIP expression levels. Overexpression of HBXIP induced TAM resistance in ER+ breast cancer cells. The tissue microarray analysis revealed a positive association between the expression levels of HBXIP and HOXB13 in ER+ breast cancer patients. HBXIP elevated HOXB13 protein level in breast cancer cells. Mechanistically, HBXIP prevented chaperone-mediated autophagy (CMA)-dependent degradation of HOXB13 via enhancement of HOXB13 acetylation at the lysine 277 residue, causing the accumulation of HOXB13. Moreover, HBXIP was able to act as a co-activator of HOXB13 to stimulate interleukin (IL)-6 transcription in the promotion of TAM resistance. Interestingly, aspirin (ASA) suppressed the HBXIP/HOXB13 axis by decreasing HBXIP expression, overcoming TAM resistance in vitro and in vivo. Conclusions Our study highlights that HBXIP enhances HOXB13 acetylation to prevent HOXB13 degradation and co-activates HOXB13 in the promotion of TAM resistance of breast cancer. Therapeutically, ASA can serve as a potential candidate for reversing TAM resistance by inhibiting HBXIP expression.

Gansu wapiti (Cervus elaphus kansuensis) is one of eight subspecies of wapiti in China, which has been placed under the second-ranked protected animals by Chinese government. No complete mitochondrial genomes of Gansu wapiti was determined until now, so the phylogenetic relationships among the subspecies of wapiti and other species of the genus Cervus have not been well studied. In this study, the complete mitochondrial genome of C. e. kansuensis was first sequenced and characterized. The genome is 16,430 bp in length, containing 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, two ribosomal RNA (rRNA) genes, and one noncoding control region (CR). Maximum-Likelihood (ML) and Bayesian Inference (BI) trees based on the 13 PCGs show that C. e. kansuensis is clustered with other wapiti subspecies in China except for C. e. yarkandensis. It is also shown that Cervus elaphus is not a monophyletic group. This study provides important molecular evidence for the phylogenetic relationship among species in the genus Cervus.

The artificial intelligence methods might be applied to see through the education problems, and make effective prediction and decision. The transformation from data to decision are inseparable from the learning analytics. In order to solve the dynamic multi-objective decision problems, a decision learning algorithm is designed to analyze the learning behavior and learning achievement based on the particle swarm optimization mechanism, which ensures the global optimization of data analysis. Compared with the performance indicators of several approximate algorithms, this algorithm has the advantage of association analysis, which improves the accuracy and robustness; Furthermore, three tested problems are constructed by GeoDa tool, and through data training and analysis, the dynamic multi-objective decision rules are obtained. The whole research can provide theoretical and technical support for other related or similar issues.

Abstract Growing evidences showed that a large number of miRNAs were abnormally expressed in cervical cancer tissues and played irreplaceable roles in tumorigenesis, progression and metastasis. The aim of the present study was to identify the differential miRNAs expression between cervical cancer and normal cervical tissues by analyzing the high-throughput miRNA data downloaded from TCGA database. Additionally, we evaluated the prognostic values of the differentially expressed miRNAs and constructed a three-miRNA signature that could effectively predict patient survival. According to the cut-off criteria (P 2.0), a total of 78 differentially expressed miRNAs were identified between cervical cancer tissues and matched normal tissues, including 37 up-regulated miRNAs and 41 down-regulated miRNAs. The Kaplan-Meier survival method revealed the prognostic function of the three miRNAs (miRNA-145, miRNA-200c, and miRNA-218-1). Univariate and multivariate Cox regression analysis showed that the three-miRNA signature was an independent prognostic factor in cervical cancer. The functional enrichment analysis suggested that the target genes of three miRNAs may be involved in various pathways related to cancer, including MAPK, AMPK, focal adhesion, cGMP-PKG, wnt, and mTOR signaling pathway. Taken together, the present study suggested that three-miRNA signature could be used as a prognostic marker in cervical cancer.

Abstract In the present study, two elongases, Elovl4 and Elovl5, were functionally characterized and their transcriptional regulation in response to n-3 LC-PUFA administration were investigated in vivo and in vitro. We previously described the molecular characterization of croaker elovl5. Here, we report the full-length cDNA sequence of croaker elovl4, which contained 1794 bp (excluding the polyA tail), including 909 bp of coding region that encoded a polypeptide of 302 amino acids possessing all the characteristic features of Elovl proteins. Functional studies showed that croaker Elovl5, displayed high elongation activity towards C18 and C20 PUFA, with only low activity towards C22 PUFA. In contrast, croaker Elovl4 could effectively convert both C20 and C22 PUFA to longer polyenoic products up to C34. n-3 LC-PUFA suppressed transcription of the two elongase genes, as well as srebp-1 and lxrα, major regulators of hepatic lipid metabolism. The results of dual-luciferase reporter assays and in vitro studies both indicated that the transcriptions of elovl5 and elovl4 elongases could be regulated by Lxrα. Moreover, Lxrα could mediate the transcription of elovl4 directly or indirectly through regulating the transcription of srebp-1. The above findings contribute further insight and understanding of the mechanisms regulating LC-PUFA biosynthesis in marine fish species.

Selective laser melting (SLM) is a promising powder bed fusion additive manufacturing technique for metal part fabrication. In this paper, varying scanning speed in the range of 500 mm/s to 1900 mm/s, and laser power in the range of 100 W to 200 W, were realized from layer to layer in a cycle of 56 layers in a single cuboid Inconel 718 alloy specimen through SLM. Layer-wise variation of microstructure and porosity were acquired, showing the layer-wise controlling capability of microstructural soundness. The melt pool size and soundness are closely linked with the energy input. High energy density led to sound regions with larger, orderly stacked melt pools and columnar grains, while low energy density resulted in porous regions with smaller, mismatched melt pools, un-melted powder, and equiaxed grains with finer dendrites. With the increase of laser energy density, the specimen shifts from porous region to sound region within several layers.

The enzymes involved in the biosynthesis of long-chain polyunsaturated fatty acids (LC-PUFAs) are widely studied in fish species, as fish are the main source of n-3 LC-PUFAs for human beings. In the present study, a putative gene for elovl5, which encodes a key enzyme involved in LC-PUFA synthesis, was cloned and functionally characterized, and its transcription in response to dietary n-3 LC-PUFA exposure was investigated. Moreover, cell transfection and luciferase assays were used to explore the mechanism underlying the regulation of elovl5. The full-length cDNA of elovl5 was 1242 bp (excluding the polyA tail), including an 885 bp coding region encoding a 295 amino acid protein that possesses all of the characteristic features of elovl proteins. Functional characterization of heterologously expressed grouper Elovl5 indicated that it effectively elongates both C18 (18:2n-6, 18:3n-3, 18:3n-6 and 18:4n-3) and C20 (20:4n-6 and C20:5n-3) PUFAs, but not the C22 substrates. The expression of elovl5 was significantly affected by dietary n-3 LC-PUFA exposure: a high n-3 LC-PUFA level repressed the expression of elovl5 by slightly down-regulating the expression of sterol regulatory element-binding protein (SREBP)-1 and liver X receptor (LXR) α, which are major regulators of hepatic lipid metabolism. Promoter studies showed that grouper elovl5 reporter activity was induced by over-expression of LXRα but not SREBP-1. This finding suggests that elovl5 is a direct target of LXRα, which is involved in the biosynthesis of PUFAs via transcriptional regulation of elovl5. These findings may contribute to a further understanding of the mechanism underlying the regulation of LC-PUFA biosynthesis in marine fish species.