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Abstract Receptor Expression-Enhancing Protein 3 (REEP3) serves as a pivotal enzyme crucial for endoplasmic reticulum (ER) clearance during mitosis and is implicated in the advancement of diverse malignancies. Nonetheless, the biological role and mechanisms of REEP3 in pancreatic cancer patients, along with its interplay with immune infiltration, remain inadequately elucidated. In this study, we initially analyzed the differential expression of REEP3 between pancreatic cancer tissues and normal pancreas tissues using the Cancer Genome Atlas (TCGA), GTEx and Gene Expression Omnibus (GEO) databases. Subsequently, we utilized Kaplan–Meier analysis, Cox regression and ROC curve to determine the predictive value of REEP3 for the clinical outcomes of pancreatic cancer patients. Functional enrichment analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA), were conducted to explore the potential signaling pathways and biological functions associated with pancreatic cancer. Furthermore, we investigated the PPI network, miRNA, RBP and transcription factor interactions of REEP3 using databases such as GeneMania, STRING, StarBase, KnockTK, ENCODE, Jaspar and hTFtarget. Lastly, the “ssGSEA” algorithm and TIMER database were employed to investigate the correlation between REEP3 expression and immune infiltration as well as immune checkpoints. The expression of REEP3 in pancreatic cancer showed a significantly higher level compared to that in normal tissues. ROC curve analysis indicated that REEP3 holds substantial diagnostic potential for pancreatic cancer patients. Elevated REEP3 expression correlated with unfavorable outcomes in terms of both overall survival and relapse-free survival, establishing it as a notable adverse prognostic marker in pancreatic cancer. Moreover, both univariate and multivariate Cox regression analyses demonstrated that REEP3 maintained an independent association with overall survival. Functional enrichment analyses revealed pathways significantly linked to REEP3, including cytoplasmic translation, wound healing, viral processes, regulation of cellular component size and actin filament organization. Additionally, REEP3 expression displayed a significant positive correlation with CD8+ T cells, B cells, natural killer cells, dendritic cells and macrophages. REEP3 is a potential diagnostic, prognostic marker and immunotherapeutic target for pancreatic cancer.

Abstract To study the characteristics of nasal airflow in the presence of nasal cycle by computational fluid dynamics. CT scan data of a healthy Chinese individual was used to construct a three-dimensional model of the nasal cavity to be used as simulation domain. A sinusoidal airflow velocity is set at the nasal cavity entrance to reproduce the breathing pattern of a healthy human. There was a significant difference in the cross-sectional area between the two sides of the nasal cavity. Particularly, the decongested side is characterized by a larger cross-section area, and consequently, by a larger volume with respect to the congested side. The airflow velocity, pressure, and nasal resistance were higher on the congested narrow side. The temperature regulation ability on the congested narrow side was stronger than that on the decongested wider side. During the nasal cycle, there are differences in the nasal cavity function between the congested and decongested sides. Therefore, when evaluating the impact of various factors on nasal cavity function, the nasal cycle should be considered.

Abstract This study aimed to investigate the probable existence of a causal relationship between sleep phenotypes and proliferative diabetic retinopathy (PDR). Single nucleotide polymorphisms associated with sleep phenotypes were selected as instrumental variables at the genome-wide significance threshold (P

Abstract The damage to the endocrine pancreas among patients with diseases of the exocrine pancreas (DP) leads to reduced glycemic deterioration, ultimately resulting in diabetes of the exocrine pancreas (DEP). The present research aims to investigate the mechanism responsible for glycemic deterioration in DP patients, and to identify useful biomarkers, with the ultimate goal of enhancing clinical practice awareness. Gene expression profiles of patients with DP in this study were acquired from the Gene Expression Omnibus database. The original study defines DP patients to belong in one of three categories: non-diabetic (ND), impaired glucose tolerance (IGT) and DEP, which correspond to normoglycemia, early and late glycemic deterioration, respectively. After ensuring quality control, the discovery cohort included 8 ND, 20 IGT, and 12 DEP, while the validation cohort included 27 ND, 15 IGT, and 20 DEP. Gene set enrichment analysis (GSEA) employed differentially expressed genes (DEGs), while immunocyte infiltration was determined using single sample gene set enrichment analysis (ssGSEA). Additionally, correlation analysis was conducted to establish the link between clinical characteristics and immunocyte infiltration. The least absolute shrinkage and selection operator regression and random forest combined to identify biomarkers indicating glycemic deterioration in DP patients. These biomarkers were further validated through independent cohorts and animal experiments. With glycemic deterioration, biological processes in the pancreatic islets such as nutrient metabolism and complex immune responses are disrupted in DP patients. The expression of ACOT4, B2M, and ACKR2 was upregulated, whereas the expression of CACNA1F was downregulated. Immunocyte infiltration in the islet microenvironment showed a significant positive correlation with the age, body mass index (BMI), HbA1c and glycemia at the 2-h of patients. It was a crucial factor in glycemic deterioration. Additionally, B2M demonstrated a significant positive correlation with immunocyte infiltration and clinical features. Quantitative real-time PCR (qRT-PCR) and western blotting confirmed the upregulation in B2M. Immunofluorescent staining suggested the alteration of B2M was mainly in the alpha cells and beta cells. Overall, the study showed that gradually increased immunocyte infiltration was a significant contributor to glycemic deterioration in patients with DP, and it also highlighted B2M as a biomarker.

Abstract The violent goods vibration during curve negotiation is a huge threat to the vehicle running safety. Qualified load restraint assemblies that can significantly suppress the cargo vibration are necessary. This study proposes a novel method for evaluating the essential restraint strength, focusing on the relative motion between cargo and wagon. In the beginning, as a comparison, current methods are used to calculate the necessary stiffness of lashings, which are adopted to restrain the cargo vibration on the wagon. Based on the data of the field test, the accuracy of the established wagon-cargo coupled dynamics model is validated. The loaded wagon model negotiates the curve under different running and loading conditions. The simulation results and analysis demonstrate effective strategies for suppressing the vibration of the cargo and reveal the necessary lashing stiffness. The comparison among the results of different evaluation methods shows that the stability of the cargo can be improved by optimizing the lashing stiffness with the method of dynamics simulations. We hope this study will make a positive contribution to the safety of railway freight transportation.

Abstract Ambient pollutants, particularly fine particulate matter (PM2.5) and ozone (O3), pose significant risks to both public health and economic development. In recent years, PM2.5 concentration in China has decreased significantly, whereas that of O3 has increased rapidly, leading to considerable health risks. In this study, a generalized additive model was employed to establish the relationship of PM2.5 and O3 exposure with non-accidental mortality across 17 districts and counties in Jilin Province, China, over 2015–2016. The health burden and economic losses attributable to PM2.5 and O3 were assessed using high-resolution satellite and population data. According to the results, per 10 µg/m3 increase in PM2.5 and O3 concentrations related to an overall relative risk (95% confidence interval) of 1.004 (1.001–1.007) and 1.009 (1.005–1.012), respectively. In general, the spatial distribution of mortality and economic losses was uneven. Throughout the study period, a total of 23,051.274 mortalities and 27,825.015 million Chinese Yuan (CNY) in economic losses were attributed to O3 exposure, which considerably surpassing the 5,450.716 mortalities and 6,553,780 million CNY in economic losses attributed to PM2.5 exposure. The O3-related health risks and economic losses increased by 3.75% and 9.3% from 2015 to 2016, while those linked to PM2.5 decreased by 23.33% and 18.7%. Sensitivity analysis results indicated that changes in pollutant concentrations were the major factors affecting mortality rather than baseline mortality and population.

Abstract Herein, a novel Ag NP substrate doped with Au nanobipyramids was designed and fabricated via a convenient procedure of galvanic reaction for the identification and classification of amphetamine-type stimulants (ATS) in oral fluids in combination with surface enhanced Raman scattering (SERS). The substrate was shown to have a three-dimensional nanostructure, high SERS activity, and good stability. In combination with SERS, the Ag NP substrate doped with Au nanobipyramids was able to detect ultra-low traces of ATS, including amphetamine, methylamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA), and 3,4-methylenedioxymethylamphetamine (MDMA) in oral fluid with limit of detection (LOD) and limit of determination quantitation (LOQ) as low as 10–9 mg/mL, which is much better than the current spectroscopic techniques. The equations between concentration and peaks intensity for quantitative analysis displied good doublelogarithmic linear relations and reliability figures of merit at nanogram concentration level in compartion with GC–MS method. The approach can be broadly applied to the ultra-low trace detection of ATS in oral fluid and would be particularly useful for the analyses of nitrogenous organic compounds.

Abstract A novel trajectory tracking strategy is developed for a double actuated swing in a hydraulic construction robot. Specifically, a nonlinear hydraulic dynamics model of a double actuated swing is established, and a parameter adaptive sliding mode control strategy is designed to enhance the trajectory tracking performance. When an object is grabbed and unloaded, the moment of inertia of a swing considerably changes, and the performance of the estimation algorithm is generally inadequate. Thus, it is necessary to establish an algorithm to identify the initial value of the moment of inertia of the object. To this end, this paper proposes a novel initial value identification algorithm based on a two-DOF robot gravity force identification method combined with stereo vision information. The performance of the identification algorithm is enhanced. Simulations and experiments are performed to verify the effect of the novel control scheme.

Abstract The L-shell x-ray emissions of gold are investigated for the bombardment of high energy C6+ ions in the high energy region of 154.3–423.9 MeV/u. Due to the multiple ionization of outer-shell electrons at the movement of L x-ray emission, the blue shift of the experimental x-ray energy and an enhancement of the relative intensity ratios of Lι, Lβ–Lα x rays are observed. Using the improved thin target formula and considering the effect of multiple ionization on atomic parameters, the L-subshell x-ray production cross sections are extracted from the counts and compared with the theoretical estimations of BEA, PWBA and ECPSSR. It is found that the relative corrections of ECPSSR on PWBA can be ignored in the present experimental energy region. The calculations of PWBA and ECPSSR are almost identical and both are larger than the experimental results. The BEA is in better agreement with the experiment as a whole.

Abstract Rheumatoid arthritis (RA) is chronic systemic disease that can cause joint damage, disability and destructive polyarthritis. Current diagnosis of RA is based on a combination of clinical and laboratory features. However, RA diagnosis can be difficult at its disease onset on account of overlapping symptoms with other arthritis, so early recognition and diagnosis of RA permit the better management of patients. In order to improve the medical diagnosis of RA and evaluate the effects of different clinical features on RA diagnosis, we applied an artificial neural network (ANN) as the training algorithm, and used fivefold cross-validation to evaluate its performance. From each sample, we obtained data on 6 features: age, sex, rheumatoid factor, anti-citrullinated peptide antibody (CCP), 14-3-3η, and anti-carbamylated protein (CarP) antibodies. After training, this ANN model assigned each sample a probability for being either an RA patient or a non-RA patient. On the validation dataset, the F1 for all samples by this ANN model was 0.916, which was higher than the 0.906 we previously reported using an optimal threshold algorithm. Therefore, this ANN algorithm not only improved the accuracy of RA diagnosis, but also revealed that anti-CCP had the greatest effect while age and anti-CarP had a weaker on RA diagnosis.

Abstract Since the outbreak of the 2019 Coronavirus disease (COVID-19) at the end of 2019, it has caused great adverse effects on the whole world, and it has been hindering the global economy. It is ergent to establish an infectious disease model for the current COVID-19 epidemic to predict the trend of the epidemic. Based on the SEIR model, the improved SEIR models were established with considering the incubation period, the isolated population, and genetic algorithm (GA) parameter optimization method. The improved SEIR models can predict the trend of the epidemic situation better and obtain the more accurate epidemic-related parameters. Comparing some key parameters, it is capable to evaluate the impact of different epidemic prevention measures and the implementation of different epidemic prevention levels on the COVID-19, which has significant guidance for further epidemic prevention measures.

Abstract The L-shell X-ray emissions of iodine are investigated as a function of the incident energy for I22+ ions impacting on Fe target in the energy region near the Bohr velocity. Six distinct L-subshell X-rays, Lι, Lα1, 2, Lβ1, 3, 4, Lβ2, 15, Lγ1 and Lγ2, 3, 4, 4 ', are observed. Compared to the atomic data, the energy of the experimental X ray shifts to the higher energy side. The relative intensity ratios of Lι, Lβ1, 3, 4, Lβ2, 15, to Lα1, 2, Lι to Lβ2, 15 and Lγ2, 3, 4, 4/ to Lγ1 are enhanced, but has no obvious change with the increase of projectile energy in the present energy region. That is interpreted by the multiple ionization effect of the M-, N- and O-shell electrons.

Abstract Bushen-Tiaojing-Fang (BSTJF) is commonly used to treat infertility. This study investigated the effects of BSTJF on the pregnancy outcomes of patients with repeated controlled ovarian stimulation (COS), on mitochondrial function, and on oxidative stress in ovarian granulosa cells (GCs) and follicular fluid (FF). The samples and clinical data of 97 patients, including 35 in the control group, 29 in the placebo group and 33 in the BSTJF group, were collected for this study. The mitochondrial ultrastructure, ATP content, mitochondrial DNA (mtDNA) number, 8-hydroxy-2-deoxyguanosine (8-OHdG), Mn-superoxide dismutase (Mn-SOD), glutathione peroxidase (GSH-Px) activity levels, and mRNA expression levels of Mn-SOD, GSH-Px, and nuclear factor erythroid-derived factor 2-related factor 2 (Nrf2) were analyzed. The high-grade embryo (P

Abstract To retrospectively analyze the use of artificial pneumoperitoneum in CT scans, to explore its operation methods and technical points, and to lay the foundation for the widespread application of artificial pneumoperitoneum in CT. A total of 331 patients who underwent artificial pneumoperitoneum with CT angiography from January 1, 2013, to November 1, 2019, were recruited. All patients underwent standardized artificial pneumoperitoneum in the horizontal, left and right lateral, and prone positions during CT thin-layer scans of the abdomen and 3D reconstruction. Taking the surgical results as the gold standard, and using kappa test to verify the consistency of surgical results and imaging results. In all 331 patients, 43 patients had a normal peritoneal space, and 288 patients had an abnormal peritoneal space. And only 22 patients developed complications of subcutaneous emphysema, accounting for 6.6% of all 331 patients. In terms of the postoperative results, 28 were normal, and 303 were abnormal. The sensitivity, specificity and accuracy of CT diagnosis of abdominal adhesions using artificial pneumoperitoneum were 100%, 95.04%, and 95.46%, respectively. According to the Kappa consistency test, the imaging diagnosis from the CT scan with artificial pneumoperitoneum had a high consistency with the surgical results (kappa = 0.796, P

Abstract To develop a tool for predicting pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (neoCRT) in patients with esophageal cancer by combining inflammatory status and tumor glucose metabolic activity. This study included 127 patients with locally advanced esophageal cancer who had received neoCRT followed by esophagectomy from 2007 to 2016. We collected their neutrophil–lymphocyte ratio (NLR) and standardized uptake value (SUV) obtained from fluorodeoxyglucose positron emission tomography (PET/CT) before and after neoCRT. Univariate and multivariate logistic regression analyses were performed to identify potential predictive factors for pCR. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of predictors were calculated. Between pCR and non-pCR groups, there were no statistically significant differences in patient characteristics, such as sex, age, site, and clinical T/N stage. Multivariate analyses identified four independent predictors for pCR, including pre-OP NLR 7.2 [OR 3.033; 95% CI 1.354–6.791; p = 0.007], and SUV changes ratio (ΔSUV ratio) > 58% [OR 3.585; 95% CI 1.576–8.152; p = 0.002]. ΔNLR had the highest accuracy and NPV (84.3% and 90.3%, respectively). Combined factors of ΔNLR 58% had the best PPV for pCR (84.8%). Inflammatory status (ΔNLR) and tumor glucose metabolic activity (ΔSUV ratio), when considered together, constitute a promising low-invasive tool with high efficacy for prediction of treatment response before surgery.

Abstract Anaerobic ammonium oxidation (anammox) plays an important role in aquatic systems as a sink of bioavailable nitrogen (N), and in engineered processes by removing ammonium from wastewater. The isotope effects anammox imparts in the N isotope signatures (15N/14N) of ammonium, nitrite, and nitrate can be used to estimate its role in environmental settings, to describe physiological and ecological variations in the anammox process, and possibly to optimize anammox-based wastewater treatment. We measured the stable N-isotope composition of ammonium, nitrite, and nitrate in wastewater cultivations of anammox bacteria. We find that the N isotope enrichment factor 15ε for the reduction of nitrite to N2 is consistent across all experimental conditions (13.5‰ ± 3.7‰), suggesting it reflects the composition of the anammox bacteria community. Values of 15ε for the oxidation of nitrite to nitrate (inverse isotope effect, − 16 to − 43‰) and for the reduction of ammonium to N2 (normal isotope effect, 19–32‰) are more variable, and likely controlled by experimental conditions. We argue that the variations in the isotope effects can be tied to the metabolism and physiology of anammox bacteria, and that the broad range of isotope effects observed for anammox introduces complications for analyzing N-isotope mass balances in natural systems.

Abstract Ten new polyoxygenated cyathane diterpenoids, named neocyathins A–J (1–10), together with four known diterpenes (11–14), were isolated from the liquid culture of the medicinal basidiomycete fungus Cyathus africanus. The structures and configurations of these new compounds were elucidated through comprehensive spectroscopic analyses including 1D NMR, 2D NMR (HSQC, HMBC, NOESY) and HRESIMS, and electronic circular dichroism (ECD) data. Neuroinflammation is implicated in the pathogenesis of various neurodegenerative diseases, such as Alzheimers’ disease (AD). All isolated compounds were evaluated for the potential anti-neuroinflammatory activities in BV2 microglia cells. Several compounds showed differential effects on the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated and Aβ1–42-treated mouse microglia cell line BV-2. Molecular docking revealed that bioactive compounds (e.g., 11) could interact with iNOS protein other than COX-2 protein. Collectively, our results suggested that this class of cyathane diterpenoids might serve as important lead compounds for drug discovery against neuroinflammation in AD.

Abstract Plasma dipeptidyl-peptidase-4 activity (DPP4a) is inversely associated with left ventricular function in patients with heart failure (HF) or diabetes. However, the association between DPP4a and left ventricular function in ST-segment elevation myocardial infarction (STEMI) patients has not been reported. We studied this association in 584 consecutive STEMI patients at a tertiary referral center from July 2014 to October 2015. DPP4a and plasma N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) levels were quantified by enzymatic assays. The median serum NT-proBNP levels were highest in patients of the lowest tertile (T1) of DPP4a compared with that of the highest tertile (T3) (p = 0.028). The STEMI patients in T1 exhibited lower left ventricular systolic function (T1 vs. T3: left ventricular ejection fraction (LVEF): 50.13 ± 9.12 vs. 52.85 ± 6.82%, p = 0.001). Multivariate logistic-regression analyses (adjusted for confounding variables) showed that a 1 U/L increase in DPP4a was associated with a decreased incidence of left ventricular systolic dysfunction (LVSD) (adjusted odds ratio: 0.90; 95% CI: 0.87–0.94; p

Abstract West Nile virus (WNV) is a neurotropic pathogen which causes zoonotic disease in humans. Recently, there have been an increasing number of infected cases and there are no clinically approved vaccines or effective drugs to treat WNV infections in humans. The purpose of this study was to facilitate vaccine and antiviral drug discovery by developing a packaging cell line-restricted WNV infectious replicon particle system. We constructed a DNA-based WNV replicon lacking the C-prM-E coding region and replaced it with a GFP coding sequence. To produce WNV replicon particles, cell lines stably-expressing prM-E and C-prM-E were constructed. When the WNV replicon plasmid was co-transfected with a WNV C-expressing plasmid into the prM-E-expressing cell line or directly transfected the C-prM-E expressing cell line, the replicon particle was able to replicate, form green fluorescence foci, and exhibit cytopathic plaques similar to that induced by the wild type virus. The infectious capacity of the replicon particles was restricted to the packaging cell line as the replicons demonstrated only one round of infection in other permissive cells. Thus, this system provides a safe and convenient reporter WNV manipulating tool which can be used to study WNV viral invasion mechanisms, neutralizing antibodies and antiviral efficacy.

Abstract We studied the molecular epidemiology and mechanism of azole resistance of 164 C. guilliermondii isolates from a nationwide multi-center surveillance program. The isolates were identified by ITS gene sequencing, and the in vitro susceptibility to fluconazole and voriconazole was determined by broth microdilution method. The 14-α-demethylase gene ERG11 was amplified and sequenced, and microsatellite analysis was performed to study the genetic relatedness of the isolates. Amongst the 164 C. guilliermondii isolates, 15 (9.1%) and 17 (10.4%) isolates were assigned to be non-wild type (non-WT) to fluconazole and voriconazole, respectively. Sixteen sequence types (STs) were detected by comparing the amino acid sequence polymorphisms of the ERG11 gene. Fifteen isolates of STs 9, 10, 12, 13, 14, 15 and 16, were all assigned to be non-WT to fluconazole and voriconazole. By microsatellite analysis, 40 different genotypes were identified. Thirty-seven isolates from one hospital (Z1) shared the same ERG11 sequence type (ST 2), microsatellite genotype (PU40) and drug resistance pattern. In conclusion, this is the first molecular epidemiology study of C. guilliermondii in China. The rate of non-WT isolates to azoles was high and the accurate contribution of ERG11 gene mutations to azole resistance need be confirmed by further studies.