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Abstract Background The spleen plays a critical role in the immune response against malaria parasite infection, where splenic fibroblasts (SFs) are abundantly present and contribute to immune function by secreting type I collagen (collagen I). The protein family is characterized by Plasmodium vivax tryptophan-rich antigens (PvTRAgs), comprising 40 members. PvTRAg23 has been reported to bind to human SFs (HSFs) and affect collagen I levels. Given the role of type I collagen in splenic immune function, it is important to investigate the functions of the other members within the PvTRAg protein family. Methods Protein structural prediction was conducted utilizing bioinformatics analysis tools and software. A total of 23 PvTRAgs were successfully expressed and purified using an Escherichia coli prokaryotic expression system, and the purified proteins were used for co-culture with HSFs. The collagen I levels and collagen-related signaling pathway protein levels were detected by immunoblotting, and the relative expression levels of inflammatory factors were determined by quantitative real-time PCR. Results In silico analysis showed that P. vivax has 40 genes encoding the TRAg family. The C-terminal region of all PvTRAgs is characterized by the presence of a domain rich in tryptophan residues. A total of 23 recombinant PvTRAgs were successfully expressed and purified. Only five PvTRAgs (PvTRAg5, PvTRAg16, PvTRAg23, PvTRAg30, and PvTRAg32) mediated the activation of the NF-κBp65 signaling pathway, which resulted in the production of inflammatory molecules and ultimately a significant reduction in collagen I levels in HSFs. Conclusions Our research contributes to the expansion of knowledge regarding the functional role of PvTRAgs, while it also enhances our understanding of the immune evasion mechanisms utilized by parasites. Graphical Abstract

Background Pneumoconiosis mostly combines pulmonary and cardiovascular diseases, among which pulmonary heart disease (PHD) is of major concern due to its significant impact on the survival of pneumoconiosis patients. White cell count (WCC), red cell distribution width (RDW) and platelet parameters are thought to affect inflammatory responses and may be predictors of various cardiovascular diseases. However, very few studies have focused on PHD.Objectives To examine the relationship between baseline complete blood count parameters (WCC, RDW, platelet parameters) and the risk of incident PHD in pneumoconiosis patients.Design A retrospective cohort study.Setting This was a single-centre, retrospective cohort study that used data from an Occupational Disease Hospital, Chengdu, Sichuan.Participants A total of 946 pneumoconiosis patients from January 2012 to November 2021 were included in the study. Female patients and patients who had PHD, coronary heart disease, hypertensive heart disease, cardiomyopathy, heart failure, oncological disease, multiple organ dysfunction, AIDS at baseline and follow-up time of less than 6 months were also excluded.Outcome measures We identified PHD according to the patient’s discharge diagnosis. We constructed Cox proportional hazard regression models to assess the HR of incident PHD in pneumoconiosis, as well as 95% CIs.Results In the multiple Cox proportional hazard regression analysis, platelet count (PLT) and plateletcrit (PCT) above the median at baseline were associated with an increased risk of PHD in pneumoconiosis with adjusted HR of 1.52 (95% CI 1.09 to 2.12) and 1.42 (95% CI 1.02 to 1.99), respectively.Conclusion Higher baseline PLT and PCT are associated with a higher risk of PHD in pneumoconiosis.

AimsThe body roundness index (BRI) has good predictive ability for both body fat and visceral adipose tissue. Longitudinal BRI trajectories can reveal the potential dynamic patterns of change over time. This prospective study assessed potential associations between BRI trajectories and incident cardiovascular disease (CVD) in rural regions of Northeast China.MethodsIn total, 13,209 participants (mean age: 49.0 ± 10.3 years, 6,856 [51.9%] male) were enrolled with three repeated times of BRI measurements at baseline (2004–2006), 2008, and 2010, and followed up until 2017 in this prospective study. Using latent mixture model, the BRI trajectories were determined based on the data from baseline, 2008 and 2010. Composite CVD events (myocardial infarction, stroke, and CVD death combined) was the primary endpoint. Cox proportional-hazards models were used to analyze the longitudinal associations between BRI trajectories and incident CVD.ResultsThree distinct BRI trajectories were identified: high-stable (n = 538), moderate-stable (n = 1,542), and low-stable (n = 11,129). In total, 1,382 CVD events were recorded during follow-up. After adjustment for confounders, the moderate-stable and high-stable BRI groups had a higher CVD risk than did the low-stable BRI group, and the HR (95%CI) were 1.346 (1.154, 1.571) and 1.751 (1.398, 2.194), respectively. Similar associations were observed between the trajectories of BRI and the risk of stroke and CVD death. The high-stable group was also significantly and independently associated with CVD, myocardial infarction, stroke, and CVD death in participants aged

BackgroundClonorchis sinensis (C. sinensis) is a epidemiologically significant food-borne parasite, causing several hepatobiliary diseases. Biliary microbiota community structure might be influenced by infection with pathogens. However, the biliary microbiome of biliary obstruction patients infected with C. sinensis is still an unexplored aspect.MethodsA total of 50 biliary obstruction patients were enrolled, including 24 infected with C. sinensis and 26 non-infected subjects. The bile samples were collected by Endoscopic Retrograde Cholangiopancretography. Biliary microbiota alteration was analyzed through high-throughput 16S ribosomal RNA (rRNA) gene sequencing.ResultsOur findings revealed that there was significant increase in both richness and diversity, as well as changes in the taxonomic composition of the biliary microbiota of C. sinensis infected patients. At the phylum level, C. sinensis infection induced Proteobacteria increased and Firmicutes reduced. At the genus level, the relative abundance of Pseudomonas and Staphylococcus increased significantly, while Enterococcus decreased prominently in infected groups (P < 0.05). The PICRUSt analysis further showed remarkably different metabolic pathways between the two groups.ConclusionC. sinensis infection could modify the biliary microbiota, increasing the abundance and changing the phylogenetic composition of bacterial in biliary obstruction patients. This study may help deepen the understanding of the host-biliary microbiota interplay with C. sinensis infection on the background of biliary obstruction and provide new insights into understanding the pathogenesis of clonorchiasis.

BackgroundClonorchiasis is an important foodborne parasitic disease. However, eggs of Clonorchis sinensis (C. sinensis) cannot be detected in feces during biliary obstruction. Moreover, many diseases can cause biliary obstruction, such as gallstones, adenocarcinoma, cholangiocarcinoma and Ascaris lumbricoides infection. Therefore, it is of great significance to distinguish between patients of biliary obstruction and biliary obstruction with C. sinensis infection.MethodsA total of 48 biliary obstruction patients were enrolled, including 23 infected with C. sinensis (C. sinensis) (OB+C.s) and 25 non-infected subjects (OB). The bile samples were collected by endoscopic retrograde cholangiopancreatography and analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF MS). Additionally, multivariate statistical analysis methods were employed to identify differential metabolites. Next, bile amino acid levels were determined by targeted metabolomics analysis.ResultA total of 146 and 132 significant metabolites were identified in electrospray ionization (ESI)+ and ESI− modes, respectively. The levels of amino acids (asparagine, glutamate, ornithine) and polyamines (spermidine and spermine) were significantly changed. Targeted analysis showed that the levels of amino acids (such as L-arginine, L-glutamine, L-lysine, L-propionic, and L-tyrosine) were lower in OB+C.s patients compared to those in OB patients. Marked metabolic pathways were involved in “Glutathione metabolism”, “Caffeine metabolism”, “Alanine, aspartate and glutamate metabolism”, “Arginine and proline metabolism”, “Purine metabolism”, “Beta-Alanine metabolism”, and “D-glutamine and D-glutamate metabolism”.ConclusionThese results show that there were significant differences between OB+C.s and OB patients, especially in amino acids. The metabolic signature and perturbations in metabolic pathways may help to better distinguish OB+C.s and OB patients.

Patients with inborn errors of immunity (IEI) have been transplanted for more than 50 years. Many long-term survivors have ongoing medical issues showing the need for further improvements in how hematopoietic stem cell transplantation (HSCT) is performed if patients in the future are to have a normal quality of life. Precise genetic diagnosis enables early treatment before recurrent infection, autoimmunity and organ impairment occur. Newborn screening for severe combined immunodeficiency (SCID) is established in many countries. For newly described disorders the decision to transplant is not straight-forward. Specific biologic therapies are effective for some diseases and can be used as a bridge to HSCT to improve outcome. Developments in reduced toxicity conditioning and methods of T-cell depletion for mismatched donors have made transplant an option for all eligible patients. Further refinements in conditioning plus precise graft composition and additional cellular therapy are emerging as techniques to personalize the approach to HSCT for each patient

BackgroundClonorchiasis is an important foodborne parasitic disease. The omics-based-techniques could illuminate parasite biology and further make innovations in the research for parasitic diseases. However, knowledge about the serum metabolic profiles and related metabolic pathways in clonorchiasis is very limited.MethodsA untargeted ultra-high performance liquid tandem chromatography quadrupole time of flight mass spectrometry (UHPLC-QTOF-MS) was used to profile the serum metabolites of rats at both 4 and 8 weeks post infection (wpi) with Clonorchis sinensis (C. sinensis). Additionally, multivariate statistical analysis methods were employed to identify differential metabolites. Next, serum amino acids and phosphatidylcholines (PCs) levels were determined by targeted metabolomics analysis.ResultA total of 10530 and 6560 ions were identified in ESI+ and ESI− modes. The levels of phosphatidylcholines, glycerophosphocholine and choline were significantly changed, with the shift in lipid metabolism. Significant changes were also observed in amino acids (isoleucine, valine, leucine, threonine, glutamate and glutamine). Targeted analysis showed that BCAAs (isoleucine, valine, leucine) levels significantly increased at 4 wpi and decreased at 8 wpi; threonine was increased at 8 wpi, whereas glutamate and glutamine showed a decreasing trend at 8 wpi. Additionally, the level of 17 PCs were significantly changed in infected rats. Marked metabolic pathways were involved in clonorchiasis, including glycerophospholipid metabolism, alanine, aspartate and glutamate metabolism, histidine metabolism and pyrimidine metabolism.ConclusionThese results show that C. sinensis infection can cause significant changes in the rat serum metabolism, especially in amino acids and lipids. The metabolic signature together with perturbations in metabolic pathways could provide more in depth understanding of clonorchiasis and further make potential therapeutic interventions.

Abstract Recurrent gene mutations and fusions in cancer patients are likely to be associated with cancer progression or recurrence by Vogelstein et al. (Science (80-) 340, 1546–1558 (2013)). In this study, we investigated gene mutations and fusions that recurrently occurred in early-stage cancer patients with stage I non-small-cell cancer (NSCLC). Targeted exome sequencing was performed to profile the variants and confirmed their fidelity at the gene and pathway levels through comparison with data for stage I lung cancer patients, which was obtained from The Cancer Genome Atlas (TCGA). Next, we identified prognostic gene mutations (ATR, ERBB3, KDR, and MUC6), fusions (GOPC-ROS1 and NTRK1-SH2D2A), and VEGF signaling pathway associated with cancer recurrence. To infer the functional implication of the recurrent variants in early-stage cancers, the extent of their selection pattern was investigated, and they were shown to be under positive selection, implying a selective advantage for cancer progression. Specifically, high selection scores were observed in the variants with significantly high risks for recurrence. Taken together, the results of this study enabled us to identify recurrent gene mutations and fusions in a stage I NSCLC cohort and to demonstrate positive selection, which had implications regarding cancer recurrence.

Teacher emotions are essential for teaching effectiveness and teachers’ professional development. Studying teacher emotions during a program in today’s world is crucial, where teachers are commonly involved in professional development programs. From an ecological perspective, this study employed a case study method to examine the emotions of two Chinese high school mathematics teachers in a 4-year teaching improvement program. Semi-structured interviews, teacher emotion logs, researcher memos, and informal dialogues were all used to collect data. This study aimed to better understand the emotions that Chinese high school mathematics teachers developed and the processes that generated them in their interactions with various ecosystems within a specific professional development program overlay. The study’s findings revealed that the two teachers triggered 65 emotions in their interactions with the various ecosystems over 4 years—A describing 51 and B describing 46—with an overall predominance of positive emotions. They triggered the broadest range of emotions in the mesosystem, particularly during interactions with program companions. During the early, medium, and late stages, their internal psychological factors and interactions with each system changed, resulting in significant changes in their emotions. They all went through phases of mixed sadness and happiness, ending in a state of delight and calmness. Finally, we recommended teachers’ professional development based on the study’s findings.

Unfractionated heparin (UFH) is an anionic glycosaminoglycan that is widely used to prevent blood clotting. However, in certain cases, unwanted side effects can require it to be neutralized. Protamine sulfate (PS), a basic peptide rich in arginine, is the only approved antagonist for UFH neutralization. Many adverse reactions occur with the clinical application of PS, including systemic hypotension, pulmonary hypertension, and anaphylaxis. We previously described R15, a linear peptide composed of 15 arginine molecules, as a potential UFH antagonist. In this study, the in‐depth safety of R15 was explored to reveal its merits and associated risks in comparison with PS. In vitro safety studies investigated the interactions of R15 with erythrocytes, fibrin, complement, and rat plasma. In vivo safety studies explored potential toxicity and immunogenicity of R15 and the UFH–R15 complex. Results showed that both PS and R15 can induce erythrocyte aggregation, thicken fibrin fibers, activate complement, and cause anticoagulation in a concentration‐dependent manner. However, those influences weakened in whole blood or in live animals and were avoided when R15 was in a complex with UFH. We found dramatically enhanced complement activation when there was excess UFH in analyses involving UFH–PS complexes, and a slight increase in those involving UFH–R15 complexes. Within 2 h, R15 was degraded in rat plasma in vitro, whereas PS was not. Enhanced creatinine was found after a single intravenous injection of PS or R15 (900 U·kg−1, body weight), suggesting possible abnormal renal function. The UFH–PS complex, but not the UFH–R15 complex, exhibited obvious immunogenicity. In conclusion, R15 is nonimmunogenic and potentially safe at a therapeutic dose to reverse the effects of UFH.

BackgroundHeart failure (HF) is associated with generalized insulin resistance (IR). Recent studies demonstrated that triglyceride glucose (TyG) is an effective alternative index of IR. However, the relationship between the TyG index and in-hospital mortality in patients with HF is unclear. In the present study, we aimed to clarify the association between the TyG index and in-hospital mortality in patients with HF.MethodsA retrospective study consisting of 4,411 patients diagnosed with HF from 2015 to 2018 was conducted. All-cause mortality during hospitalization was the primary endpoint. The association between the TyG index and in-hospital mortality was assessed using the logistic regression analysis.ResultsThe risk of in-hospital mortality was significantly associated with increased TyG index (OR: 1.886, 95% CI: 1.421–2.501, p < 0.001) under logistic regression with multivariable adjustment. When divided into three groups based on the TyG index, Tertile 3 demonstrated significantly higher in-hospital mortality than the other two Tertiles (OR: 2.076, 95% CI: 1.284–3.354, p = 0.001). Moreover, the TyG index improved the prediction efficiency of the Get with the Guidelines-Heart Failure (GWTG-HF) score (absolute integrated discrimination improvement = 0.006, p < 0.001; category-free net reclassification improvement = 0.075, p = 0.005). In subgroup analysis, the TyG index exhibited similar predictive performance of in-hospital mortality when groups were stratified based on type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD).ConclusionTyG is a potential index for predicting in-hospital mortality in patients with HF, independent of T2DM or CAD status. The TyG index may be combined with the GWTG-HF score to further improve its predictive efficacy.

Griseofulvin was considered an effective agent for cancer therapy in past decades. Although the negative effects of griseofulvin on microtubule stability are known, the exact target and mechanism of action in plants remain unclear. Here, we used trifluralin, a well-known herbicide targeting microtubules, as a reference and revealed the differences in root tip morphology, reactive oxygen species production (ROS), microtubule dynamics, and transcriptome analysis between Arabidopsis treated with griseofulvin and trifluralin to elucidate the mechanism of root growth inhibition by griseofulvin. Like trifluralin, griseofulvin inhibited root growth and caused significant swelling of the root tip due to cell death induced by ROS. However, the presence of griseofulvin and trifluralin caused cell swelling in the transition zone (TZ) and meristematic zone (MZ) of root tips, respectively. Further observations revealed that griseofulvin first destroyed cortical microtubules in the cells of the TZ and early elongation zone (EZ) and then gradually affected the cells of other zones. The first target of trifluralin is the microtubules in the root MZ cells. Transcriptome analysis showed that griseofulvin mainly affected the expression of microtubule-associated protein (MAP) genes rather than tubulin genes, whereas trifluralin significantly suppressed the expression of αβ-tubulin genes. Finally, it was proposed that griseofulvin could first reduce the expression of MAP genes, meanwhile increasing the expression of auxin and ethylene-related genes to disrupt microtubule alignment in root tip TZ and early EZ cells, induce dramatic ROS production, and cause severe cell death, eventually leading to cell swelling in the corresponding zones and inhibition of root growth.

Fetal growth restriction (FGR) is the failure of the fetus toachieve its genetically determined growth potential, which increasesrisks for a variety of genetic diseases, such as type 2 diabetes mellitus, coronary artery disease, and stroke, during the lifetime. The dysregulation of DNA methylationis known to interact with environmental fluctuations, affect gene expressions comprehensively, and be fatal to fetus development in specific cases. Therefore, we set out to find out epigenetic and transcriptomic alterations associated with FGR development. We found a set of differentially expressed genes associated with differentially methylated regions in placentae and cord blood samples. Using dimensional reduction analysis, the expression and methylation variables of the epigenetically altered genes classified the FGR samples from the controls. These genes were also enriched in the biological pathways such as metabolism and developmental processes related to FGR. Furthermore, three genes of INS, MEG3, and ZFP36L2 are implicated in epigenetic imprinting, which has been associated with FGR. These results strongly suggest that DNA methylation is highly dysregulated during FGR development, and abnormal DNA methylation patterns are likely to alter gene expression.

Objective: Single-cell RNA sequencing (scRNA-seq) analyses have provided a novel insight into cell-specific gene expression changes in diseases. Here, this study was conducted to identify cell types and pathophysiologic factors in diabetic nephropathy.Methods: Single-cell RNA sequencing data of three human diabetic kidney specimens and three controls were retrieved from the GSE131882 dataset. Following preprocessing and normalization, cell clustering was presented and cell types were identified. Marker genes of each cell type were identified by comparing with other cell types. A ligand–receptor network analysis of immune cells was then conducted. Differentially expressed marker genes of immune cells were screened between diabetic nephropathy tissues and controls and their biological functions were analyzed. Diabetic nephropathy rat models were established and key marker genes were validated by RT-qPCR and Western blot.Results: Here, 10 cell types were clustered, including tubular cells, endothelium, parietal epithelial cells, podocytes, collecting duct, mesangial cells, immune cells, distal convoluted tubule, the thick ascending limb, and proximal tubule in the diabetic kidney specimens and controls. Among them, immune cells had the highest proportion in diabetic nephropathy. Immune cells had close interactions with other cells by receptor–ligand interactions. Differentially expressed marker genes of immune cells EIF4B, RICTOR, and PRKCB were significantly enriched in the mTOR pathway, which were confirmed to be up-regulated in diabetic nephropathy.Conclusion: Our findings identified immune cells and their marker genes (EIF4B, RICTOR, and PRKCB) as key pathophysiologic factors that might contribute to diabetic nephropathy progression.

AimsAbnormal thyroid hormone secretions can alter the manifestation and prognosis of cardiovascular disease. To assess the effect of the free triiodothyronine (FT3)/free thyroxine (FT4) ratio on the prognosis of patients with heart failure (HF), we performed a propensity-matched study on patients with well-balanced baseline characteristics.MethodsOverall, 8,887 patients with HF were divided into two groups according to the FT3/FT4 ratio. Propensity scores were calculated from each patient. A cohort comprising 2,164 pairs with high or low ratios and with 34 well-balanced baseline characteristics was then assembled. The endpoints were Cardiovascular (CV) mortality and all-cause mortality. The correlation between FT3/FT4 ratio and prognosis was assessed using matched Cox regression analyses. The mean follow-up was 3.3 years.ResultsIn the full pre-match cohort, 3,710 (41.7%) patients died, with 2,581 (29.0%) cases of CV mortality. In the matched-pair cohort, all-cause mortality occurred in 923 (1,238/10,000 person-years of follow-up) patients with a high ratio and 1,036 (1,484/10,000 person-years) patients with a low ratio, resulting in a matched HR of 0.841 (95% CI: 0.769–0.919; P < 0.001). For CV mortality, the result was 638 (856/10,000 person-years) and 714 (1,023/10,000 person-years) patients, respectively, resulting in a matched HR of 0.844 (95% CI: 0.759–0.940; P < 0.001). Subgroup analysis revealed that a low FT3/FT4 ratio had a greater predictive value for all-cause and CV mortality in elderly or male patients and in patients with coronary artery disease (CAD), hypertension, diabetes mellitus, HFmrEF, or HFpEF.ConclusionsA low FT3/FT4 ratio is valuable for predicting CV mortality and all-cause mortality in patients with HF.

A resistant muffler is the most direct and effective means of reducing exhaust noise from earthmoving equipment. Different types of construction machinery require different mufflers. Current muffler design is mostly experience-based, and there are blind spots in the design process. The optimization scheme must constantly be revised to achieve satisfactory noise reduction. The use of a large number of optimization schemes are wasteful in terms of both cost and time. Therefore, an effective and time-saving design method for muffler optimization is needed. An optimization approach, known as the “local structural optimization method for a resistant muffler”, based on orthogonal analysis is proposed in this study to optimize the design of a resistant muffler with a complex structure. The results of an orthogonal analysis for a simulation of the muffler structure show that the muffler acoustic and aerodynamic performances are affected by the inlet pipe, outlet pipe, insertion pipe, cross-flow perforated pipe and other local structures, and the results are employed to determine the influence law for the transmission loss (TL) and the exhaust back pressure, considering the local structural parameters of the muffler. The method is applied to optimize the design of a muffler suitable for an excavator and verified by performing an installation test. The experimental results show that the improved designs reduces the exhaust noise by 5 dB and the exhaust back pressure by 0.6 kPa. The improved designs exhibit higher aerodynamic and acoustic performances than a muffler prototype, showing that the proposed method is accurate, effective and reliable. The proposed method considerably simplifies the design process and saves time and cost. This method provides theoretical guidance and an optimization process for the design of a muffler for construction machinery.

Water environment pollution due to chemical spills occurs constantly worldwide. When a chemical accident occurs, a quick initial response is most important. In previous studies, samples collected from chemical accident sites were subjected to laboratory-based precise analysis or predictive research through modeling. These results can be used to formulate appropriate responses in the event of chemical accidents; however, there are limitations to this process. For the initial response, it is important to quickly acquire information on chemicals leaked from the site. In this study, pH and electrical conductivity (EC), which are easy to measure in the field, were applied. In addition, 13 chemical substances were selected, and pH and EC data for each were established according to concentration change. The obtained data were applied to machine learning algorithms, including decision trees, random forests, gradient boosting, and XGBoost (XGB), to determine the chemical substances present. Through performance evaluation, the boosting method was found to be sufficient, and XGB was the most suitable algorithm for chemical substance detection.

Three-dimensional (3D) graphene (Gr) has been successfully grown on a patterned sapphire substrate (PSS) with very low mismatch between Gr and the sapphire nanostructure through metal-catalyst-assisted chemical vapor deposition (CVD). However, the transfer of the 3D Gr film without compromising the structural integrity of Gr is challenging because of the low etching rate of PSS. For easy and high-quality transfer of 3D Gr, we propose to coat a transfer-support layer (TSL) on PSS before direct CVD growth of 3D Gr. The TSL is directly deposited on PSS by atomic layer deposition without causing any structural changes in the substrate, as verified through atomic force microscopy (AFM). Few-layer 3D Gr is conformally produced along the surface of the TSL/PSS and successfully transferred onto a flexible substrate through wet-etching transfer, as confirmed by scanning electron microscopy, AFM, and Raman spectroscopy studies. We also present the fabrication of a sensitive and flexible surface-enhanced Raman scattering sensor based on 3D Gr on PMMA with high detection performance for low concentrations of R6G (10−9 M). The proposed transfer method with TSL is expected to broaden the use of 3D graphene in next-generation device applications.

Clonorchiasis is recognized as an important zoonotic parasitic disease worldwide. However, the roles of host long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in the response to Clonorchis sinensis (C. sinensis) infection remain unknown. Here we compared the expression of lncRNAs and mRNAs in the liver tissue of mice infected with C. sinensis, in order to further understand the molecular mechanisms of clonorchiasis. A total of 388 lncRNAs and 1,172 mRNAs were found to be differentially expressed with absolute value of fold change (FC) ≥ 2.0 and p < 0.05 by microarray. Compared with controls, Gm6135 and 4930581F22Rik were the most over- and under-expressed lncRNAs; flavin-containing monooxygenase 3 (Fmo3) and deleted in malignant brain tumors 1 (Dmbt1) were the most over- and under-expressed mRNAs. Moreover, functional annotation showed that the significantly different mRNAs were related with “FOXO signaling pathway”, “Wnt signaling pathway”, and “AMPK signaling pathway”. Remarkably, lncRNA Gm8801 were significantly correlated with mRNA glycerol-3-phosphate acyltransferase mitochondrial (Gpam), insulin receptor substrate 2 (Irs2), and tumor necrosis factor receptor superfamily member 19 (Tnfrsf19) in ceRNA networks. These results showed that the expression profiles of lncRNAs and mRNAs in the liver changed after C. sinensis infection. Our results provided valuable insights into the lncRNAs and mRNAs involved in clonorchiasis pathogenesis, which may be useful for future control strategies.

Abstract As a highly endangered species, the giant panda (panda) has attracted significant attention in the past decades. Considerable efforts have been put on panda conservation and reproduction, offering the promising outcome of maintaining the population size of pandas. To evaluate the effectiveness of conservation and management strategies, recognizing individual pandas is critical. However, it remains a challenging task because the existing methods, such as traditional tracking method, discrimination method based on footprint identification, and molecular biology method, are invasive, inaccurate, expensive, or challenging to perform. The advances of imaging technologies have led to the wide applications of digital images and videos in panda conservation and management, which makes it possible for individual panda recognition in a noninvasive manner by using image‐based panda face recognition method. In recent years, deep learning has achieved great success in the field of computer vision and pattern recognition. For panda face recognition, a fully automatic deep learning algorithm which consists of a sequence of deep neural networks (DNNs) used for panda face detection, segmentation, alignment, and identity prediction is developed in this study. To develop and evaluate the algorithm, the largest panda image dataset containing 6,441 images from 218 different pandas, which is 39.78% of captive pandas in the world, is established. The algorithm achieved 96.27% accuracy in panda recognition and 100% accuracy in detection. This study shows that panda faces can be used for panda recognition. It enables the use of the cameras installed in their habitat for monitoring their population and behavior. This noninvasive approach is much more cost‐effective than the approaches used in the previous panda surveys.

Abstract Background The participation of long noncoding RNAs (lncRNAs) in myocardial infarction has recently been noted. However, their underlying roles in the border zone of myocardial infarction remain unclear. This study uses microarrays to determine the profiles of lncRNAs and mRNAs in the border zone. Methods Bioinformatics methods were employed to uncover their underlying roles. Highly dysregulated lncRNAs was further validated via PCR. Results Four hundred seven lncRNAs and 752 mRNAs were upregulated, while 132 lncRNAs and 547 mRNAs were downregulated in the border zone of myocardial infarction. A circos graph was constructed to visualize the chromosomal distribution and classification of the dysregulated lncRNAs and mRNAs. The upregulated mRNAs in the border zone were most highly enriched in cytokine activity, binding, cytokine receptor binding and related processes, as ascertained through Go analysis. Pathway analysis of the upregulated mRNAs showed the most significant changes were in the TNF signaling pathway, cytokine–cytokine receptor interaction and chemokine signaling pathway and similar pathways and interactions. An lncRNA–mRNA co-expression network was established to probe into the underlying functions of the 10 most highly dysregulated lncRNAs based on their co-expressed mRNAs. In the co-expression network, we found 16 genes directly involved in myocardial infarction, including Alox5ap, Itgb2 and B4galt1. The lncRNAs AY212271, EF424788 and MRAK088538, among others, might be associated with myocardial infarction. BC166504 is probably a key lncRNA in the border zone of myocardial infarction. Conclusions The results may have revealed some aberrantly expressed lncRNAs and mRNAs that contribute to the underlying pathophysiological mechanisms of myocardial infarction.

It is necessary for TPL firms to understand the source of power and the relationship between buyers and suppliers so that they can improve logistics performance and customer satisfaction. This paper uses a meta-analysis to assess the effect of power on the relationships and customer satisfaction in a logistics triadic relationship. A meta-analysis is useful to systemically synthesize the research findings from the existing literature. The causal relationships between power, relationship and customer satisfaction from the SCM and logistics literature are statistically assessed. Based on the review and analysis, the framework may provide significant implications for supply chain relationships in logistics. This may be the first attempt to analyse the impact of power on the relationship and customer satisfaction in a logistics triad through a meta-analysis. The results of this study will provide useful research information that other researchers can use. Keywords: Logistics triad, Power, Relationship, Logistics service performance, Meta-analysis

As one of the most important examinations in China, the National College Entrance Examination (commonly known as the Gaokao, hereafter denoted Gaokao) has a long history and has attracted attention from the Chinese educational community, among others. This study focused on mathematics test items of the Gaokao from the perspective of mathematical culture and examined the national papers (drafted by the Ministry of Education of the People’s Republic of China) of tests from 1978 to 2021 in order to investigate the content and time variation characteristics of mathematics test items reflecting mathematical culture since its restoration. A mathematical culture categorization conceptual framework was established based on previous studies and was applied to test item analysis. Mathematical culture in test items was classified using four categories: Historical Topics, Interdisciplinary Connections, Social Roles, and Aesthetics & Recreation. These were used for data coding and analysis. The results showed that mathematical culture in the mathematics test items of the Gaokao over a 44-year period, in terms of content categories, was diverse but uneven in distribution, with greater focus on demonstrating the social roles of mathematics and less on the historical development of mathematical knowledge. Moreover, the average number of items with mathematical culture during this period was small and fluctuated over time. The content of topics related to social context and technology also changed over time with the distinct characteristics of the times and changes in society. This study provides empirical evidence on how mathematical culture is integrated into test items and how they have changed over time.

Objectives: This study aimed to identify variables and develop a prediction model that could estimate extubation failure (EF) in preterm infants.Study Design: We enrolled 128 neonates as a training cohort and 58 neonates as a validation cohort. They were born between 2015 and 2020, had a gestational age between 250/7 and 296/7 weeks, and had been treated with mechanical ventilation through endotracheal intubation (MVEI) because of acute respiratory distress syndrome. In the training cohort, we performed univariate logistic regression analysis along with stepwise discriminant analysis to identify EF predictors. A monogram based on five predictors was built. The concordance index and calibration plot were used to assess the efficiency of the nomogram in the training and validation cohorts.Results: The results of this study identified a 5-min Apgar score, early-onset sepsis, hemoglobin before extubation, pH before extubation, and caffeine administration as independent risk factors that could be combined for accurate prediction of EF. The EF nomogram was created using these five predictors. The area under the receiver operator characteristic curve was 0.824 (95% confidence interval 0.748–0.900). The concordance index in the training and validation cohorts was 0.824 and 0.797, respectively. The calibration plots showed high coherence between the predicted probability of EF and actual observation.Conclusions: This EF nomogram was a useful model for the precise prediction of EF risk in preterm infants who were between 250/7 and 296/7 weeks' gestational age and treated with MVEI because of acute respiratory distress syndrome.

Aim: The present study was established to investigate the use of the serum cystatin C/prealbumin (Cys-C/PAB) ratio as a predictive factor for long-term prognosis in patients with chronic heart failure.Methods: We divided our retrospective cohort of 6,311 patients admitted to hospital due to an episode of heart failure (HF) into three groups according to the Cys-C/PAB ratio. The endpoints were cardiovascular and all-cause mortality. Median follow-up time were 3.3 years (2–8 years), during which 2,945 (46.7%) patients died.Results: The Cys-C/PAB ratio was revealed to be an independent predictor of cardiovascular mortality (HR: 1.12, 95% CI: 1.15–1.23, P < 0.01) and all-cause mortality (HR: 1.19, 95% CI: 1.13–1.24, P < 0.01) by multivariable Cox analysis. Integrated discrimination improvement (IDI) showed that the Cys-C/PAB ratio in conjunction with the level of N-terminal pro-B-type natriuretic peptide (NT-proBNP) conferred a significant improvement in predicting individual risks of cardiovascular (P = 0.023) and all-cause (P = 0.028) mortality. For those with a high Cys-C/PAB ratio in combination with a high NT-proBNP level, the long-term cardiovascular mortality risk ratio was 8.6-times higher than for those with low values, and 7.51-times for all-cause mortality. Our study also showed that Cys-C/PAB and NT-proBNP in combination displayed higher value for the prediction of cardiovascular and all-cause in-hospital mortality in patients with HF.Conclusions: The Cys-C/PAB ratio is valuable for predicting cardiovascular and all-cause mortality in patients with HF and offers additional information to that provided by NT-proBNP.

κ-Carrageenan hexamer (KCH, α-DA-1 → 3-β-G4S-1 → 4-α-DA-1 → 3-β-G4S-1 → 4-α-DA-1 → 3-G4Srα/β) are negatively charged sulfated oligosaccharides that demonstrate broad-spectrum immunoregulatory activities. However, the functional mechanism and interaction sites of KCH with recognition proteins have not been elucidated. The study aimed to investigate the anti-inflammatory signaling pathways and expound the mechanism of KCH competing with LPS in LPS-induced RAW264.7 macrophages. Expression of cytokines (NO, TNF-α, IL-β, IL-8), genes (mTNF-α, mIL-β, mIL-8) and proteins (iNOS, COX-2) involved in inflammation were significantly suppressed (p

Clonorchiasis is an important zoonotic parasitic disease worldwide. In view of the fact that parasite infection affects host metabolism, and there is an intricate relationship between metabolism and immunity. Metabolic analysis of the spleen could be helpful for understanding the pathophysiological mechanisms in clonorchiasis. A non-targeted ultra high performance liquid tandem chromatography quadrupole time of flight mass spectrometry (UHPLC-QTOF MS) approach was employed to investigate the metabolic profiles of spleen in rats at 4 and 8 weeks post infection with Clonorchis sinensis (C. sinensis). Then a targeted ultra-high performance liquid chromatography multiple reaction monitoring mass spectrometry (UHPLC-MRM-MS/MS) approach was used to further quantify amino acid metabolism. Multivariate data analysis methods, such as principal components analysis and orthogonal partial least squares discriminant analysis, were used to identify differential metabolites. Finally, a total of 396 and 242 significant differential metabolites were identified in ESI+ and ESI− modes, respectively. These metabolites included amino acids, nucleotides, carboxylic acids, lipids and carbohydrates. There were 38 significantly different metabolites shared in the two infected groups compared with the control group through the Venn diagram. The metabolic pathways analysis revealed that pyrimidine metabolism, aminoacyl-tRNA biosynthesis, purine metabolism and phenylalanine, tyrosine and tryptophan biosynthesis were significantly enriched in differential metabolites, which was speculated to be related to the disease progression of clonorchiasis. Furthermore, 15 amino acids screened using untargeted profiling can be accurately quantified and identifed by targeted metabolomics during clonrochiasis. These results preliminarily revealed the perturbations of spleen metabolism in clonorchiasis. Meanwhile, this present study supplied new insights into the molecular mechanisms of host-parasite interactions.

Major histocompatibility complex (MHC) class II deficiency is a rare and fatal primary combined immunodeficiency. It affects both marrow-derived cells and thymic epithelium, leading to impaired antigen presentation by antigen presenting cells and delayed and incomplete maturation of CD4+ lymphocyte populations. Affected children are susceptible to multiple infections by viruses, Pneumocystis jirovecii, bacteria and fungi. Immunological assessment usually shows severe CD4+ T-lymphocytopenia, hypogammaglobulinemia, and lack of antigen-specific antibody responses. The diagnosis is confirmed by absence of constitutive and inducible expression of MHC class II molecules on affected cell types which is the immunologic hallmark of the disease. Hematopoietic cell transplantation (HCT) is the only established curative therapy for MHC class II deficiency but it is difficult as affected children have significant comorbidities at the time of HCT. Optimization organ function, implementing a reduced toxicity conditioning regimen, improved T-cell depletion techniques using serotherapy and graft manipulation, vigilant infection surveillance, pre-emptive and aggressive therapy for infection and newer treatments for graft-versus-host disease have improved the transplant survival for children with MHC class II deficiency. Despite persistent low CD4+ T-lymphopenia reported in post-HCT patients, transplanted patients show normalization of antigen-specific T-lymphocyte stimulation and antibody production in response to immunization antigens. There is a need for a multi-center collaborative study to look at transplant survival of HCT and long-term disease outcome in children with MHC class II deficiency in the modern era of HCT.

Lithium-based rechargeable batteries suffer from unstable evolution of solid-electrolyte interphase on the electrode surface. Here, the authors provide an approach to inhibiting SEI formation by controlling electric potential distribution across electrolyte and electrode.

Abstract Background Hepatic iron overload has been implicated in many liver diseases; however, whether it is involved in clonorchiasis remains unknown. The purpose of this study is to investigate whether Clonorchis sinensis (C. sinensis) infection causes hepatic iron overload, analyze the relationship between the iron overload and associated cell apoptosis, so as to determine the role of excess iron plays in C. sinensis-induced liver injury. Methods The Perls’ Prussian staining and atomic absorption spectrometry methods were used to investigate the iron overload in hepatic sections of wistar rats and patients infected with C. sinensis. The hepatic apoptosis was detected by transferase uridyl nick end labeling (TUNEL) methods. Spearman analysis was used for determining the correlation of the histological hepatic iron index and the apoptotic index. Results Blue iron particles were deposited mainly in the hepatocytes, Kupffer cells and endothelial cells, around the liver portal and central vein area of both patients and rats. The total iron score was found to be higher in the infected groups than the respective control from 8 weeks. The hepatic iron concentration was also significantly higher in treatment groups than in control rats from 8 weeks. The hepatocyte apoptosis was found to be significantly higher in the portal area of the liver tissue and around the central vein. However, spearman’s rank correlation coefficient revealed that there was a mildly negative correlation between the iron index and hepatocyte apoptosis. Conclusions This present study confirmed that hepatic iron overload was found during C. sinensis infection. This suggests that iron overload may be associated with hepatocyte apoptosis and involved in liver injury during C. sinensis infection. Further studies are needed to investigate the molecular mechanism involved here.

Purpose: Pediatric medulloblastoma (MB) treatment has evolved over the past few decades; however, treating children in countries with limited resources remains challenging. Until now, the literature regarding childhood MB in Malaysia has been nonexistent. Our objectives were to review the demographics and outcome of pediatric MB treated at the University Malaya Medical Center between January 1994 and December 2013 and describe the challenges encountered. Methods: Fifty-one patients with childhood MB were seen at University Malaya Medical Center. Data from 43 patients were analyzed; eight patients were excluded because their families refused treatment after surgery. Results: Headache and vomiting were the most common presenting symptoms, and the mean interval between symptom onset and diagnosis was 4 weeks. Fourteen patients presented with metastatic disease. Five-year progression-free survival (± SE) for patients ≥ 3 years old was 41.7% ± 14.2% (95% CI, 21.3% to 81.4%) in the high-risk group and 68.6% ± 18.6% (95% CI, 40.3% to 100%) in the average-risk group, and 5-year overall survival (± SE) in these two groups was 41.7% ± 14.2% (95% CI, 21.3% to 81.4%) and 58.3% ± 18.6% (95% CI, 31.3% to 100%), respectively. Children younger than 3 years old had 5-year progression-free and overall survival rates (± SE) of 47.6% ± 12.1% (95% CI, 28.9% to 78.4%) and 45.6% ± 11.7% (95% CI, 27.6% to 75.5%), respectively. Time to relapse ranged from 4 to 132 months. Most patients who experienced relapse died within 1 year. Febrile neutropenia, hearing loss, and endocrinopathy were the most common treatment-related complications. Conclusion: The survival rate of childhood MB in Malaysia is inferior to that usually reported in the literature. We postulate that the following factors contribute to this difference: lack of a multidisciplinary neuro-oncology team, limited health care facilities, inconsistent risk assessment, insufficient data in the National Cancer Registry and pathology reports, inadequate long-term follow-up, and cultural beliefs leading to treatment abandonment.

This paper proposes an ontology-based noise source identification method, establishes an ontology knowledge expression model in the field of noise, vibration, and harshness (NVH), and provides an extensible framework for sharing noise diagnosis knowledge in the field. Based on the key features extracted from the noise and vibration signals at different positions and the prior knowledge, mechanical engineers can construct an ontology rule and locate noise sources by identifying the intrinsic relationship between signal characteristics through ontology reasoning. A case study is conducted to demonstrate the effectiveness of the proposed method in resolving the problem of integrating multisource heterogeneous knowledge and exchanging noise diagnosis knowledge information in the field of NVH for agricultural machines. Thus, our study facilitates the sharing and reuse of knowledge and advances the development of intelligent noise diagnosis expert systems to a certain extent.

Studying the genetic diversity of parasite is important for understanding their biogeography and molecular epidemiology, as well as for establishing disease prevention and control strategies. Clonorchis sinensis is an important foodborne parasite worldwide. However, despite its epidemiological significance, the genetic diversity of C. sinensis has not been well studied from human in northeastern China. In this study, a total of 342 fecal specimens were collected from residents living in five villages in Heilongjiang Province and analyzed for the presence of C. sinensis by PCR amplification and sequencing of the internal transcribed spacer 1 (ITS1) and ITS2 regions of nuclear ribosomal DNA. 21.64% (74/342) of fecal samples were found to be positive for C. sinensis by PCR. The sequences of the ITS1 region in 34 of the 74 samples (45.95%) matched that of MK179278, Genetic polymorphisms were observed at six nucleotide sites. The ITS2 gene sequence of 37 of the 74 samples (50%) matched that of MK179281. In conclusion, a low degree of genetic diversity between C. sinensis isolates from China and different geographical regions was found at ITS loci. Despite this conservation, sequencing of the rDNA region has provided important data that will be useful for future studies addressing the molecular evolution, biology, medical implications and ecology of C. sinensis.

This study aims to compare and analyze differences and similarities between some Korean and international logistics-related journals. To this end, this study reviewed academic journal articles published between 2007 and 2011 in three international journals. A total of 990 articles were reviewed and categorized in terms of research topics, research methods, and analytical techniques, and subsequently compared. This study is, to the authors’ knowledge, the first attempt to evaluate and compare prestigious international journals and Korean journals in the logistics-related research field similar to studies undertaken in scientific journals. The differences and similarities revealed in this study will help logistics researchers understand the interaction and communication between international and Korean journals, and how they can be used to develop logistics research at both the international and local levels.

Skeletal muscle possesses plasticity and adaptability to external and internal physiological changes. Due to these characteristics, skeletal muscle shows dramatic changes depending on its response to stimuli such as physical activity, nutritional changes, disease status, and environmental changes. Modulation of the rate of protein synthesis/degradation plays an important role in atrophic responses. The purpose of this review is to describe different features of skeletal muscle adaptation with various models of deceased use. In this review, four models were addressed: immobilization, spinal cord transection, hindlimb unloading, and aging. Immobilization is a form of decreased use in which skeletal muscle shows electrical activity, tension development, and motion. These results differ by muscle group. Spinal cord transection was selected to simulate spinal cord injury. Similar to the immobilization model, dramatic atrophy occurs in addition to fiber type conversion in this model. Despite the fact that electromyography shows unremarkable changes in muscle after hindlimb unloading, decreased muscle mass and contractile force are observed. Lastly, aging significantly decreases the numbers of muscle fibers and motor units. Skeletal muscle responses to decreased use include decreased strength, decreased fiber numbers, and fiber type transformation. These four models demonstrated different changes in the skeletal muscle. This review elucidates the different skeletal muscle adaptations in these four decreased use animal models and encourages further studies.