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Argininyl-fructosyl-glucose (AFG), a distinctive non-saponin compound isolated from red ginseng (Panax ginseng. C.A. Meyer), demonstrates neuroprotective effects. However, the molecular mechanism underlying AFG's anti-aging properties remains unclear. This study established an in vitro D-galactose-induced N2a cells subacute aging model to investigate AFG's anti-aging activity and potential mechanisms. Results indicated that AFG treatment (8 μM) significantly reduces the overexpression of aging-related proteins (p53/p21/p16) induced by D-galactose, highlighting its anti-aging efficacy. AFG concurrently diminishes ROS accumulation, lowering extracellular lactate dehydrogenase and alleviating intracellular oxidative stress. Notably, AFG suppresses the PERK/CHOP/caspase 12 pathway, reducing intracellular Ca2+ concentration and mitigating endoplasmic reticulum (ER) stress. Additionally, AFG decreases Bax and caspase 3 expression, elevates Bcl-2 and mitochondrial membrane potential, mitigating apoptosis. NAC with 4-PBA validated the results. Overall, AFG protects N2a cells from aging by reducing ER stress and apoptosis, suggesting its potential as a key substance for treating aging and neurodegenerative diseases.

Chromatin accessibility plays a vital role in gene transcriptional regulation. However, the regulatory mechanism of chromatin accessibility, as well as its role in regulating crucial gene expression and kernel development in maize (Zea mays) are poorly understood. In this study, we isolated a maize kernel mutant designated as defective kernel219 (dek219), which displays opaque endosperm and embryo abortion. Dek219 encodes the DICER-LIKE1 (DCL1) protein, an essential enzyme in miRNA biogenesis. Loss of function of Dek219 results in significant reductions in the expression levels of most miRNAs and histone genes. Further research showed that the Heat shock transcription factor17 (Hsf17)-Zm00001d016571 module may be one of the factors affecting the expression of histone genes. Assay results for transposase-accessible chromatin sequencing (ATAC-seq) indicated that the chromatin accessibility of dek219 is altered compared with that of wild type (WT), which may regulate the expression of crucial genes in kernel development. By analyzing differentially expressed genes (DEGs) and differentially accessible chromatin regions (ACRs) between WT and dek219, we identified 119 candidate genes that are regulated by chromatin accessibility, including some reported to be crucial genes for kernel development. Taken together, these results suggest that Dek219 affects chromatin accessibility and the expression of crucial genes that are required for maize kernel development.

The decrease in eggshell quality seriously affects production efficiency. Guinea fowl (GF) eggs possess strong eggshells because of their unique crystal structure, and few systematic studies have compared laying hen and GF eggs. Sixty eggs were collected from both 40-week-old Dwarf Layer-White (DWL-White) laying hens and GF, and the eggshell quality, ultrastructure, bubble pores, and composition were measured. The results showed that the DWL-White eggs had a higher egg weight and a lower eggshell strength, strength per unit weight, thickness, and ratio than the GF eggs (p < 0.01). There were differences in the mammillary layer thickness ratio, the effective layer thickness ratio, the quantity of bubble pores (QBPs), the ratio of the sum of the area of bubble pores to the area of the eggshell in each image (ARBE), and the average area of bubble pores (AABPs) between the DWL-White and GF eggs (p < 0.01). The composition analysis demonstrated that there were differences in the organic matter, inorganic matter, calcium, and phosphorus between the DWL-White and GF eggs (p < 0.01). There were positive associations between the mammillary knob number in the image and the QBPs and ARBE and a negative correlation with the AABPs in the DWL-White eggs (p < 0.01). This study observed distinctions that offer new insights into enhancing eggshell quality.

We present JefiAtten, a novel neural network model employing the attention mechanism to solve Maxwell’s equations efficiently. JefiAtten uses self-attention and cross-attention modules to understand the interplay between charge density, current density, and electromagnetic fields. Our results indicate that JefiAtten can generalize well to a range of scenarios, maintaining accuracy across various spatial distribution and handling amplitude variations. The model showcases an improvement in computation speed after training, compared to traditional integral methods. The adaptability of the model suggests potential for broader applications in computational physics, with further refinements to enhance its predictive capabilities and computational efficiency. Our work is a testament to the efficacy of integrating attention mechanisms with numerical simulations, marking a step forward in the quest for data-driven solutions to physical phenomena.

This paper is aimed to find out the impact of the geometrical parameters, mainly the radius and the height of a cylinder, on the SGEMP response including the famous scaling law in the classical cylinder model using a homemade PIC code UNIPIC-3D. We computed the electric fields at the center and at the edge on the emission head face with different radii and heights under normal X-rays incidence. The results show that the electric field will increase with the radius but decrease with the height. We analyze the scaling law that links the electric field product and fluence product, and whereafter an irreconcilable contradiction raises when the radius is changeable, which limits the application range of the scaling law. Moreover, the field-height-radius relation is found and described by a combination of logarithmic and minus one-quarter numerical fitting law firstly. Particle and magnetic field distributions are used to explain all the behaviors of the fields reasonably. All the findings will assist the evaluation of SGEMP response in spacecraft protection.

Cisplatin is the most widely used anticancer chemotherapy drug at present. However, its severe nephrotoxic side effects limit the clinical application. This study aimed to investigate the potential protective mechanism of arabinogalactan (AG) on acute kidney injury (AKI) induced by cisplatin in mice. Firstly, 105 potential targets of AG were predicted by using the SwissTargetPrediction database, 25,183 kidney disease targets were obtained by searching 5 disease databases, and 100 cross-target targets were obtained by drawing a Venn diagram. We constructed the “AG-Key target” interaction network and PPI protein interaction network of cross-targets and screened out 21 core targets. Through the GO and KEGG enrichment analysis of the core targets, we can found that the core targets involved a total of 1254 biological functions and 56 signaling pathways, including the apoptosis signaling pathway. By establishing an animal model in vivo, we found that pretreatment with AG at doses of 200 and 400 mg/kg could decrease the kidney index, such as serum creatinine (CRE), and blood urea nitrogen (BUN) levels induced by cisplatin, and reduce the kidney histopathology injury. Importantly, AG could inhibit the formation of metaldehyde (MDA) and 4-hydroxynonenal (4-HNE) in the kidney tissues and reduce the oxidative stress injury induced by cisplatin. Meanwhile, AG also restored the expression of anti-apoptotic proteins Bcl-2 and Bcl-xL and decreased the expression of pro-apoptotic proteins Bax and Bad in cisplatin-induced renal tissues. Finally, AG could further reduce cisplatin-induced kidney cell apoptosis.

IntroductionNon-alcoholic steatohepatitis (NASH), an advanced subtype of non-alcoholic fatty liver disease (NAFLD), has becoming the most important aetiology for end-stage liver disease, such as cirrhosis and hepatocellular carcinoma. This study were designed to explore novel genes associated with NASH.MethodsHere, five independent Gene Expression Omnibus (GEO) datasets were combined into a single cohort and analyzed using network biology approaches.Results11 modules identified by weighted gene co-expression network analysis (WGCNA) showed significant association with the status of NASH. Further characterization of four gene modules of interest demonstrated that molecular pathology of NASH involves the upregulation of hub genes related to immune response, cholesterol and lipid metabolic process, extracellular matrix organization, and the downregulation of hub genes related to cellular amino acid catabolic, respectively. After DEGs enrichment analysis and module preservation analysis, the Turquoise module associated with immune response displayed a remarkably correlation with NASH status. Hub genes with high degree of connectivity in the module, including CD53, LCP1, LAPTM5, NCKAP1L, C3AR1, PLEK, FCER1G, HLA-DRA and SRGN were further verified in clinical samples and mouse model of NASH. Moreover, single-cell RNA-seq analysis showed that those key genes were expressed by distinct immune cells such as microphages, natural killer, dendritic, T and B cells. Finally, the potential transcription factors of Turquoise module were characterized, including NFKB1, STAT3, RFX5, ILF3, ELF1, SPI1, ETS1 and CEBPA, the expression of which increased with NASH progression.DiscussionIn conclusion, our integrative analysis will contribute to the understanding of NASH and may enable the development of potential biomarkers for NASH therapy.

AIM:To evaluate the safety and efficacy of 0.005% atropine eye drops on myopia control in children with low myopia. METHODS: Prospective one-year controlled study. One hundred and sixteen children with low myopia were divided into two groups(0.005% atropine group and control group)according to the requirements of children and their guardians. The children(n=58)in the 0.005% atropine group wore single-vision(SV)spectacles, with one drop of 0.005% atropine eye drop applied to both eyes once nightly. The children(n=58)in the control group only wore SV spectacles. Repeated measurements of spherical equivalent refractive errors(SERs), axial length(AL), pupil diameter and accommodative amplitude were performed at baseline, and 4, 8 and 12mo after treatment. The discomfort symptoms were also observed.RESULTS: There were no significant increase shown in change in SERs and AL from baseline to 12mo in the 0.005% atropine group and control group(P0.05). Statistically significant differences were all found in pupil diameter increase and accommodative amplitude decrease between two groups( P

Graphic Processing Units (GPUs) are becoming popular in computational physics. Seeing the increasing trend of using GPUs in the physics community, we provide a comparison of the two major packages Numba and CuPy for GPU coding in Python language. We have discussed the influence of the data amount and data type on the performance of the GPU code. The data transferring time from GPU to CPU and its influence on the total execution time has also been analyzed. We find that when the grid numbers reaches 107, Numba will be faster than CuPy. Meanwhile, there is no noticeable difference in the data transmission speed between Numba and CuPy. Setting the data types as single-precision in Numba programs can improve the computation time by at least 20%.

The current study aimed to reveal the inhibitory effect of Platycodin D (PD) on intestinal cell apoptosis mediated by ER stress. Treatment with PD alleviated pathological changes of the intestine and reduced secretion of intracellular enzyme Diamine oxidase (DAO) in the upper villi of the small intestinal mucosa in Cisplatin (CP) intestinal injury model and increased expression of key protein Occludin and ZO-1 of the intestinal mechanical barrier. PD inhibited ER stress in a dose-dependent in CP-caused IEC-6 cells and the level of phosphorylation of Protein kinase R-like ERK kinase (PERK) and Eukaryotic initiation factor-2 alpha (eIF2α) reduced. Besides, the ER stress inhibitor 4-PBA was used to confirm that PD alleviated the ER stress in vitro. In conclusion, PD exerted an intestinal protective effect through the inhibition of ER stress in CP-treated mice and IEC-6 cells. These data indicated that PD was a promising natural medicine for intestinal protection.

Postfinasteride syndrome (PFS) is a term coined to characterize a constellation of reported undesirable sexual, physical, and neuropsychiatric side effects. In the present study, we conducted the meta-analysis to demonstrate whether the use of 5α-reductase inhibitors (5ARIs) increases the risk of PFS-like adverse effects. A search of studies published until May 10, 2020, was performed using PubMed, EMBASE, and the Cochrane Library. We included randomized controlled trials with at least one comparison between male patients receiving 5ARIs versus placebo for the treatment of benign prostatic hyperplasia (BPH) or androgenetic alopecia (AGA), and identified 34 studies from 28 articles that met our eligibility criteria. In the random-effects model, the overall use of 5ARIs exhibited a 1.87-fold risk of PFS-like adverse effects during the trial (95% confidence interval [CI]: 1.64–2.14). Regarding specific types of adverse effects, the use of 5ARIs had a 1.89-fold risk of sexual adverse effects (95% CI: 1.74–2.05) and was associated with an increased risk of physical adverse effects (relative risk [RR]: 1.31, 95% CI: 0.80–2.15), albeit without statistical significance. This meta-analysis helped to better define the adverse effects caused by 5ARIs. We concluded that the overall use of 5ARIs significantly increased the risk of PFS-like adverse effects in men with AGA or BPH during treatment. Enhanced awareness of and education on the PFS-like adverse effects are necessary for clinicians.

In this work, a dual-band transmissive polarization conversion metasurface (PCM), with omnidirectional polarization and low profile, is proposed. The periodic unit of the PCM is composed of three metal layers separated by two substrates. The upper patch layer of the metasurface is the patch-receiving antenna, while the bottom layer is the patch-transmitting antenna. Both antennas are arranged in an orthogonal way so that the cross-polarization conversion can be realized. The equivalent circuit analysis, structure design, and experimental demonstration are conducted in detail, the polarization conversion rate (PCR) is greater than 90% within two frequency bands of 4.58–4.69 GHz and 5.33–5.41 GHz, and the PCR at two center operating frequencies of 4.64 GHz and 5.37 GHz is as high as 95%, with a thickness of only 0.062λL, where λL is the free space wavelength at the lowest operating frequency. The PCM can realize a cross-polarization conversion, when the incident linearly polarized wave at an arbitrary polarization azimuth, which indicates that it has the characteristics of omnidirectional polarization.

BackgroundProvisional stenting (PS) is the main treatment for a majority of coronary bifurcation lesion and includes PS with 1-stent and PS with 2-stent. However, the treatment difference between PS with 1-stent and with 2-stent remains unclear in patients with the acute coronary syndrome (ACS) and coronary bifurcation lesions.Materials and methodsOverall, 820 ACS patients with Medina 1,1,1 or 0,1,1 coronary bifurcation lesion who had completed 3-year follow-up were included and assigned to the PS with 1-stent (n = 519) or the PS with 2-stent (n = 301) according to the use of final stenting technique. The primary endpoint was the target lesion failure (TLF) at 3 years since stenting procedures.ResultsAt 3-year follow-up, TLF occurred in 85 (16.4%) patients in the PS with 1-stent group and 69 (22.9%) in the PS with 2-stent group (hazard ratio [HR] 1.52, 95% confidence interval [CI] 1.06–2.17, p = 0.021), mainly driven by a higher rate of target lesion revascularization (TLR) in the PS with 2-stent group (13.0% vs. 8.3%, HR 1.65, 95% CI 1.04–2.61, p = 0.033). Complex bifurcations, side branch (SB) pretreatment, intravascular imaging guidance, and hyperlipidemia were the four predictors for 3-year TLF. SB pretreatment was associated with increased 3-year TLR, leading to an extremely higher 3-year TLF.ConclusionProvisional with 2-stent for patients with ACS is associated with a higher rate of 3-year TLF, mainly due to increased requirement of revascularization. SB pretreatment should be avoided for simple bifurcation lesion.

The present study investigated the protective effects of crude saponins (ginsenosides) in berries in an brain injury model by intraperitoneal injection of D-gal (D-galactose). Our study showed that ginseng berry saponin (GBS) treatment significantly improved memory impairment in mice. Meanwhile, long-term exposure to D-gal reduces the expression of cholinergic modulators such as choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), which can be significantly improved after administration. Furthermore, we found that GBS improved redox levels in the brain. In addition, TUNEL staining results showed that GBS inhibited D-Gal-induced apoptosis. Finally, we found that GBS treatment delayed cell aging by modulating the expression levels of cyclin D1 and senescence proteins p16 and p21, and further attenuated oxidative stress by activating SIRT1/Akt pathway. These results suggest that GBS can effectively treat D-Gal-induced brain damage and may be a potential therapeutic agent for slowing down the aging process.

Background Despite the clinical benefits to intravascular ultrasound (IVUS) guidance for percutaneous coronary intervention (PCI), most patients with coronary artery disease undergo angiography‐guided PCI alone in the real‐world setting. We sought to investigate the procedural characteristics of IVUS‐guided PCI and their clinical outcomes, as compared with angiography‐guided PCI. Methods and Results This was a cohort study using patient‐level data from the IVUS‐XPL (Impact of Intravascular Ultrasound Guidance on the Outcomes of Xience Prime Stents in Long Lesions) and ULTIMATE (Intravascular Ultrasound Guided Drug Eluting Stents Implantation in All‐Comers Coronary Lesions) clinical trials. A total of 2848 patients with 3872 native coronary lesions were included and procedural characteristics assessed by quantitative coronary angiography (QCA) were compared between IVUS and angiography guidance. Stent‐to‐reference vessel diameter ratio (ie, QCA stent sizing) was greater (1.11±0.16 versus 1.07±0.14, P

Although the antagonistic effects of saponins (Ginsenosides) from ginseng on the side effects caused by cisplatin have been widely confirmed, there are few reports on the non-saponins of small molecules. Maltol, as an important active ingredient and a naturally occurring flavor enhancer produced in the process of red ginseng, has been proven to have good pharmacological activity. The purpose of this study is to explore the protective effect and possible mechanisms of maltol on cisplatin-induced intestinal toxicity in vivo and in vitro. A single injection of cisplatin (20 mg/kg) caused significant damage to the intestinal function of mice, shrinkage of the small intestine, and sharply increased the diamine oxidase (DAO) index of intestinal function, which exacerbates the occurrence of oxidative stress damage. After administration of maltol (50 and 100 mg/kg), these symptoms were remarkably relieved. Notably, in cultured IEC-6 cells, maltol treatment improved the occurrence of oxidative stress during cisplatin exposure, significantly inhibited the excessive release of ROS, and attenuated the cisplatin-induced increase in NLRP3 inflammasome release. The findings indicating that maltol inhibits oxidative stress and pyroptosis, and further reduces cisplatin-induced apoptosis. In conclusion, the results of this study indicated that maltol exerts the protective effects of cisplatin-induced intestinal toxicity by reducing the release of ROS and inhibiting the activation of apoptosis.

Vascular smooth muscle cells (VSMCs), the major cell type in the arterial vessel wall, have a contractile phenotype that maintains the normal vessel structure and function under physiological conditions. In response to stress or vascular injury, contractile VSMCs can switch to a less differentiated state (synthetic phenotype) to acquire the proliferative, migratory, and synthetic capabilities for tissue reparation. Imbalances in VSMCs phenotypic switching can result in a variety of cardiovascular diseases, including atherosclerosis, in-stent restenosis, aortic aneurysms, and vascular calcification. It is very important to identify the molecular mechanisms regulating VSMCs phenotypic switching to prevent and treat cardiovascular diseases with high morbidity and mortality. However, the key molecular mechanisms and signaling pathways participating in VSMCs phenotypic switching have still not been fully elucidated despite long-term efforts by cardiovascular researchers. In this review, we provide an updated summary of the recent studies and systematic knowledge of VSMCs phenotypic switching in atherosclerosis, in-stent restenosis, aortic aneurysms, and vascular calcification, which may help guide future research and provide novel insights into the prevention and treatment of related diseases.

Objectives: We investigated the influence of coronary disease characteristics on prognostic implications of residual ischemia after coronary stent implantation.Methods: This study included 1,476 patients with drug-eluting stent implantation and available pre- and post-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) measurements. Residual ischemia was defined as post-PCI FFR ≤ 0.80. Coronary disease characteristics with significant interaction hazard ratios (HRs) for clinical outcomes with residual ischemia were defined as interaction characteristics with residual ischemia (ICwRI). The primary outcome was target vessel failure (TVF)—a composite of cardiac death, target vessel myocardial infarction, and target vessel revascularization—at 2 years.Results: The mean pre- and post-PCI FFR were 0.68 ± 0.11 and 0.87 ± 0.07, respectively. During the median follow-up duration of 2.0 years, the cumulative incidence of TVF was 6.1%. The 203 vessels (13.8%) with residual ischemia had higher risks of TVF compared to that for post-PCI FFR >0.80 (P < 0.001). ICwRI with a significant interaction HR with residual ischemia included pre-PCI SYNTAX score >17 and pre-PCI FFR ≤ 0.62. Each ICwRI had a direct prognostic effect not mediated by residual ischemia. The association between an increased TVF risk and residual ischemia was significant in patients with 0 or 1 ICwRI [hazard ratio (HR) 3.25, 95% confidence interval (CI) 1.90–5.57, P < 0.001] but not in those with 2 ICwRI (HR 0.47, 95% CI 0.14–1.64, P = 0.24). Among patients with post-PCI FFR >0.80, those with 2 ICwRI showed similar TVF risks to those with residual ischemia (HR 1.55, 95% CI 0.79–3.02, P = 0.20).Conclusions: Coronary disease characteristics including pre-PCI SYNTAX score and pre-PCI FFR affected the prognostic implications of residual ischemia. The prognostic relevance of residual ischemia was attenuated in patients with multiple interacting characteristics.

Aims: In-stent restenosis (ISR) remains an Achilles heel of drug-eluting stents despite technical advances in devices and procedural techniques. Neointimal hyperplasia (NIH) is the most important pathophysiological process of ISR. The present study mapped normal arteries and stenotic arteries to uncover potential cellular targets of neointimal hyperplasia.Methods and Results: By comparing the left (control) and right (balloon injury) carotid arteries of rats, we mapped 11 clusters in normal arteries and 11 mutual clusters in both the control and experimental groups. Different clusters were categorized into 6 cell types, including vascular smooth muscle cells (VSMCs), fibroblasts, endothelial cells (ECs), macrophages, unknown cells and others. An abnormal cell type expressing both VSMC and fibroblast markers at the same time was termed a transitional cell via pseudotime analysis. Due to the high proportion of VSMCs, we divided them into 6 clusters and analyzed their relationship with VSMC phenotype switching. Moreover, N-myristoyltransferase 1 (NMT1) was verified as a credible VSMC synthetic phenotype marker. Finally, we proposed several novel target genes by disease susceptibility gene analysis, such as Cyp7a1 and Cdk4, which should be validated in future studies.Conclusion: Maps of the heterogeneous cellular landscape in the carotid artery were defined by single-cell RNA sequencing and revealed several cell types with their internal relations in the ISR model. This study highlights the crucial role of VSMC phenotype switching in the progression of neointimal hyperplasia and provides clues regarding the underlying mechanism of NIH.

Ni-Al LDHs was electrodeposited from a NiCl2-AlCl3 solution. In order to analyze the electrodeposition process, electrolytes with initial Al content range of 0–20% were used. With increasing Al content in the sample, the preferred orientations of (0 0 3) and (0 0 6), increased crystallinity, and decreased interlayer spacing were observed from the XRD results. A dissolution–recrystallization of (0 0 3) plane was detected among the Ni-Al LDHs from the strongly alkaline solution soaking results, which was found to be conducted easily in high Al-containing samples. The pH of the Al-containing electrolyte was much lower than that of pure NiCl2 solution because lower pH was needed to start a precipitation reaction in the AlCl3-NiCl2 solution. The electrodeposition yield and current efficiency were found to decrease obviously in the electrolytes with initial Al content higher than 10%, which was attributed to the increasing Al content in the sample and diffusion of the complex ions. The electrodeposition pattern was in-situ in the electrolyte initially containing 10% Al, then, it developed toward and off in-situ in electrolytes initially containing 0–10% and 10–20% Al.

We have calculated the directed flow v_{1} and charge-dependent directed flow Δv_{1} of pions and protons in Au+Au collisions at sqrt[s_{NN}]=200 GeV by solving the coupled Boltzmann-Maxwell equations self-consistently. Our numerical results show that v_{1} for pions and protons are all negative in the positive midrapidity region and have similar behavior and magnitude. In contrast we find a quite different behavior in Δv_{1} for pions and protons. The difference lies in that Δv_{1} for protons mainly comes from pressure gradients of the medium, while the dominant contribution to Δv_{1} for pions is from electromagnetic fields. Our results indicate that the effect of the electric field will slightly exceed that of the magnetic field and lead to a small negative slope of Δv_{1} for pions.

Exosomes, with an diameter of 30~150 nm, could be released from almost all types of cells, which contain diverse effective constituent, such as RNAs, proteins, lipids, and so on. In recent years, exosomes have been verified to play an important role in mechanism, diagnosis, treatment, and prognosis of cardiovascular disease, especially coronary artery disease (CAD). Moreover, it has also been shown that exosomes derived from different cell types have various biological functions based on the cell stimulation and microenvironment. However, therapeutic exosomes are currently far away from clinical translation, despite it is full of hope. In this review, we summarize an update of the recent studies and systematic knowledge of therapeutic exosomes in atherosclerosis, myocardial infarction, and in-stent restenosis, which might provide a novel insight into the treatment of CAD and promote the potential clinical application of therapeutic exosomes.

BackgroundGlioma is one of the most common malignancies in the central nervous system and has limited effective therapeutic options. Therefore, we sought to identify a suitable target for immunotherapy.Materials and MethodsWe screened prognostic genes for glioma in the CGGA database and GSE43378 dataset using survival analysis, receiver operating characteristic (ROC) curves, independent prognostic analysis, and clinical correlation analysis. The results were intersected with immune genes from the ImmPort database through Venn diagrams to obtain likely target genes. The target genes were validated as prognostically relevant immune genes for glioma using survival, ROC curve, independent prognostic, and clinical correlation analyses in samples from the CGGA database and GSE43378 dataset, respectively. We also constructed a nomogram using statistically significant glioma prognostic factors in the CGGA samples and verified their sensitivity and specificity with ROC curves. The functions, pathways, and co-expression-related genes for the glioma target genes were assessed using PPI networks, enrichment analysis, and correlation analysis. The correlation between target gene expression and immune cell infiltration in glioma and the relationship with the survival of glioma patients were investigated using the TIMER database. Finally, target gene expression in normal brain, low-grade glioma, and high-grade glioma tissues was detected using immunohistochemical staining.ResultsWe identified TNFRSF12A as the target gene. Satisfactory results from survival, ROC curve, independent prognosis, and clinical correlation analyses in the CGGA and GSE43378 samples verified that TNFRSF12A was significantly associated with the prognosis of glioma patients. A nomogram was constructed using glioma prognostic correlates, including TNFRSF12A expression, primary-recurrent-secondary (PRS) type, grade, age, chemotherapy, IDH mutation, and 1p19q co-deletion in CGGA samples with an AUC value of 0.860, which illustrated the accuracy of the prognosis prediction. The results of the TIMER analysis validated the significant correlation of TNFRSF12A with immune cell infiltration and glioma survival. The immunohistochemical staining results verified the progressive up-regulation of TNFRSF12A expression in normal brain, low-grade glioma, and high-grade glioma tissues.ConclusionWe concluded that TNFRSF12A was a viable prognostic biomarker and a potential immunotherapeutic target for glioma.

Objective To investigate the efficacy and safety of tranexamic acid (TXA) in the reduction of bleeding and the need for transfusion in elderly intertrochanteric fracture patients. Methods A total of 100 patients with intertrochanteric fractures undergoing surgery were enrolled and randomly allocated to the TXA group in which patients (75.10 ± 8.27 years old) were treated with 1 g of TXA, or the control group (77.82 ± 6.42 years old) treated with a placebo. Surgery was performed by two senior orthopaedic surgeons from two institutions. The proximal femoral nail antirotation (PFNA) was conducted using the standard procedure. Three outcome measures, including blood loss, transfusion, and complications, were recorded. Blood loss and transfusion were investigated to assess TXA's effectiveness, while complications were investigated to assess TXA's safety. Statistical indicators for blood loss included total, intraoperative, postoperative, and hidden blood loss volumes, calculated by hemoglobin levels, hematocrit levels, and drainage volume. The number and amount of blood transfusions were recorded. Complications associated with surgery, including deep vein thrombosis, pulmonary embolism, wound hematoma, wound infection, cardiovascular and cerebrovascular accidents, and respiratory infections, were also recorded. Results All patients were followed up for 1 month after surgery. There were no significant differences in demographic and clinical characteristics between the two groups. The TXA group suffered significantly less total blood loss (563.37 ± 197.51 vs 819.25 ± 273.96 mL, 95% CI: −349.49 to −162.27, P

Abstract Ovarian cancer (OC) is the highest frequent malignant gynecologic tumor with very complicated pathogenesis. The purpose of the present academic work was to identify significant genes with poor outcome and their underlying mechanisms. Gene expression profiles of GSE36668, GSE14407 and GSE18520 were available from GEO database. There are 69 OC tissues and 26 normal tissues in the three profile datasets. Differentially expressed genes (DEGs) between OC tissues and normal ovarian (OV) tissues were picked out by GEO2R tool and Venn diagram software. Next, we made use of the Database for Annotation, Visualization and Integrated Discovery (DAVID) to analyze Kyoto Encyclopedia of Gene and Genome (KEGG) pathway and gene ontology (GO). Then protein-protein interaction (PPI) of these DEGs was visualized by Cytoscape with Search Tool for the Retrieval of Interacting Genes (STRING). There were total of 216 consistently expressed genes in the three datasets, including 110 up-regulated genes enriched in cell division, sister chromatid cohesion, mitotic nuclear division, regulation of cell cycle, protein localization to kinetochore, cell proliferation and Cell cycle, progesterone-mediated oocyte maturation and p53 signaling pathway, while 106 down-regulated genes enriched in palate development, blood coagulation, positive regulation of transcription from RNA polymerase II promoter, axonogenesis, receptor internalization, negative regulation of transcription from RNA polymerase II promoter and no significant signaling pathways. Of PPI network analyzed by Molecular Complex Detection (MCODE) plug-in, all 33 up-regulated genes were selected. Furthermore, for the analysis of overall survival among those genes, Kaplan–Meier analysis was implemented and 20 of 33 genes had a significantly worse prognosis. For validation in Gene Expression Profiling Interactive Analysis (GEPIA), 15 of 20 genes were discovered highly expressed in OC tissues compared to normal OV tissues. Furthermore, four genes (BUB1B, BUB1, TTK and CCNB1) were found to significantly enrich in the cell cycle pathway via re-analysis of DAVID. In conclusion, we have identified four significant up-regulated DEGs with poor prognosis in OC on the basis of integrated bioinformatical methods, which could be potential therapeutic targets for OC patients.

In artery tree, endothelial function correlates with the distribution of shear stress, a dragging force generated by flowing blood. In laminar shear stress areas, endothelial cells (ECs) are available to prevent atherosclerosis, however, ECs in disturbed shear stress sites are featured with proinflammation and atherogenesis. Basic studies in the shear stress field that focused on the mechanosensors of ECs have attracted the interest of researchers. Among all the known mechanosensors, the primary cilium is distinctive because it is enriched in disturbed shear stress regions and sparse in laminar shear stress areas. The primary cilium, a rod liked micro-organelle, can transmit extracellular mechanical and chemical stimuli into intracellular space. In the cardiovascular system, primary cilia are enriched in disturbed shear stress regions, where blood flow is slow and oscillatory, such as the atrium, downstream of the aortic valve, branches, bifurcations, and inner curves of the artery. However, in the atrioventricular canal and straight vessels, blood flow is laminar, and primary cilia can barely be detected. Primary cilia in the heart cavity prevent ECs from mesenchymal transition and calcification by suppressing transforming growth factor (TGF) signaling. Besides, primary cilia in the vascular endothelium protected ECs against disturbed shear stress-induced cellular damage by triggering Ca2+ influx as well as nitric oxide (NO) release. Moreover, primary cilia inhibit the process of atherosclerosis. In the current review, we discussed ciliogenesis, ciliary structure, as well as ciliary distribution, function and the coordinate signal transduction with shear stress in the cardiovascular system.

Metagenomic analysis of mosquito-borne and mosquito-specific viruses is useful to understand the viral diversity and for the surveillance of pathogens of medical and veterinary importance. Yunnan province is located at the southwest of China and has rich abundance of mosquitoes. Arbovirus surveillance is not conducted regularly in this province particularly at animal farms, which have public health as well as veterinary importance. Here, we have analyzed 10 pools of mosquitoes belonging to Culex tritaeniorhyncus, Aedes aegypti, Anopheles sinensis, and Armigeres subalbatus species, collected from different animal farms located at Yunnan province of China by using metagenomic next-generation sequencing technique. The generated viral metagenomic data reveal that the viral community matched by the reads was highly diverse and varied in abundance among animal farms, which contained more than 19 viral taxonomic families, specific to vertebrates, invertebrates, fungi, plants, protozoa, and bacteria. Additionally, a large number of viral reads were related to viruses that are non-classified. The viral reads related to animal viruses included parvoviruses, anelloviruses, circoviruses, flaviviruses, rhabdoviruses, and seadornaviruses, which might be taken by mosquitoes from viremic animal hosts during blood feeding. Notably, the presence of viral reads matched with Japanese encephalitis virus, Getah virus, and porcine parvoviruses in mosquitoes collected from different geographic sites suggested a potential circulation of these viruses in their vertebrate hosts. Overall, this study provides a comprehensive knowledge of diverse viral populations present at animal farms of Yunnan province of China, which might be a potential source of diseases for humans and domestic animals.

Coronary angiography has been considered the gold standard for the diagnosis of coronary artery disease and guidance of percutaneous coronary intervention (PCI). However, 2D-projection angiography cannot completely reflect the 3D coronary lumen. Intravascular ultrasound (IVUS) can overcome a number of limitations of coronary angiography by providing more information about the dimensions of the vessel lumen, plaque characteristics, stent deployment, and the mechanisms of device failure. Growing data from observational studies and randomized controlled trials have confirmed the clinical benefit of IVUS guidance during PCI. This article summarizes the evidence regarding IVUS guidance to highlight its advantages and to support the use of IVUS during PCI.

Abstract Background The relationship between platelet reactivity and long-term clinical outcomes remains controversial. The present prospective study was designed to explore the association between high platelet reactivity (HPR) on clopidogrel and long-term clinical outcomes following implantation of drug eluting stents (DES). Methods A total of 1769 consecutive patients assessed by Aggrestar (PL-11) were enrolled at our center from February 2011 to December 2017. The primary end point was major adverse cardiovascular and cerebrovascular events (MACCE), defined as definite or probable stent thrombosis, spontaneous myocardial infarction, all cause death, clinically driven target vessel revascularization (TVR), or ischemic stroke. Bleeding served as the safety endpoint. Propensity score matching (PSM) analysis was performed to adjust for baseline differences in the overall cohort. Results Finally, 409 patients (23.1%) were identified with HPR on clopidogrel. At a median follow-up of 4.1 years (interquartile range, 1.8 years), the occurrence of MACCE was significantly higher in HPR on clopidogrel group than normal platelet reactivity (NPR) on clopidogrel group (15.6% vs. 5.4%, p

Zenia insignis Chun is a large, fast-growing deciduous tree. In this study, we successfully developed a reliable and efficient protocol for the regeneration of fertile plants via callus induction from leaf segments of young Z. insignis seedlings. The best results were obtained with a medium containing 11.00 μM 6-benzyladenine (6-BA), 1.20 μM indole-3-butytric acid (IBA), and 0.45 μM 2,4-dichlorophenoxyacetic acid (2,4-D), which yielded morphogenic callus within 2 weeks at a frequency of 62.23%. We tested the effect of IBA alone and in combination with 6-BA on the bud differentiation response of Z. insignis callus. Shoots differentiated normally when cultured on differentiation medium containing 6.00 μM 6-BA and 1.20 μM IBA. Regenerated buds elongated successfully in medium containing 1.20 μM gibberellic acid (GA3). The elongated shoots were then transferred to Murashige and Skoog basal medium supplemented with various combinations of naphthalene acetic acid (NAA) for root induction; well-developed roots were achieved on MS basal medium supplemented with 0.01 μM NAA at a rooting rate of 89.23%. Rooted plantlets were successfully acclimatised to a greenhouse at a survival rate exceeding 90.00%.

Background: The relationship between obstructive sleep apnea (OSA) and platelet reactivity in patients undergoing percutaneous coronary intervention (PCI) has not been defined. The present prospective, single-center study explored the relationship between platelet reactivity and OSA in patients with PCI. Methods: A total of 242 patients were finally included in the study. OSA was screened overnight by polysomnography. Platelet reactivity was assessed with a sequential platelet counting method, and the platelet maximum aggregation ratio (MAR) and average aggregation ratio were calculated. All patients were assigned per apnea-hypopnea index (AHI) to non-OSA (n = 128) and OSA (n = 114) groups. The receiver operating characteristic curve analysis was used to evaluate the accuracy of AHI for high platelet reactivity (HPR) on aspirin and clopidogrel, and multivariable logistic regression was used to determine the independent predictors of HPR on aspirin and clopidogrel. Results: Median AHI was significantly higher in the OSA group than in the non-OSA group (34.5 events/h vs. 8.1 events/h, Z = −13.422, P < 0.001). Likewise, median arachidonic acid- and adenosine diphosphate-induced maximum aggregation rate (MAR) in the OSA group was significantly higher than those in the non-OSA group (21.1% vs. 17.7%, Z = −3.525, P < 0.001 and 45.8% vs. 32.2%, Z = −5.708, P < 0.001, respectively). Multivariable logistic regression showed that OSA was the only independent predictor for HPR on aspirin (odds ratio [OR]: 1.055, 95% confidence interval [CI]: 1.033–1.077, P < 0.001) and clopidogrel (OR: 1.036, 95% CI: 1.017–1.056, P < 0.001). The cutoff value of AHI for HPR on aspirin was 45.2 events/h (sensitivity 47.1% and specificity 91.3%), whereas cutoff value of AHI for HPR on clopidogrel was 21.3 events/h (sensitivity 68.3% and specificity 67.7%). Conclusion: Platelet reactivity appeared to be higher in OSA patients with PCI despite having received a loading dose of aspirin and clopidogrel, and OSA might be an independent predictor of HPR on aspirin and clopidogrel.

Leptospirosis, caused by spirochetes of the genus Leptospira, is a globally widespread, neglected and emerging zoonotic disease. While whole genome analysis of individual pathogenic, intermediately pathogenic and saprophytic Leptospira species has been reported, comprehensive cross-species genomic comparison of all known species of infectious and non-infectious Leptospira, with the goal of identifying genes related to pathogenesis and mammalian host adaptation, remains a key gap in the field. Infectious Leptospira, comprised of pathogenic and intermediately pathogenic Leptospira, evolutionarily diverged from non-infectious, saprophytic Leptospira, as demonstrated by the following computational biology analyses: 1) the definitive taxonomy and evolutionary relatedness among all known Leptospira species; 2) genomically-predicted metabolic reconstructions that indicate novel adaptation of infectious Leptospira to mammals, including sialic acid biosynthesis, pathogen-specific porphyrin metabolism and the first-time demonstration of cobalamin (B12) autotrophy as a bacterial virulence factor; 3) CRISPR/Cas systems demonstrated only to be present in pathogenic Leptospira, suggesting a potential mechanism for this clade's refractoriness to gene targeting; 4) finding Leptospira pathogen-specific specialized protein secretion systems; 5) novel virulence-related genes/gene families such as the Virulence Modifying (VM) (PF07598 paralogs) proteins and pathogen-specific adhesins; 6) discovery of novel, pathogen-specific protein modification and secretion mechanisms including unique lipoprotein signal peptide motifs, Sec-independent twin arginine protein secretion motifs, and the absence of certain canonical signal recognition particle proteins from all Leptospira; and 7) and demonstration of infectious Leptospira-specific signal-responsive gene expression, motility and chemotaxis systems. By identifying large scale changes in infectious (pathogenic and intermediately pathogenic) vs. non-infectious Leptospira, this work provides new insights into the evolution of a genus of bacterial pathogens. This work will be a comprehensive roadmap for understanding leptospirosis pathogenesis. More generally, it provides new insights into mechanisms by which bacterial pathogens adapt to mammalian hosts.

Moringa oleifera is a promising plant species for oil and forage, but its genetic improvement is limited. Our current breeding program in this species focuses on exploiting the functional genes associated with important agronomical traits. Here, we screened reliable reference genes for accurately quantifying the expression of target genes using the technique of real-time quantitative polymerase chain reaction (RT-qPCR) in M. oleifera. Eighteen candidate reference genes were selected from a transcriptome database, and their expression stabilities were examined in 90 samples collected from the pods in different developmental stages, various tissues, and the roots and leaves under different conditions (low or high temperature, sodium chloride (NaCl)- or polyethyleneglycol (PEG)- simulated water stress). Analyses with geNorm, NormFinder and BestKeeper algorithms revealed that the reliable reference genes differed across sample designs and that ribosomal protein L1 (RPL1) and acyl carrier protein 2 (ACP2) were the most suitable reference genes in all tested samples. The experiment results demonstrated the significance of using the properly validated reference genes and suggested the use of more than one reference gene to achieve reliable expression profiles. In addition, we applied three isotypes of the superoxide dismutase (SOD) gene that are associated with plant adaptation to abiotic stress to confirm the efficacy of the validated reference genes under NaCl and PEG water stresses. Our results provide a valuable reference for future studies on identifying important functional genes from their transcriptional expressions via RT-qPCR technique in M. oleifera.

Pathogenic spirochetes cause clinically relevant diseases in humans and animals, such as Lyme disease and leptospirosis. The causative agent of Lyme disease, Borrelia burgdorferi, and the causative agent of leptospirosis, Leptospria interrogans, encounter reactive oxygen species (ROS) during their enzootic cycles. This report demonstrated that physiologically relevant concentrations of pyruvate, a potent H2O2 scavenger, and provided passive protection to B. burgdorferi and L. interrogans against H2O2. When extracellular pyruvate was absent, both spirochetes were sensitive to a low dose of H2O2 (≈0.6 µM per h) generated by glucose oxidase (GOX). Despite encoding a functional catalase, L. interrogans was more sensitive than B. burgdorferi to H2O2 generated by GOX, which may be due to the inherent resistance of B. burgdorferi because of the virtual absence of intracellular iron. In B. burgdorferi, the nucleotide excision repair (NER) and the DNA mismatch repair (MMR) pathways were important for survival during H2O2 challenge since deletion of the uvrB or the mutS genes enhanced its sensitivity to H2O2 killing; however, the presence of pyruvate fully protected ΔuvrB and ΔmutS from H2O2 killing further demonstrating the importance of pyruvate in protection. These findings demonstrated that pyruvate, in addition to its classical role in central carbon metabolism, serves as an important H2O2 scavenger for pathogenic spirochetes. Furthermore, pyruvate reduced ROS generated by human neutrophils in response to the Toll-like receptor 2 (TLR2) agonist zymosan. In addition, pyruvate reduced neutrophil-derived ROS in response to B. burgdorferi, which also activates host expression through TLR2 signaling. Thus, pathogenic spirochetes may exploit the metabolite pyruvate, present in blood and tissues, to survive H2O2 generated by the host antibacterial response generated during infection.

The Kaiser effect (KE), as a presentation of rock stress memory, has been widely used in in situ stress measurement because of its convenience and economy. However, the influence of rock lithology and directionality on the KE have not been answered yet. To solve this question, three-stage loading Brazilian tests were conducted on three types of rock disks in this study. The specimens were rotated with a certain rotation angle? (5°-90°) before the third-stage loading, and the jump point method and bilinear regression method were selected to recognize the Kaiser points. The results suggested that significant KE occurred in the three rock materials under the Brazilian test and that the KE directionality of rocks with different lithology varies greatly. The KE gradually fails as the rotation angle increases. The critical angles of granite, marble, and sandstone are 13°, 60°, and 5°, respectively. Besides, the directionality of the KE is closely related to the distribution of microcracks inside the rock and the critical stress of crack propagation. This study could provide a reference for experimental design and error analysis of in situ stress measurement by the acoustic emission method in civil and geotechnical engineering. [ABSTRACT FROM AUTHOR]

Metagenomic analysis of mosquito-borne and mosquito-specific viruses is useful to understand the viral diversity and for the surveillance of pathogens of medical and veterinary importance. Yunnan province is located at the southwest of China and has rich abundance of mosquitoes. Arbovirus surveillance is not conducted regularly in this province particularly at animal farms, which have public health as well as veterinary importance. Here, we have analyzed 10 pools of mosquitoes belonging to Culex tritaeniorhyncus, Aedes aegypti, Anopheles sinensis, and Armigeres subalbatus species, collected from different animal farms located at Yunnan province of China by using metagenomic next-generation sequencing technique. The generated viral metagenomic data reveal that the viral community matched by the reads was highly diverse and varied in abundance among animal farms, which contained more than 19 viral taxonomic families, specific to vertebrates, invertebrates, fungi, plants, protozoa, and bacteria. Additionally, a large number of viral reads were related to viruses that are non-classified. The viral reads related to animal viruses included parvoviruses, anelloviruses, circoviruses, flaviviruses, rhabdoviruses, and seadornaviruses, which might be taken by mosquitoes from viremic animal hosts during blood feeding. Notably, the presence of viral reads matched with Japanese encephalitis virus, Getah virus, and porcine parvoviruses in mosquitoes collected from different geographic sites suggested a potential circulation of these viruses in their vertebrate hosts. Overall, this study provides a comprehensive knowledge of diverse viral populations present at animal farms of Yunnan province of China, which might be a potential source of diseases for humans and domestic animals. [ABSTRACT FROM AUTHOR]