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Contribution: This study examined the role of the engineering and smartness identities of three women as they made decisions about their participation in engineering majors. In addressing the under-representation of women in engineering, particularly in electrical engineering and computer science fields where they have been extremely under-represented, it is important to consider engineering identity as it has been shown to be an important component of major selection and persistence. Background: Smartness is inextricably linked to engineering and prior work has shown that identifying as smart is salient to students who choose engineering majors. However, the relative roles of students' engineering and smartness identities as they relate to academic decision making and persistence in engineering is not well understood. Research Question: How do engineering identity and smartness identity relate to women's decisions about choosing engineering majors in the instances of joining engineering, changing engineering major, and leaving engineering? Methodology: Data were collected from a series of three interviews with three different women. Data condensation techniques, including writing participant summary memos and analytic memos, focused on detailing participants' academic decisions, engineering identity, and smartness identity were used for analysis. Data visualization was used to map the women's engineering identity and smartness identity to their academic decisions related to their majors. Findings: The findings indicate the participants' smartness identity was salient in the initial decision to matriculate into engineering, both their engineering and smartness identities remained stable as they persisted in or left engineering. And reveal complex interactions between these identities and decision making.

Abstract Background The presence of sensory impairment among older age cohorts exerts a significant impact on both individuals and society generally. Although the impact of dietary patterns on health is vital across all stages of life, there still a paucity of comprehensive research on the association between dietary variety and sensory impairments. Objective To investigate the potential relationship between dietary diversity and the prevalence of visual and hearing impairment or dual sensory impairments (visual and hearing impairment) among the oldest old population. Methods This is a cross-sectional study relied on data obtained from the 2018 survey conducted by the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Subjects aged 80 and older with complete vision and hearing data were included in the study. Multivariate logistic regression models were developed to examine the association between dietary components and visual and hearing impairment while controlling for age, gender, socioeconomic demographic factors, living habits, other food habits, and general health status. Results The study included 10,093 participants, with an average age of 92.29 ± 7.75 years. Vision and hearing function were assessed based on the ability to distinguish the direction of the break in the circle and the requirement for hearing aids, respectively. Upon controlling for confounding variables, individuals with a greater Dietary Diversity Score (DDS, the number of food groups, range: 1–11) had a reduced likelihood of experiencing visual impairment (odds ratio [OR] = 0.944, 95% confidence interval [CI], 0.915—0.974) and dual sensory impairment (OR = 0.930, 95% CI, 0.905—0.955). In comparison to the low dietary variety group (insufficient dietary diversity, DDS

Abstract Introduction Non-ophthalmologists often lack sufficient operational training to use a direct ophthalmoscope proficiently, resulting in a global deficit of basic ophthalmological skills among general practitioners. This deficiency hampers the timely diagnosis, referral, and intervention of patients. Consequently, the optimization of teaching tools and methods to enhance teaching efficiency is imperative. This study explores the effectiveness of the Eyesi Direct Ophthalmoscope Simulator (Eyesi) as an innovative tool for fundus examination training. Methods Medical undergraduates were randomly assigned to Group A or B (n = 168). All participants completed a pre-training questionnaire. Group A received Eyesi training, while Group B underwent traditional direct ophthalmoscope (TDO) training. Subsequently, participants answered questionnaires relevant to their respective training methods. Both groups exchanged training tools and completed a summary questionnaire. Results After training, 54.17% of participants believed that images presented by the Eyesi were consistent with the real fundus. Group A scored significantly higher than Group B in fundus structure recognition and self-confidence in examination. The degree of mastery over fundus theory score increased from 6.10 ± 0.13 to 7.74 ± 0.16 (P

This paper addresses the ignition compatibility issues of the water ramjet engine (WRE). It studies the impact of several engine parameters on the ignition process and performance, including the primary water injection angle, primary water-fuel ratio, igniter mass, and igniter position. Based on the specified parameters, a multiphase flow computational model for the ignition process of the WRE developed. The obtained results show that the ignition performance of the engine is significantly affected by the primary water-fuel ratio, igniter mass, and igniter location. When the primary water-fuel ratio increases, the equilibrium temperature in the combustion chamber tends to initially increase and then decrease, reaching a maximum value for a ratio of 0.55. Criteria are then proposed to determine whether the WRE can transition into the self-sustained combustion phase. These ignition criteria are established by considering the relationship between the mass of the igniter charge, its location, and the surface area of the burning surface of the propellant. The results obtained by the proposed model demonstrate that the engine will not extinguish when this value is greater than 46.65.

This study presents a novel method to assess the learning effectiveness using Electroencephalography (EEG)-based deep learning model. It is difficult to assess the learning effectiveness of professional courses in cultivating students’ ability objectively by questionnaire or other assessment methods. Research in the field of brain has shown that innovation ability can be reflected from cognitive ability which can be embodied by EEG signal features. Three navigation tasks of increasing cognitive difficulty were designed and a total of 41 subjects participated in the experiment. For the classification and tracking of the subjects’ EEG signals, a convolutional neural network (CNN)-based Multi-Time Scale Spatiotemporal Compound Model (MTSC) is proposed in this paper to extract and classify the features of the subjects’ EEG signals. Furthermore, Spiking neural networks (SNN) -based NeuCube is used to assess the learning effectiveness and demonstrate cognitive processes, acknowledging that NeuCube is an excellent method to display the spatiotemporal differences between spikes emitted by neurons. The results of the classification experiment show that the cognitive training traces of different students in solving three navigational problems can be effectively distinguished. More importantly, new information about navigation is revealed through the analysis of feature vector visualization and model dynamics. This work provides a foundation for future research on cognitive navigation and the training of students’ navigational skills.

Abstract Background Obstructive shock is extremely rare in clinical practice and is caused by acute blood flow obstruction in the central vessels of either the systemic or pulmonary circulation. Utilizing inferior vena cava filters (IVCFs) to prevent pulmonary embolism (PE) is associated with some potential complications, such as inferior vena cava thrombosis (IVCT). Shock as a direct result of IVCT is rare. We present a case of obstructive shock secondary to extensive IVCT caused by inadequate anticoagulant therapy after the placement of an IVCF. Case presentation A 63-year-old male patient with a traffic accident injury presented orthopaedic trauma and lower limb deep vein thrombosis (DVT). He experienced sudden and severe abdominal pain with hypotension, tachycardia, tachypnea, oliguria and peripheral oedema 5 days after IVCF placement and 3 days after cessation of anticoagulant therapy. Considering that empirical anti-shock treatment lasted for a while and the curative effect was poor, we finally recognized the affected vessels and focused on the reason for obstructive shock through imaging findings—inferior vena cava thrombosis and occlusion. The shock state immediately resolved after thrombus aspiration. The same type of shock occurred again 6 days later during transfer from the ICU to general wards and the same treatment was administered. The patient recovered smoothly in the later stage, and the postoperative follow-up at 1, 3, and 12 months showed good results. Conclusion This case alerts clinicians that it is crucial to ensure adequate anticoagulation therapy after IVCF placement, and when a patient presents with symptoms such as hypotension, tachycardia, and lower limb and scrotal oedema postoperatively, immediate consideration should be given to the possibility of obstructive shock, and prompt intervention should be based on the underlying cause.

IntroductionAtherosclerosis, a leading cause of global cardiovascular mortality, is characterized by chronic inflammation. Central to this process is the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome, which significantly influences atherosclerotic progression. Recent research has identified that the olfactory receptor 2 (Olfr2) in vascular macrophages is instrumental in driving atherosclerosis through NLRP3- dependent IL-1 production.MethodsTo investigate the effects of Corilagin, noted for its anti-inflammatory attributes, on atherosclerotic development and the Olfr2 signaling pathway, our study employed an atherosclerosis model in ApoE−/− mice, fed a high-fat, high-cholesterol diet, alongside cellular models in Ana-1 cells and mouse bone marrow-derived macrophages, stimulated with lipopolysaccharides and oxidized low-density lipoprotein.ResultsThe vivo and vitro experiments indicated that Corilagin could effectively reduce serum lipid levels, alleviate aortic pathological changes, and decrease intimal lipid deposition. Additionally, as results showed, Corilagin was able to cut down expressions of molecules associated with the Olfr2 signaling pathway.DiscussionOur findings indicated that Corilagin effectively inhibited NLRP3 inflammasome activation, consequently diminishing inflammation, macrophage polarization, and pyroptosis in the mouse aorta and cellular models via the Olfr2 pathway. This suggests a novel therapeutic mechanism of Corilagin in the treatment of atherosclerosis.

Abstract Tumor‐associated thrombus (TAT) accounts for a high proportion of venous thromboembolism. Traditional thrombolysis and anticoagulation methods are not effective due to various complications and contraindications, which can easily lead to patients dying from TAT rather than the tumor itself. These clinical issues demonstrate the need to research diverse pathways for adjuvant thrombolysis in antitumor therapy. Previously, the phenotypic and functional transformation of monocytes/macrophages is widely reported to be involved in intratribal collagen regulation. This study finds that myeloid deficiency of the oncogene SHP2 sensitizes Ly6Clow monocyte/macrophage differentiation and can alleviate thrombus organization by increasing thrombolytic Matrix metalloproteinase (MMP) 2/9 activities. Moreover, pharmacologic inhibition by SHP099, examined in mouse lung metastatic tumor models, reduces tumor and thrombi burden in tumor metastatic lung tissues. Furthermore, SHP099 increases intrathrombus Ly6Clow monocyte/macrophage infiltration and exhibits thrombolytic function at high concentrations. To improve the thrombolytic effect of SHP099, NanoSHP099 is constructed to achieve the specific delivery of SHP099. NanoSHP099 is identified to be simultaneously enriched in tumor and thrombus foci, exerting dual tumor‐suppression and thrombolysis effects. NanoSHP099 presents a superior thrombus dissolution effect than that of the same dosage of SHP099 because of the higher Ly6Clow monocyte/macrophage proportion and MMP2/MMP9 collagenolytic activities in organized thrombi.

Abstract Diabetes mellitus, known for its complications, especially vascular complications, is becoming a globally serious social problem. Atherosclerosis has been recognized as a common vascular complication mechanism in diabetes. The diacylglycerol (DAG)–protein kinase C (PKC) pathway plays an important role in atherosclerosis. PKCs can be divided into three subgroups: conventional PKCs (cPKCs), novel PKCs (nPKCs), and atypical PKCs (aPKCs). The aim of this review is to provide a comprehensive overview of the role of the PKCδ pathway, an isoform of nPKC, in regulating the function of endothelial cells, vascular smooth muscle cells, and macrophages in diabetic atherosclerosis. In addition, potential therapeutic targets regarding the PKCδ pathway are summarized. Video Abstract

Abstract Background Drosophila melanogaster is excellent animal model for understanding the molecular basis of human neurological and motor disorders. The experimental conditions and chamber design varied between studies. Moreover, most previously established paradigms focus on fly trace detection algorithm development. A comprehensive understanding on how fly behaves in the chamber is still lacking. Results In this report, we established 74 unique behavior metrics quantifying spatiotemporal characteristics of adult fly locomotion and social behaviors, of which 49 were newly proposed. By the aiding of the developed analysis pipeline, Drosophila video tracking (DVT), we identified siginificantly different patterns of fly behavior confronted with different chamber height, fly density, illumination and experimental time. Meanwhile, three fly strains which are widely used as control lines, Canton-S(CS), w 1118 and Oregon-R (OR), were found to exhibit distinct motion explosiveness and exercise endurance. Conclusions We believe the proposed behavior metrics set and pipeline should help identify subtle spatial and temporal differences of drosophila behavior confronted with different environmental factors or gene variants.

To overcome the issue of unstable speed output encountered by cotton pickers operating in harsh environments and subject to frequent external load fluctuations, a hydraulic–mechanical transmission (HMT) for cotton pickers is proposed in this study. By analyzing the driving system of the cotton picker, a Lavira-based HMT scheme is developed. The matching characteristics of the HMT speed ratio are analyzed, a continuity and smoothness test of the speed ratio of the changing segment is carried out, and the influence law of smoothness of the HMT changing segment is discussed. The results show that the HMT system effectively satisfies the driving speed requirements for both field harvesting and road transportation of cotton pickers. The HMT speed ratio is continuously controllable and the design is reasonable. The HMT load torque and the oil pressure in the main oil circuit have a significant impact on the smoothness indicators of speed reduction and dynamic load. Additionally, the flow rate of the governor valve has a notable effect on the smoothness indicator of sliding friction power. However, the engine’s output speed has no significant influence on the HMT’s smoothness. This research can provide theoretical support for the development and design of cotton picker gearboxes and the transmission characteristics and experimental research of off-road vehicle gearboxes.

Atherosclerosis is a common form of cardiovascular disease, which is one of the most prevalent causes of death worldwide, particularly among older individuals. Surgery is the mainstay of treatment for severe stenotic lesions, though the rate of restenosis remains relatively high. Current medication therapy for atherosclerosis has limited efficacy in reversing the formation of atherosclerotic plaques. The search for new drug treatment options is imminent. Some potent medications have shown surprising therapeutic benefits in inhibiting inflammation and endothelial proliferation in plaques. Unfortunately, their use is restricted due to notable dose-dependent systemic side effects or degradation. Nevertheless, with advances in nanotechnology, an increasing number of nano-related medical applications are emerging, such as nano-drug delivery, nano-imaging, nanorobots, and so forth, which allow for restrictions on the use of novel atherosclerotic drugs to be lifted. This paper reviews new perspectives on the targeted delivery of nanoparticles to blood vessels for the treatment of atherosclerosis in both systemic and local drug delivery. In systemic drug delivery, nanoparticles inhibit drug degradation and reduce systemic toxicity through passive and active pathways. To further enhance the precise release of drugs, the localized delivery of nanoparticles can also be accomplished through blood vessel wall injection or using endovascular interventional devices coated with nanoparticles. Overall, nanotechnology holds boundless potential for the diagnosis and treatment of atherosclerotic diseases in the future.

To achieve a comprehensive and accurate diagnosis of faults in rolling bearings, a method for diagnosing rolling bearing faults has been proposed. This method is based on Multivariate Variational Mode Decomposition (MVMD) signal reconstruction, Multivariate Multiscale Dispersion Entropy (MMDE)-Generalized Normal Distribution Optimization (GNDO), and Marine predators’ algorithm-based optimization support vector machine (MPA-SVM). Firstly, by using a joint evaluation function (energy*|correlation coefficient|), the multi-channel vibration signals of rolling bearings after MVMD decomposition are denoised and reconstructed. Afterward, MMDE is applied to fuse the information from the reconstructed signal and construct a high-dimensional fault feature set. Following that, GNDO is used to select features and extract a subset of low-dimensional features that are sensitive and easy to classify. Finally, MPA is used to realize the adaptive selection of important parameters in the SVM classifier. Fault diagnosis experiments are carried out using datasets provided by the Case Western Reserve University (CWRU) and Paderborn University (PU). The MVMD signal reconstruction method can effectively filter out the noise components of each channel. MMDE-GNDO can availably mine multi-channel fault features and eliminate redundant (or interference) items. The MPA-SVM classifier can identify faults in different working conditions with an average accuracy of 99.72% and 100%, respectively. The results demonstrate the accuracy, efficiency, and stability of the proposed method.

Rechargeable aqueous zinc-iodine (Zn-I2) batteries are generally in the form of redox flow battery that uses an ion-selective membrane to separate two different electrolytes. The reversible redox reactions of iodine species in the electrolyte play a key role in charge and discharge. If without the ion-selective membrane, the Zn anode would suffer from severe corrosion, and the interaction between Zn and I3– in the cycling process gradually reduces the cell capacity, Coulombic efficiency, and cycle life. Here, a simple and scalable chemical bath deposition method is developed to form an amorphous Se overlayer on the Zn foil, thus remarkably improving its anode performance in aqueous Zn-I2 battery and ruling out the use of ion-selective membrane. Effects of Se deposition time on the anti-corrosion performance, rate performance, capacity, and cycle life are investigated in detail. As a result, the button-type full cell using optimized Zn@Se anode delivers high Coulombic efficiency of 99.4%, high specific capacity of 180 mAh g–1, and ultra-long lifespan over 50,000 cycles with a capacity retention of 82.6%. Pouch type cells are made to demonstrate the efficient suppression of hydrogen gas evolution. To manifest the potential for practical applications, high-capacity cells using plastic boxes are made to drive an electric fan and a robot toy. Mechanism of this amorphous Se overlayer on Zn anode in enhancing the battery performance is discussed.

Arteriovenous fistulas (AVFs) have long been used as dialysis access in patients with end-stage renal disease; however, their maturation and long-term patency still fall short of clinical needs. Rodent models are irreplaceable to facilitate the study of mechanisms and provide reliable insights into clinical problems. The ideal rodent AVF model recapitulates the major features and pathology of human disease as closely as possible, and pre-induction of the uremic milieu is an important addition to AVF failure studies. Herein, we review different surgical methods used so far to create AVF in rodents, including surgical suturing, needle puncture, and the cuff technique. We also summarize commonly used evaluations after AVF placement. The aim was to provide recent advances and ideas for better selection and induction of rodent AVF models. At the same time, further improvements in the models and a deeper understanding of AVF failure mechanisms are expected.

For suppressing the self-corrosion rate of the anode of aluminum-air battery and improving its discharge performance，the effects of adding sodium polyacrylate (PAAS) or zinc oxide (ZnO) alone or adding them both on the self-corrosion and discharge properties of aluminum alloy in 4mol/L NaOH solution were studied using 6061 aluminum alloy as anode material.Results showed that the effect of PAAS/ZnO composite corrosion inhibitor was better than that of single corrosion inhibitor.The composite corrosion inhibitor not only promoted the activation of the anode，but also formed a more stable composite protective film on the surface of aluminum anode，which effectively slowed down the selfcorrosion of hydrogen evolution and improved the utilization rate of the anode.In NaOH+PAAS+ZnO electrolytic liquid system，the dissolution of 6061 aluminum alloy was mainly controlled by the diffusion of charge in corrosion products or zinc salt deposition layer.After adding the composite corrosion inhibitor，the self - corrosion rate of 6061 aluminum alloy decreased from 0.496 4 mg/(cm2 ·min) to 0.275 0 mg/(cm2·min).Meanwhile，the inhibition rate reached 44.6%，the discharge voltage decreased from -1.381 V to -1.681 V，and the anode utilization rate increased by 13.5%.In general，the discharge performance of aluminum-air battery was obviously improved.

[INLINE:1] Vision depends on accurate signal conduction from the retina to the brain through the optic nerve, an important part of the central nervous system that consists of bundles of axons originating from retinal ganglion cells. The mammalian optic nerve, an important part of the central nervous system, cannot regenerate once it is injured, leading to permanent vision loss. To date, there is no clinical treatment that can regenerate the optic nerve and restore vision. Our previous study found that the mobile zinc (Zn2+) level increased rapidly after optic nerve injury in the retina, specifically in the vesicles of the inner plexiform layer. Furthermore, chelating Zn2+ significantly promoted axonal regeneration with a long-term effect. In this study, we conditionally knocked out zinc transporter 3 (ZnT3) in amacrine cells or retinal ganglion cells to construct two transgenic mouse lines (VGATCreZnT3fl/fl and VGLUT2CreZnT3fl/fl, respectively). We obtained direct evidence that the rapidly increased mobile Zn2+ in response to injury was from amacrine cells. We also found that selective deletion of ZnT3 in amacrine cells promoted retinal ganglion cell survival and axonal regeneration after optic nerve crush injury, improved retinal ganglion cell function, and promoted vision recovery. Sequencing analysis of reginal ganglion cells revealed that inhibiting the release of presynaptic Zn2+ affected the transcription of key genes related to the survival of retinal ganglion cells in postsynaptic neurons, regulated the synaptic connection between amacrine cells and retinal ganglion cells, and affected the fate of retinal ganglion cells. These results suggest that amacrine cells release Zn2+ to trigger transcriptomic changes related to neuronal growth and survival in reginal ganglion cells, thereby influencing the synaptic plasticity of retinal networks. These results make the theory of zinc-dependent retinal ganglion cell death more accurate and complete and provide new insights into the complex interactions between retinal cell networks.

Tobamoviruses are a group of plant viruses that pose a significant threat to agricultural crops worldwide. In this review, we focus on plant immunity against tobamoviruses, including pattern-triggered immunity (PTI), effector-triggered immunity (ETI), the RNA-targeting pathway, phytohormones, reactive oxygen species (ROS), and autophagy. Further, we highlight the genetic resources for resistance against tobamoviruses in plant breeding and discuss future directions on plant protection against tobamoviruses.

It has been known for decades that the incidence of chronic lymphocytic leukemia (CLL) is significantly lower in Asia than in Western countries, but the reason responsible for this difference still remains a major knowledge gap. Using GeneChip® miRNA array to analyze the global microRNA expression in B lymphocytes from Asian and Western CLL patients and healthy individuals, we have identified microRNA with CLL-promoting or suppressive functions that are differentially expressed in Asian and Western individuals. In particular, miR-4485 is upregulated in CLL patients of both ethnic groups, and its expression is significantly lower in Asian healthy individuals. Genetic silencing of miR-4485 in CLL cells suppresses leukemia cell growth, whereas ectopic expression of miR-4485 promotes cell proliferation. Mechanistically, miR-4485 exerts its CLL-promoting activity by inhibiting the expression of TGR5 and activating the ERK1/2 pathway. In contrast, miR-138, miR-181a, miR- 181c, miR-181d, and miR-363 with tumor-suppressive function are highly expressed in Asian healthy individuals. Our study suggests that differential expression of several important microRNA with pro- or anti-CLL functions in Asian and Western B lymphocytes likely contributes to the difference in CLL incidence between the two ethnic groups, and that miR-4485 and its downstream molecule TGR5 could be potential therapeutic targets.

Abstract Background Schwannomas are benign tumors deriving from the sheath of cranial and peripheral nerves. The vagus nerve is comprised of a complex neuro-endocrine-immune network that maintains homeostasis, most tracts of it play a role in parasympathetic activity. We present an example of a rare cervical vagal schwannoma case accompanied by arrhythmia. Case presentation A 35-year-old female patient with a left cervical vagus schwannoma and ventricular arrhythmia underwent schwannoma resection in the operating room. The patient’s suppressed heart rate increased after tumor removal, and the cardiac rhythm returned to normal postoperatively. Pathological examination demonstrated the diagnosis of schwannoma. Conclusions This case explains the link between the vagus nerve and the cardiovascular system, proving that a damaged cervical vagus nerve can inhibit the heart rate and lead to arrhythmias, and eventually requiring surgical intervention.

In order to obtain lignin with low molecular weight and polydispersity, as well as high antioxidant activity, using Camellia oleifera shell as raw material, four lignin products were isolated from it by alkaline and deep eutectic solvents. The structural and pyrolysis properties of lignin were investigated with ultraviolet spectroscopy (UV), Fourier transform infrared spectroscopy (FTIR), gel permeation chromatography (GPC) and thermogravimetric analyzer (TGA). Furthermore, the antioxidant activity of the lignin samples was evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity assay. The UV and FTIR analyses showed that the lignin from Camellia oleifera shell was mainly composed of guaiacyl and syringyl. GPC analysis revealed that AL had a relatively higher molecular weight (Mw=41858 g/mol) and broad polydispersity index (PDI=4.53), and the DES-lignin exhibited relatively low relative molecular weight (MwAL>ChCl-EG-P>ChCl-GA. Furthermore, the results showed that four lignin products had good antioxidant activity in vitro, and the IC50 values of DPPH free radical scavenging ability was 0.388~1.02 mg/mL. The findings of this study would provide a novel way to fractionate lignin from Camellia oleifera shell, and provide certain reference value for the development of lignin valorization.

Objective To summarize the experience and effect using 3D parametric surface planar topological guide plate technology in fenestrated/branched endovascular aortic repair (F/B EVAR) to repair aortic arch and thoracoabdominal aortic lesions involving important aortic branches. Methods From August 2020 through April 2022, 17 patients [14 males and 3 females, mean age of(61.06±11.23)(39-78) years] with complex aortic lesions involving important branches were treated in both Nanjing Drum Tower Hospital and Union Hospital. There were 8 cases with aortic arch aneurysms 4 cases and dissections 4 cases, respectively, and 9 cases with thoracoabdominal aortic aneurysms 5 cases and dissections 4 cases, respectively. Six cases were urgent operation and 11 cases were selective operation. Before operation, 3D parametric surface planar topological guide plate was made according to aortic computed tomography angiography. Under the guidance of planar guide plate, pre-fenestrated and external/internal branched and other endovascular aortic repair was performed. Totally, 50 fenestrated/branched stent grafts were planted. Results All operations were completed without conversion to open surgery. Average operative time was (4.57±2.29)(1.50-10.67) h. There was no renal insufficiency, paraplegia and loss of branch arteries. One patient (5.88%) died during perioperative period. Within the follow-up, there were 2 cases (11.76%) of endoleak type Ⅰc and type Ⅲc, respectively. Conclusions F/B EVAR under the guidance of 3D parametric surface planar topological guide plate is a minimally invasive treatment. The technology is more accurate than traditional measurement and positioning, faster than 3D printing guidance, and safe and reliable shown in the follow-up.

Objective The current study aimed to investigate the prognosis and treatment of primary cutaneous angiosarcoma (PCA) and primary subcutaneous angiosarcoma (PSCA), and tried to develop a prognostic nomogram model of them. Methods A total of 1763 cases retrieved from the Surveillance, Epidemiology, and End Results (SEER) database were retrospectively analyzed. Survival analyses were performed to explore the prognosis of patients and the effects of different treatment methods. All data were randomly allocated into a training set and a testing set to develop and validate the nomogram model. Results The findings showed that age, sex, grade, tumor size, multiple primary malignant tumors, stage, primary site surgery (PSS), radiotherapy (RT), and chemotherapy (CT) were correlated with prognosis (p

(1) Background: Arteriovenous fistulas (AVFs) are the preferred site for hemodialysis. Unfortunately, approximately 60% of patients suffer from AVF failure within one year. Oxidative stress plays an important role in the occurrence and development of AVF. However, the underlying mechanisms remain unclear. Therefore, specific oxidative stress-related biomarkers are urgently needed for the diagnosis and treatment of AVF failure. (2) Methods: Bioinformatics analysis was carried out on dataset GSE119296 to screen for PTGS2 as a candidate gene related to oxidative stress and to verify the expression level and diagnostic efficacy of PTGS2 in clinical patients. The effects of NS398, a PTGS2 inhibitor, on hemodynamics, smooth muscle cell proliferation, migration, and oxidative stress were evaluated in a mouse AVF model. (3) Results: Based on 83 oxidative stress-related differentially expressed genes, we identified the important pathways related to oxidative stress. PTGS2 may have diagnostic and therapeutic efficacy for AVF failure. We further confirmed this finding using clinical specimens and validation datasets. The animal experiments illustrated that NS398 administration could reduce neointimal area (average decrease: 49%) and improve peak velocity (average increase: 53%). (4) Conclusions: Our study identified PTGS2 as an important oxidative stress-related biomarker for AVF failure. Targeting PTGS2 reduced oxidative stress and improved hemodynamics in an AVF mouse model.

Abstract Tyrosine kinase inhibitors (TKIs) such as imatinib (IM) are key drugs for treatment of chronic myeloid leukemia (CML). Development of drug resistance to TKIs due to BCR-ABL mutation, especially T315I mutation, poses a major challenge in the clinical treatment of CML. The purpose of this study was to test metabolic modulation as a potential strategy to overcome imatinib resistance based on the possible crosstalk between BCR-ABL signaling and metabolic changes in CML. 2-deoxy-d-glucose (2-DG) was used to modulate the glucose metabolism in CML cells sensitive to IM (KBM5 cell line) and resistant to imatinib with BCR-ABL T315I mutation (KBM5-T315I cell line). Seahorse XFe24 extracellular flux analyzer to quantify oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) was used to measure cellular energy metabolism. Cell proliferation was analyzed by CCK-8 assay and MTS assay. Annexin V/PI staining was used to evaluate cell apoptosis. Autophagy-related proteins and enzyme/proteins were detected by Western blotting. Cellular ATP concentration was detected using an ATP-based Cell Titer Kit. The combined action of 2-DG and IM was evaluated by calculating the drug combination index. Our results found that inhibition of glucose metabolism by 2-DG significantly impaired the viability of CML cells and co-treatment with 2-DG and imatinib induced a synergistic inhibition of KBM5 and KBM5-T315I cells. 2-DG induced cell death by autophagy, not by apoptosis, as evidenced by increased expression of Beclin1 and LC3AII and lack of annexin V/PI-positive cells. At the biochemical level, 2-DG inhibited glycolysis and mitochondrial oxygen consumption manifested by a significant decrease in ECAR and OCR, and a depletion of ATP. The severe metabolic stress induced by 2-DG in CML cells led to autophagic cell death. Our results suggested a metabolic vulnerability of CML cells that could be targeted by a combination of 2-DG and imatinib as an alternative treatment for imatinib-resistant CML.

Summary Two phenazine compounds, diastaphenazine and izumiphenazine C, with complex structures and promising antitumour activity have been isolated from the plant endophytic actinomycete Streptomyces diastaticus W2. Their putative biosynthetic gene cluster (dap) was identified by heterologous expression and gene knockout. There are twenty genes in the dap cluster. dap14‐19 related to shikimic pathway were potentially involved in the precursor chorismic acid biosynthesis, and dapBCDEFG were confirmed to be responsible for the biosynthesis of the dibenzopyrazine ring, the nuclear structure of phenazines. Two transcriptional regulatory genes dapR and dap4 played the positive regulatory roles on the phenazine biosynthetic pathway. Most notably, the dimerization of the dibenzopyrazine ring in diastaphenazine and the loading of the complex side chain in izumiphenazine C could be catalysed by the cyclase homologous gene dap5, suggesting an unusual modification strategy tailoring complex phenazine biosynthesis. Moreover, metabolite analysis of the gene deletion mutant strain S. albus::23C5Δdap2 and substrate assay of the methyltransferase Dap2 clearly revealed the biosynthetic route of the complex side chain in izumiphenazine C.

SIPRα on macrophages binds with CD47 to resist proengulfment signals, but how the downstream signal of SIPRα controls tumor-infiltrating macrophages (TIMs) is still poorly clarified. Here, we report that the CD47/signal regulatory protein α (SIRPα) axis requires the deneddylation of tyrosine phosphatase SHP2. Mechanistically, Src homology region 2–containing protein tyrosine phosphatase 2 (SHP2) was constitutively neddylated on K358 and K364 sites; thus, its autoinhibited conformation was maintained. In response to CD47-liganded SIRPα, SHP2 was deneddylated by sentrin-specific protease 8 (SENP8), which led to the dephosphorylation of relevant substrates at the phagocytic cup and subsequent inhibition of macrophage phagocytosis. Furthermore, neddylation inactivated myeloid-SHP2 and greatly boosted the efficacy of colorectal cancer (CRC) immunotherapy. Importantly, we observed that supplementation with SHP2 allosteric inhibitors sensitized immune treatment–resistant CRC to immunotherapy. Our results emphasize that the CRC subtype that is unresponsive to immunotherapy relies on SIRPαhiSHP2hiNEDD8lo TIMs and highlight the need to further explore the strategy of SHP2 targeting in CRC therapy.

BackgroundSignet-ring cell gastric carcinoma is a highly malignant tumor, with the characteristics of strong invasiveness, rapid progression, a high degree of malignancy, and generally poor prognosis. The most common site of metastases is the abdominal organs, especially the liver, while delayed cutaneous metastases are rare.Case presentationWe report a case of cutaneous metastases on the head, groin, and thigh, which recurred 7 years after signet-ring cell gastric carcinoma surgery. The patient was diagnosed with a 2.0×1.5×1.0cm tumor at the angle of stomach, and treated with Billroth II distal gastrectomy accompanied with D2 lymph node dissection. According the pathology, the stage was pT1N3M0. Then the patient received two cycles of oxaliplatin and tegafur chemotherapy, which was discontinued due to the inability to tolerate the side effects of chemotherapy. Seven years after the surgery, the patient initially presented with a fleshy mass on the head and beaded nodules in the groin; then, the mass gradually became larger, along with the thighs turning red, swollen, and crusty. Firstly, the patient was diagnosed with “lower extremity lymphangitis” and treated mostly with anti-inflammatory, promote lymphatic return, detumescence and elastic force cannula in vascular surgery department. However, the symptoms relieved insufficient. Finally, the skin biopsy indicates a signet-ring cell gastric carcinoma cutaneous metastasis. The whole-body PET-CT examination showed multiple nodules with increased metabolism. Then the patient was transferred to The Department of Oncology for further chemotherapy.ConclusionOur case highlights that gastric tumor recurrence and metastasis should be highly suspected when skin lesions appear in patients with signet-ring cell gastric carcinoma. At the same time, multidisciplinary consultation and close cooperation between surgeons, oncologists, and dermatologists are of great significance to the diagnosis and treatment of this disease.

Hydrogel-based micro-tissue engineering technique, a bottom-up approach, is promising in constructing soft tissue of large size with homogeneous spatial distribution and superior regeneration capacity compared to the top-down approach. However, most of the studies employed micro-tissues with simple mesenchymal stem cells, which could hardly meet the growth of matrix and vessels. Therefore, we recommend a dual micro-tissues assembly strategy to construct vascularized tissue-engineered breast grafts (TEBGs). Adipose micro-tissues (AMs) and vessel micro-tissues (VMs) were fabricated by seeding adipose-derived stem cells (ADSCs) and human umbilical vein endothelial cells (HUVECs) on collagen microgels (COLs) with a uniform diameter of ∼250 ​μm, respectively. TEBGs were constructed by injecting the dual micro-tissues into 3D printed breast-like Thermoplastic Urethane (TPU) scaffolds, then implanted into the subcutaneous pockets on the back of nude mice. After 3 months of implantation, TEBGs based on dual micro-tissues performed larger volume of adipose tissue regeneration and neo-vessel formation compared to TEBGs based on single AMs. This study extends the application of micro-tissue engineering technique for the construction of soft grafts, and is expected to be useful for creating heterogeneous tissue constructs in the future.

Bleeding is an effective method to improve the starting performance of the inlet, and the conventional method often adopts the bleeding to longitudinal direction. This article proposes the use of transversal bleeding method to explore the influence on starting capacity by changing the bleeding direction. The paper designs 6 bleeding inlets. By calculating the starting performance, it is found that the projected bleeding rate of the inlet, which is the direct factor influencing the starting performance, would change due to the direction change of bleeding, although designed with the same entrance. For the inlet designed with longitudinal slots and bleeding, it could reach the starting state at Mach 3.6, but it showed the unstart state when they are transversal direction. The same entrance, when inlet is designed by transversal bleeding with longitudinal slots, the starting Mach number would decrease to 3.8. For the changes of aerodynamic capabilities, there would be the “point jump” tendency when reaching starting state, but the same inlets would keep the similar performance when they get the starting state.

Abstract Background Isocitrate dehydrogenase-2 (IDH2) is a mitochondrial enzyme that catalyzes the metabolic conversion between isocitrate and alpha-ketoglutarate (α-KG) in the TCA cycle. IDH2 mutation is an oncogenic event in acute myeloid leukemia (AML) due to the generation of 2-hydroxyglutarate. However, the role of wild-type IDH2 in AML remains unknown, despite patients with it suffer worse clinical outcome than those harboring mutant type. Methods IDH2 expression in AML cell lines and patient samples was evaluated by RT-qPCR, western blotting and database analyses. The role of wild-type IDH2 in AML cell survival and proliferation was tested using genetic knockdown and pharmacological inhibition in AML cells and animal models. LC–MS, GC–MS, isotope metabolic tracing, and molecular analyses were performed to reveal the underlying mechanisms. Results We found that wild-type IDH2 was overexpressed in AML and played a major role in promoting leukemia cell survival and proliferation in vitro and in vivo. Metabolomic analyses revealed an active IDH2-mediated reductive TCA cycle that promoted the conversion of α-KG to isocitrate/citrate to facilitate glutamine utilization for lipid synthesis in AML cells. Suppression of wild-type IDH2 by shRNA resulted in elevated α-KG and decreased isocitrate/citrate, leading to reduced lipid synthesis, a significant decrease in c-Myc downregulated by α-KG, and an inhibition of AML viability and proliferation. Importantly, pharmacological inhibition of IDH2 showed significant therapeutic effect in mice inoculated with AML cells with wt-IDH2 and induced a downregulation of C-MYC in vivo. Conclusions Wt-IDH2 is an essential molecule for AML cell survival and proliferation by promoting conversion of α-KG to isocitrate for lipid synthesis and by upregulating c-Myc expression and could be a potential therapeutic target in AML.

With an increase in rocket motor thrust, the thermal loads on the launch platform by the impingement exhaust jet are significantly increased, this poses serious safety risks to rocket launch. Therefore, a water cooling system should be designed to improve the thermal environment. In this study, the cooling effects of a water spray system with different injection velocities were analyzed through numerical simulation of high precision, and the afterburning effect of the exhaust gas was also considered to improve the calculation accuracy. The results showed that afterburning primarily occurred in the mixing layer, leading to a larger high-temperature region in the impingement plate. The water cooling system realized thermal protection for the launch platform, which was achieved by decreasing the temperature and velocity of impingement jet. With an increase in the aqueous jet velocity, a more significant cooling effect of the water spray system was obtained. However, the guiding performance of the deflector was decreased owing to the large amount of water vapor formed in the channel. It is suggested that the water spray system design should adopt an aqueous jet velocity of 20 m/s as a parameter after considering the cooling effect and guiding performance of the deflector.