Because the selective laser melting (SLM) formation process involves rapid melting and solidification of slices, the SLM process places high demands on the tightness, uniformity, and flatness of the ...powder layer. Based on the discrete element method (particle contact force model, particle collision judgment algorithm, and particle motion equation) and the SLM laying powder process, a numerical simulation of the SLM laying powder process was carried out. For the performance measurement experiment of the TC4 titanium alloy powder, the powder bulk density, tap density, and angle of repose were calculated and analyzed. It was found that the tap density increased by 7.5% compared to the bulk density, and the calculated average angle of repose (32.6°) was in good agreement with the experimental data (33.2°), thus verifying the accuracy of the calculation model used for the SLM laying powder. The influences of different scraping methods and scraping speeds on the quality of the laying powder were calculated and analyzed. It was found that the scraping method using a roller (not rotating) obtained the highest tightness and most uniform powder distribution, and, as the scraping speed increased, the laying tightness tended to decrease linearly. The results of the numerical simulation study of the SLM laying powder process can be used to guide the actual SLM laying powder process and, alternatively, provide basic data for the numerical simulation of SLM molten pool dynamics based on the particle scale.
During the COVID-19 pandemic, many universities are confronted with campus lockdown or even school closures to reduce the risk of infection. However, these measures pose a threat to the mental health ...of adolescents. In particular, freshmen who have just entered the university campus may suffer from more serious mental health risks. In this study, 1,818 freshmen were analyzed by using the Chinese College Student Adjustment Scale (CCSAS), Sense of Security Questionnaire (SQ), and Symptom Check List 90 (SCL-90) of the qualitative method. The results showed that adjustment had an impact on mental health. Firstly, there was a significant negative association between adjustment and mental health. Secondly, adjustment had a significant predictive effect on mental health. Finally, a sense of security and gender affected the relationship between adjustment and mental health. Collectively, adjustment, sense of security, and gender exerted impacts on the mental health of freshmen, suggesting that we should create a warm and harmonious campus environment for students and conduct targeted education for male and female students.
Circulating in China and 158 other countries and areas, the ongoing COVID-19 outbreak has caused devastating mortality and posed a great threat to public health. However, efforts to identify ...effectively supportive therapeutic drugs and treatments has been hampered by our limited understanding of host immune response for this fatal disease. To characterize the transcriptional signatures of host inflammatory response to SARS-CoV-2 (HCoV-19) infection, we carried out transcriptome sequencing of the RNAs isolated from the bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cells (PBMC) specimens of COVID-19 patients. Our results reveal distinct host inflammatory cytokine profiles to SARS-CoV-2 infection in patients, and highlight the association between COVID-19 pathogenesis and excessive cytokine release such as CCL2/MCP-1, CXCL10/IP-10, CCL3/MIP-1A, and CCL4/MIP1B. Furthermore, SARS-CoV-2 induced activation of apoptosis and P53 signalling pathway in lymphocytes may be the cause of patients' lymphopenia. The transcriptome dataset of COVID-19 patients would be a valuable resource for clinical guidance on anti-inflammatory medication and understanding the molecular mechansims of host response.
Nickel-based superalloys are one of the most industrially important families of metallic alloys at present. Selective Laser Melting (SLM), as one of the additive manufacturing technologies for ...directly forming complex metal parts, has been applied in the production of Inconel 718 components. Based on the more reasonable and comprehensive equivalent processing models (vaporization heat loss, equivalent physical parameters) for the nickel-based superalloy SLM process, an SLM molten pool dynamic behavior prediction model on the workpiece scale was established. Related equivalent processing models were customized by secondary development with the software Fluent. In order to verify the feasibility of the SLM molten pool dynamics model, the SLM single-pass employed to form the Inconel 718 alloy process was calculated. The simulated and experimental solidified track dimensions were in good agreement. Then, the influences of different process parameters (laser power, scanning speed) on the SLM formation of the Inconel 718 alloy were calculated and analyzed. The simulation and experimental solidified track widths were well-matched, and the result showed that, as a rule, the solidified track width increased linearly with the laser power and decreased linearly with the scanning speed. This paper will help lay the foundation for a subsequent numerical simulation study of the thermal-melt-stress evolution process of an SLM workpiece.
Summary
Blood–brain barrier (BBB) dysfunction is considered to be an early event in the pathogenesis of a variety of neurological diseases in old patients, and this could occur in old people even ...when facing common stress. However, the mechanism remains to be defined. In this study, we tested the hypothesis that decreased melatonin levels may account for the BBB disruption in old mice challenged with lipopolysaccharide (LPS), which mimicked the common stress of sepsis. Mice (24–28 months of age) received melatonin (10 mg kg−1 day−1, intraperitoneally, i.p.) or saline for one week before exposing to LPS (1 mg kg−1, i.p.). Evan's blue dye (EB) and immunoglobulin G (IgG) leakage were used to assess BBB permeability. Immunostaining and Western blot were used to detect protein expression and distribution. Our results showed that LPS significantly increased BBB permeability in old mice accompanied by the degradation of tight junction proteins occludin and claudin‐5, suppressed AMP‐activated protein kinase (AMPK) activation, and elevated gp91phox protein expression. Interestingly, administration of melatonin for one week significantly decreased LPS‐induced BBB disruption, AMPK suppression, and gp91phox upregualtion. Moreover, activation of AMPK with metformin significantly inhibited LPS‐induced gp91phox upregualtion in endothelial cells. Taken together, our findings demonstrate that melatonin alleviates LPS‐induced BBB disruption through activating AMPK and inhibiting gp91phox upregulation in old mice.
DNA methylation regulates many cellular processes, including embryonic development, transcription, chromatin structure, X-chromosome inactivation, genomic imprinting and chromosome stability. DNA ...methyltransferases establish and maintain the presence of 5-methylcytosine (5mC), and ten-eleven translocation cytosine dioxygenases (TETs) oxidise 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), which can be removed by base excision repair (BER) proteins. Multiple forms of DNA methylation are recognised by methyl-CpG binding proteins (MeCPs), which play vital roles in chromatin-based transcriptional regulation, DNA repair and replication. Accordingly, defects in DNA methylation and its mediators may cause silencing of tumour suppressor genes and misregulation of multiple cell cycles, DNA repair and chromosome stability genes, and hence contribute to genome instability in various human diseases, including cancer. Thus, understanding functional genetic mutations and aberrant expression of these DNA methylation mediators is critical to deciphering the crosstalk between concurrent genetic and epigenetic alterations in specific cancer types and to the development of new therapeutic strategies.
Late Cretaceous magmatism has been widely documented in the Great South Basin (GSB) of New Zealand, which is mainly relevant to the Gondwana break-up (105–83 Ma) and the separation of Zealandia from ...Australia and Antarctica (83–66 Ma). However, the magma plumbing system in the GSB is still poorly understood. In this study, we used a high-resolution 3D seismic reflection data to investigate the igneous intrusions that developed in the northern part of GSB. These igneous intrusions occurred from ∼75 Ma to ∼58 Ma that corresponded to the spreading of the Tasman Sea and the Southern Ocean. Most of the igneous intrusions developed above listric faults which formed during rifting stage. Moreover, dykes are also observed between the listric faults and igneous intrusions. Listric faults, dykes and sills formed the magma plumbing system of GSB. This study explored the possible origin of post-rift magmatism in the GSB, and addressed the post-rift magma plumbing system in detail, which greatly promoted the understanding of GSB’ evolution, resource exploration and marine geological hazard assessment.
•Magma plumbing system of the Great South Basin is described for the first time.•Magmatic activity during the Late Cretaceous is related to the spreading of the Tasman Sea and the Southern Ocean.•The distribution of igneous intrusions in the Great South Basin is controlled by the listric faults.
Opioids, such as morphine, are clinic analgesics which induce euphoria. Morphine exposure modifies the excitability and functional interactions between neurons, while the underlying cellular and ...molecular mechanisms, especially how morphine assembles heterogeneous interneurons (INs) in prelimbic cortex (PrL) to mediate disinhibition and reward, are not clear. Using approaches of optogenetics, electrophysiology, and cell type-specific RNA-seq, we show that morphine attenuates the inhibitory synaptic transmission from parvalbumin
(PV)-INs onto pyramidal neurons in PrL via μ-opioid receptor (MOR) in PV-INs. Meanwhile, morphine enhances the inhibitory inputs from somatostatin
(SST)-INs onto PV-INs, and thus disinhibits pyramidal neurons via δ-opioid receptor (DOR)-dependent Rac1 upregulation in SST-INs. We show that MOR in PV-INs is required for morphine-induced behavioral sensitization, while DOR as well as Rac1 activity in SST-INs is required for morphine-induced conditioned place preference and hyper-locomotion. These results reveal that SST- and PV-INs, functioning in PrL as a disinhibitory architecture, are coordinated by morphine via different opioid receptors to disinhibit pyramidal neurons and enhance reward.
Natural products have traditionally been rich sources for drug discovery. In order to clear the road toward the discovery of unknown natural products, biologists need dereplication strategies that ...identify known ones. Here we report DEREPLICATOR+, an algorithm that improves on the previous approaches for identifying peptidic natural products, and extends them for identification of polyketides, terpenes, benzenoids, alkaloids, flavonoids, and other classes of natural products. We show that DEREPLICATOR+ can search all spectra in the recently launched Global Natural Products Social molecular network and identify an order of magnitude more natural products than previous dereplication efforts. We further demonstrate that DEREPLICATOR+ enables cross-validation of genome-mining and peptidogenomics/glycogenomics results.
Due to the complex composition and similar structure, the extraction denitrification of aromatic rich oil is faced with the contradiction problem of denitrification efficiency and aromatic loss which ...cannot be efficiently solved by experiments. However, the complex interactions involved can be analyzed from the perspective of calculation, and the prediction criteria and methods are proposed. Based on rigorous density functional theory calculation data, Simple models based on electrostatic potential (ESP) and Van der Waals potential (VdWP)‐based calculations were established and validated. The twofold model provided the best prediction for interactions between extractants and nitrogen compounds and between extractants and aromatics, which determines denitrification efficiency and aromatic loss, respectively, due to the most complete description of both electrostatic and VdW force. This provides a powerful tool for evaluating the non‐covalent interactions and thence tuning the efficiency of the separation process. Thus, high denitrification efficiency (43.2~66.3 %) and moderate aromatic loss (1.7~4.4 %) were obtained using screened deep eutectic solvents (DESs). This ideal observation provided the potential for mild hydrodesulfurization and manufacture of high‐grade carbon materials.
To resolve the contradiction between denitrification efficiency and polycyclic aromatic hydrocarbon (PAH) loss due to complex interactions, a combined model is proposed to evaluate the extraction performance in experiments. It is essential for the preparation of low nitrogen feedstock for a wide range of carbon materials.
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