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Naphthoquinone (1,4-NQ) and its derivatives (NQs, juglone, plumbagin, 2-methoxy-1,4-NQ, and menadione) have a variety of therapeutic applications, many of which are attributed to redox cycling and the production of reactive oxygen species (ROS). We previously demonstrated that NQs also oxidize hydrogen sulfide (H2S) to reactive sulfur species (RSS), potentially conveying identical benefits. Here we use RSS-specific fluorophores, mass spectroscopy, EPR and UV-Vis spectrometry, and oxygen-sensitive optodes to examine the effects of thiols and thiol-NQ adducts on H2S-NQ reactions. In the presence of glutathione (GSH) and cysteine (Cys), 1,4-NQ oxidizes H2S to both inorganic and organic hydroper-/hydropolysulfides (R2Sn, R=H, Cys, GSH; n = 2–4) and organic sulfoxides (GSnOH, n = 1, 2). These reactions reduce NQs and consume oxygen via a semiquinone intermediate. NQs are also reduced as they form adducts with GSH, Cys, protein thiols, and amines. Thiol, but not amine, adducts may increase or decrease H2S oxidation in reactions that are both NQ- and thiol-specific. Amine adducts also inhibit the formation of thiol adducts. These results suggest that NQs may react with endogenous thiols, including GSH, Cys, and protein Cys, and that these adducts may affect both thiol reactions as well as RSS production from H2S.

Green design and manufacturing strategies are necessary to cope with the current resource, energy, and environmental problems of the manufacturing industry. To meet various enterprises’ needs for green design and manufacturing, colleges and universities should integrate these concepts into their curricula. This study discusses the application of green strategies in the mechanical engineering field from the viewpoints of teaching, scientific research, and practical education. Based on its development and a basic connotation analysis, this study highlights the challenges and urgency of incorporating green concepts into teaching and research modules of mechanical engineering, as well as methods and implementation strategies to incorporate them in professional curricula using teaching method reform and the teaching and research integration method. An experimental training course of advanced manufacturing processes at the authors’ institution was amended to emphasize the integrated application of green design and manufacturing. This integration not only enriches the field of mechanical engineering but also provides scientific research directions and methods to educators, along with new ideas to imbibe students with mechanical talents for their technical development. These efforts lay the foundation for the sustainable development of China’s manufacturing industry.

With growing concerns about energy and environmental issues, much research attention has been focused on manufacturing activities that consume significant amounts of energy and influence the environment. In the manufacturing field, additive manufacturing (AM) is a new production technology that can process complex parts and has high material utilization, which also has the problem of excessive energy consumption and has raised concern. However, the existing research primarily focuses on the process of AM energy consumption and its impact on the environment; the energy consumption distribution of AM equipment is still lacking. This study proposes an analytical method for addressing the energy consumption distribution of AM equipment by classifying the equipment into different energy units. In particular, the energy consumption and energy distribution of different types of AM equipment including fused deposition modeling (FDM), stereo lithography apparatus, and selective laser melting are discussed. Then, the energy consumption distribution characteristics of the three different AM equipment are investigated by machining a conventional structure using the proposed energy consumption quantification method based on energy units. The results show that the proposed method can effectively and quickly predict the energy consumption of AM equipment. Based on the energy consumption distribution method, to improve the process energy efficiency, a process optimization method considering energy consumption and forming quality is proposed to obtain the optimal process parameters of FDM. This method can provide support for energy consumption prediction and energy efficiency improvement of AM.

Additive manufacturing (AM) is a novel manufacturing technology that can create highly customized products with more complex geometries than traditional techniques. Despite its significant advantages, including the freedom of design, mass customization, and ability to produce complex structures, AM consumes a large amount of energy and incurs high costs. In addition, AM suffers from long production cycles and low production efficiency in the large-scale manufacturing of metal structures. This study offers a review of the existing literature focused on metal AM technology. To avoid the shortcomings of AM and highlight its benefits, which are widely used for manufacturing in combination with casting. The current combination application of AM and casting is reviewed to provide solutions to the problem of manufacturing large metal components from the perspective of the use of different AM technology and quality control in casting. However, such integration is insufficient for producing large castings with complex shapes, structures, or multiple features. Therefore, a novel method for integrating AM into casting to enable the manufacture of large scale metal parts with complex shapes is introduced as a topic for possible future research. This method divides complex castings with multiple features into an AM processing part and the casting substrate. The complex features were processed by AM on the fabricated casting substrate. This study provides a review of the application of AM into casting and presents a novel idea for the integration application of AM and other processes. This promising method has significant value for future study.

1,4-Napththoquinones (NQs) are clinically relevant therapeutics that affect cell function through production of reactive oxygen species (ROS) and formation of adducts with regulatory protein thiols. Reactive sulfur species (RSS) are chemically and biologically similar to ROS and here we examine RSS production by NQ oxidation of hydrogen sulfide (H

In order to guide the management, protection and utilization of wetlands in Shaanxi Province, this paper analyzes and summarizes the current situation and existing problems of the protection and utilization of wetland resources in Shaanxi Province, and puts forward suggestions accordingly. There are 4 wetlands and 12 wetland types in Shaanxi Province, 308,500 hectares. The area and proportion of various wetlands are 257,600 hectares of river wetlands, 83.50%; 32,300 hectares of artificial wetlands, 10.46%; 7,600 hectares of lake wetlands, 2.46%; and 11,000 hectares of swamp wetlands, 3.58%. There are 77 families, 207 genera, 341 species and 3 varieties of wild vascular plants in the wetland, including 2 species of key wild protected species at the national level and 4 species at the provincial level. In view of the problems in the protection and utilization, such as the collaborative mechanism has not been established, the resource background has not been completely clear, and the investment is insufficient, we should build a scientific and appropriate wetland evaluation index system in Shaanxi Province, carry out the investigation and evaluation of wetland resources in the province, continue to carry out wetland ecological restoration and reconstruction projects, establish and improve wetland protection management and technical system, and formulate the protection and utilization direction of different types of wetlands.

Cyclooxygenase (COX)-dependent production of prostaglandins (PGs) is known to play important roles in tumorigenesis. PGD2 has recently emerged as a key regulator of tumor- and inflammation-associated functions. Here we show that mesenchymal stromal cells (MSCs) from patients with acute myeloid leukemia (AML) or normal MSCs overexpressing COX2 promote proliferation of co-cultured hematopoietic stem and progenitor cells (HSPCs), which can be prevented by treatment with COX2 knockdown or TM30089, a specific antagonist of the PGD2 receptor CRTH2. Mechanistically, we demonstrate that PGD2-CRTH2 signaling acts directly on type 2 innate lymphoid cells (ILC2s), potentiating their expansion and driving them to produce Interleukin-5 (IL-5) and IL-13. Furthermore, IL-5 but not IL-13 expands CD4+CD25+IL5Rα+ T regulatory cells (Tregs) and promotes HSPC proliferation. Disruption of the PGD2-activated ILC2-Treg axis by specifically blocking the PGD2 receptor CRTH2 or IL-5 impedes proliferation of normal and malignant HSPCs. Conversely, co-transfer of CD4+CD25+IL5Rα+ Tregs promotes malignant HSPC proliferation and accelerates leukemia development in xenotransplanted mice. Collectively, these results indicate that the mesenchymal source of PGD2 promotes proliferation of normal and malignant HSPCs through activation of the ILC2-Treg axis. These findings also suggest that this novel PGD2-activated ILC2-Treg axis may be a valuable therapeutic target for cancer and inflammation-associated diseases.

In the canonical pathway for mitochondrial H

1,4-Napththoquinones (NQs) are clinically relevant therapeutics that affect cell function through production of reactive oxygen species (ROS) and formation of adducts with regulatory protein thiols. Reactive sulfur species (RSS) are chemically and biologically similar to ROS and here we examine RSS production by NQ oxidation of hydrogen sulfide (H2S) using RSS-specific fluorophores, liquid chromatography-mass spectrometry, UV-Vis absorption spectrometry, oxygen-sensitive optodes, thiosulfate-specific nanoparticles, HPLC-monobromobimane derivatization, and ion chromatographic assays. We show that NQs, catalytically oxidize H2S to per- and polysulfides (H2Sn, n = 2–6), thiosulfate, sulfite and sulfate in reactions that consume oxygen and are accelerated by superoxide dismutase (SOD) and inhibited by catalase. The approximate efficacy of NQs (in decreasing order) is, 1,4-NQ ≈ juglone ≈ plumbagin > 2-methoxy-1,4-NQ ≈ menadione >> phylloquinone ≈ anthraquinone ≈ menaquinone ≈ lawsone. We propose that the most probable reactions are an initial two-electron oxidation of H2S to S0 and reduction of NQ to NQH2. S0 may react with H2S or elongate H2Sn in variety of reactions. Reoxidation of NQH2 likely involves a semiquinone radical (NQ·−) intermediate via several mechanisms involving oxygen and comproportionation to produce NQ and superoxide. Dismutation of the latter forms hydrogen peroxide which then further oxidizes RSS to sulfoxides. These findings provide the chemical background for novel sulfur-based approaches to naphthoquinone-directed therapies.

Objective: To compare the clinical efficacy, safety, and prognosis of full-threaded headless cannulated compression screws (HCCSs) and anatomical plates (APs) in the treatment of triplane fractures of the distal tibia. Methods: In this retrospective study, 74 patients with triplane fractures of the distal tibia treated in our hospital from April 2017 to March 2019 were selected as the research subjects. Among them, 38 patients receiving full-threaded HCCSs were assigned to the research group (RG), and the remaining 36 patients receiving APs were assigned to the control group (CG). The general indices, including operation, fracture healing, and ambulation times, efficacy, and complications were recorded and compared between the two groups. Visual analogue scale (VAS) was applied to assess pain, and a quality of life (QOL) survey was conducted at 6 months after surgery. Results: Compared with the CG, the operation time, fracture healing time, and ambulation time of the RG were significantly shortened (P

Additive manufacturing (AM) technologies, such as direct laser and selective laser melting (SLM) manufacturing, allow the fabrication of functional products with high added value. This paper proposes an emergy-based method for evaluating the environmental impact and economic cost of the SLM manufacturing process while considering the environmental flows (materials, energy, and wastes) and economic factors (time, costs, and quality). By analyzing the emergy flows in an SLM system, sustainable evaluation indexes are developed to estimate its sustainability level. Then, the method is applied to analyze the environmental impact and economic cost of the SLM of a part. The results show that the cost of the process for a single part is high, the net emergy yield ratio of the SLM system is low, and its environmental load rate is very high. The sustainability indexes of the system indicated a high environmental impact and low production efficiency. However, the waste emergy output ratio of the system was very low, which reflected the near-net-shape characteristics of SLM, indicating a high sustainability potential. The results of this study are expected to contribute to increased sustainability and optimization of SLM.

Additive manufacturing (AM) has significant advantages over conventional manufacturing technologies, including freedom of design, mass customization, and the ability to produce complex structures. Because reducing manufacturing energy is an essential challenge for industrial sustainability and national economics, the trend toward AM motivates us to explore the energy consumption of AM to address energy efficiency. Existing energy consumption quantitation methods for AM parts require complex models, and the energy consumption characteristics of AM equipment muse be considered in the quantitative analysis process. Therefore, a feature-based energy consumption quantitation method for complex AM parts is proposed that uses a simple model and can be applied to different AM technologies. A feature segmentation method is first proposed to divide complex AM parts into typical AM features (AMFs). Then, the energy consumption model is developed for each AMF to quantify the energy consumption during fabrication of the entire part. Finally, the energy consumption characteristics of a typical mechanical part manufactured by three different kinds of AM processes—fuse deposition modeling (FDM), stereolithography (SLA), and selective laser melting (SLM)—are investigated using the proposed feature-based energy consumption quantitation method and measured in an experimental case study. The results show that the proposed method can effectively and quickly predict the energy consumption of AM part manufacturing. Moreover, the efficiency of different types of AM processes is compared and discussed to address applicable efficiency improvement methods. This method can predict the energy consumption of complex AM parts, and can be integrated into the AM three-dimensional software model, providing a reference for structural optimization of AM parts.

The transcriptional repressor Hairy Enhancer of Split 1 (HES1) plays an essential role in the development of many organs by promoting the maintenance of stem/progenitor cells, controlling the reversibility of cellular quiescence, and regulating both cell fate decisions. Deletion of Hes1 in mice results in severe defects in multiple organs and is lethal in late embryogenesis. Here we have investigated the role of HES1 in hematopoiesis using a hematopoietic lineage-specific Hes1 knockout mouse model. We found that while Hes1 is dispensable for steady-state hematopoiesis, Hes1-deficient hematopoietic stem cells (HSCs) undergo exhaustion under replicative stress. Loss of Hes1 upregulates the expression of genes involved in PPARγ signaling and fatty acid metabolism pathways, and augments fatty acid oxidation (FAO) in Hes1f/fVav1Cre HSCs and progenitors. Functionally, PPARγ targeting or FAO inhibition ameliorates the repopulating defects of Hes1f/fVav1Cre HSCs through improving quiescence in HSCs. Lastly, transcriptome analysis reveals that disruption of Hes1 in hematopoietic lineage alters expression of genes critical to HSC function, PPARγ signaling, and fatty acid metabolism. Together, our findings identify a novel role of HES1 in regulating stress hematopoiesis and provide mechanistic insight into the function of HES1 in HSC maintenance.

Reducing the mass of vehicles is an effective way to improve energy efficiency and mileage. Therefore, hot stamping is developed to manufacture lightweight materials used for vehicle production, such as magnesium and aluminum alloys. However, in comparison with traditional cold stamping, hot stamping is a high-energy-consumption process, because it requires heating sheet materials to a certain temperature before forming. Moreover, the process parameters of hot stamping considerably influence the product forming quality and energy consumption. In this work, the energy-economizing indices of hot stamping are established with multiobjective consideration of energy consumption and product forming quality to find a pathway by which to obtain optimal hot stamping process parameters. An energy consumption index is quantified by the developed models, and forming quality indices are calculated using a finite element model. Response surface models between the process parameters and energy-economizing indices are established by combining the Latin hypercube design and response surface methodology. The multiobjective problem is solved using a multiobjective genetic algorithm (NSGA-II) to obtain the Pareto frontier. ZK60 magnesium alloy hot stamping is applied as a case study to obtain an optimal combination of parameters, and compromise solutions are compared through stamping trials and numerical simulations. The obtained results may be used for guiding process optimization regarding energy saving and the method of manufacturing parameters selection.

NOD-like receptor 12 (NLRP12) is a member of the nucleotide-binding domain and leucine-rich repeat containing receptor inflammasome family that plays a central role in innate immunity. We previously showed that DNA damage upregulated NLRP12 in hematopoietic stem cells (HSCs) of mice deficient in the DNA repair gene Fanca. However, the role of NLRP12 in HSC maintenance is not known. Here, we show that persistent DNA damage–induced NLRP12 improves HSC function in both mouse and human models of DNA repair deficiency and aging. Specifically, treatment of Fanca(–/–) mice with the DNA cross-linker mitomycin C or ionizing radiation induces NLRP12 upregulation in phenotypic HSCs. NLRP12 expression is specifically induced by persistent DNA damage. Functionally, knockdown of NLRP12 exacerbates the repopulation defect of Fanca(–/–) HSCs. Persistent DNA damage–induced NLRP12 was also observed in the HSCs from aged mice, and depletion of NLRP12 in these aged HSCs compromised their self-renewal and hematopoietic recovery. Consistently, overexpression of NLRP12 substantially improved the long-term repopulating function of Fanca(–/–) and aged HSCs. Finally, persistent DNA damage–induced NLRP12 maintains the function of HSCs from patients with FA or aged donors. These results reveal a potentially novel role of NLRP12 in HSC maintenance and suggest that NLRP12 targeting has therapeutic potential in DNA repair disorders and aging.

The runoff amount, soil erosion amount and infiltration rate were analyzed on different rainfall and different underlying horizon in base of yellow river institute of hydraulic research at 2018. The date shows: the runoff amount of bare slope is 7 times that of grass slope, the runoff amount of heavy rainfall is 2 times that of middle rainfall and is 20 times that of small rainfall; the soil erosion amount of bare slope and arable slope is 100 times that of grass slope; the steady soil erosion amount of small rainfall is 1/4 times that of middle rainfall and is 1/30 times that of heavy rainfall on grass slope; the infiltration rate of bare slope and arable slope is 1/3 times of grass slope; the grass slope infiltration rate is about 0.6mm/min in small rainfall, the middle and heavy rainfall get the steady infiltration rate at experiment continue 30min and 12min.

Cyclooxygenase (COX)-dependent production of prostaglandins (PGs) is known to play important roles in tumorigenesis. PGD2 has recently emerged as a key regulator of tumor- and inflammation-associated functions. We previously reported that mesenchymal stromal cells (MSCs) from patients with acute myeloid leukemia (AML) overexpressed COX-2 and secreted high levels of PGs including PGD2. Since little is known about the role of PGD2 in normal and malignant hematopoiesis, we prioritized this mesenchymal source of PG for further investigation. We observed that AML MSCs or normal MSCs overexpressing COX-2 promotes proliferation of co-cultured hematopoietic stem and progenitor cells (HSPCs), which can be prevented by treatment with COX-2 knockdown or TM30089, a specific antagonist of the PGD2 receptor CRTH2. Mechanistically, we demonstrate that PGD2-CRTH2 signaling acts directly on type 2 innate lymphoid cells (ILC2s), potentiating their expansion and driving them to produce Interleukin-5 (IL-5) and IL-13. We further show that IL-5 but not IL-13 expands CD25+Foxp3+ IL5Ra+ T regulatory cells (Tregs) and promotes HSCP proliferation. Disruption of the PGD2-activated ILC2-Treg axis by specifically blocking the PGD2 receptor CRTH2 or IL-5 impedes proliferation of normal and malignant HSPCs. Conversely, co-transfer of Lin-CD127+CRTH2+ ILC2s and CD4+CD25+IL5Ra+ Tregs promotes malignant HSCP proliferation and accelerates leukemia development in xenotransplanted mice. Collectively, these results indicate that the mesenchymal source of PGD2 promotes proliferation of normal and malignant HSPCs through activation of the ILC2-Treg axis. These findings also suggest that this PGD2-activated ILC2-Treg axis may be a valuable therapeutic target for cancer and inflammation-associated diseases. Disclosures No relevant conflicts of interest to declare.

The rainfall feature were analyzed at Yinchuan city in this paper, the rainfall feature was detected by LPM laser raindrop spectrometer, including rainfall raindrops speed and raindrops size. The data shows that the rainfall raindrops speed and size of natural raindrops were relatively strongly; In the process of individual rainfall, the rainfall raindrops final speed of the rain is mainly distribution between 0.6-5.8m/s, the biggest of the final speed is generally 1.0m/s; and rainfall raindrops is mainly composed of the particle size of 0.125- 0.5mm rainfall raindrops. The rainfall raindrops speed of 0.125mm diameter is mainly distribute between 0.6-1.8m/s, the rainfall raindrops speed of 0.25mm particle size is mainly distribute between 0.8-1.8m/s, the rainfall raindrops speed of 0.375mm distribute in the 1-1.8m/s, the rainfall raindrops speed of 0.5mm particle size of the raindrops mainly distribute in the 1.0-2.2m/s.

In our previous study, Rhizoma Coptidis extract was found to exert more potent inhibitory effect than its major component berberine towards urease from Helicobacter pylori (HPU) and jack bean (JBU). In continuation of our work, the present study was designed to further comparatively investigate the urease inhibitory activities of five major protoberberine alkaloids in Rhizoma Coptidis, namely berberine, palmatine, coptisine, epiberberine, jateorhizine to identify the bioactive constituent, and illuminate the potential mechanism of action. Results indicated that the five protoberberine alkaloids acted as concentration-dependent inactivators of urease with IC50 values ranging between 3.0 and 5087μM for HPU and 2.3->10,000μM for JBU, respectively. Notably, epiberberine (EB) was found to be the most potent inhibitor against both ureases with IC50 values of 3.0±0.01μM for HPU and 2.3±0.01μM for JBU, which was more effective than the standard urease inhibitor, acetohydroxamic acid (83±0.01μM for HPU and 22±0.01μM for JBU, respectively). Further kinetic analysis revealed that the type of EB inhibition against HPU was slow-binding and uncompetitive, with Ki of 10.6±0.01μM, while slow-binding and competitive against JBU with Ki of 4.6±0.01μM. Addition of thiol reagents, such as l-cysteine, glutathione and dithiothreitol, significantly abolished the inhibition, while Ni2+ competitive inhibitors, boric acid and sodium fluoride, synergetically inhibited urease with EB, indicating the obligatory role of the active site sulfhydryl group for the inhibition. In addition, binding of EB with the urease proved to be reversible, as about 65% and 90% enzymatic activity of HPU and JBU, respectively, could be restored by dithiothreitol application. These findings highlighted the potential role of Rhizoma Coptidis protoberberine alkaloids, especially EB, as a lead urease inhibitor in the treatment of diseases associated with ureolytic bacteria. Thus, EB had good potential for further development into a promising therapeutic approach for the treatment of urease-related diseases.

In this study, a new functionalized peptide RLN was designed containing the bioactive motif link N, the amino terminal peptide of link protein. A link N nanofiber scaffold (LN-NS) was self-assembled by mixing peptide solution of RLN and RADA16. The characterization of LN-NS was tested using atomic force microscopy (AFM). The biocompatibility and bioactivity of this nanofiber scaffold for rabbit nucleus pulposus cells (NPCs) were also evaluated. This designer functionalized nanofiber scaffold exhibited little cytotoxicity and promoted NPCs adhesion obviously. In three-dimensional cell culture experiments, confocal reconstructed images testified that the functionalized LN-NS-guided NPCs migration from the surface into the hydrogel considerably, in which the RADA16 scaffold did not. Moreover, the functionalized LN-NS significantly stimulated the biosynthesis of extracelluar matrices (ECM) by NPCs. Our findings demonstrate that the functionalized nanofiber scaffold containing link N had excellent biocompatibility and bioactivity with rabbit NPCs and could be useful in the nucleus pulposus regeneration.

To evaluate the clinical outcomes of two different surgical treatments for arachnoid cysts in sacral canal.From January 2004 to March 2009, 55 cases of arachnoid cysts in the sacral canal were treated by traditional simple sacral laminectomies with resection of the cysts (group A, 25 cases) and novel CT-guided percutaneous fibrin glue therapy of arachnoid cysts (group B, 30 cases). Of them, there were 23 males and 32 females, aging 15-66 years with an average of 42.6 years; the duration of symptoms was 6 months to 15 years with an average of 3.5 years. L5-S1 was involved in 22 cases, S1,2 in 25 cases, S2,3 in 12 cases, S2 in 8 cases, and presacral in 2 cases. The size of cysts was 1.5 cm x 1.0 cm to 6.0 cm x 2.8 cm. The MRI examination showed that all patients had cysts in the sacral canal. There were no significant difference (P0.05) in sex, ages, disease duration and cysts size between two groups. Preoperative data and postoperative lumbosacral pain and function improvement were analyzed and compared between two groups.All operations were performed successfully. The operative time, blood loss and hospitalization days of group B were significantly less than those of group A (P0.01). All 55 cases were followed up from 9 to 61 months (mean 23 months). In group A, postoperative cerebrospinal fluid leakage (25 cases), intracranial infection (2 cases), nerve injury (3 cases), and nerve root irritation (8 cases) occurred; in group B, mild meningitis (3 cases) and low grade fever (5 cases) occurred. Except for nerve injury, other complications were cured after symptomatic management. During the follow-up, 2 recurrent cases were found in group A and 1 case in group B. Of them, 2 recurrent cases were treated with CT-guided percutaneous fibrin glue therapy of arachnoid cysts, and cysts disappeared. For two groups, there were significant differences in Oswestry functional disability index and visual analogue scale score between preoperation and postoperation (P0.01), and in the rate of score improvement between two groups (P0.01). According to the rating scale, the excellent and good rates of pain improvement were 64% in group A and 100% in group B; the excellent and good rates of function improvement were 24% in group A and 97% in group B.CT-guided percutaneous fibrin glue therapy for arachnoid cysts in the sacral canal is a mini-invasive, safe, effective, and economical method, it may be better choices for the treatment of arachnoid cysts in the sacral canal.