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Background: Zuotai (mainly β-HgS)-containing 70 Wei-Zhen-Zhu-Wan (70W, Rannasangpei) is a famous Tibetan medicine for treating cardiovascular and gastrointestinal diseases. We have shown that 70W protected against CCl 4 hepatotoxicity. CCl 4 is metabolized via cytochrome P450 (CYP) to produce reactive metabolites. Whether 70W has any effect on CYPs is unknown and such effects should be compared with mercury compounds for safety evaluation. Methods: Mice were given clinical doses of 70W (0.15-1.5 g/kg, po), Zuotai (30 mg/kg, po), and compared to HgCl 2 (33.6 mg/kg, po) and MeHg (3.1 mg/kg, po) for seven days. Liver RNA and protein were isolated for qPCR and Western-blot analysis. Results: 70W and Zuotai had no effects on hepatic mRNA expression of Cyp1a2, Cyp2b10, Cyp3a11, Cyp4a10 and Cyp7a1, and corresponding nuclear receptors [aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), pregnane X receptor (PXR), peroxisome proliferator-activated receptor-α (PPARα); farnesoid X receptor (FXR)]. In comparison, HgCl 2 and MeHg increased mRNA expression of Cyp1a2, Cyp2b10, Cyp4a10 and Cyp7a1 except for Cyp3a11, and corresponding nuclear receptors except for PXR. Western-blot confirmed mRNA results, showing increases in CYP1A2, CYP2B1, CYP2E1, CYP4A and CYP7A1 by HgCl 2 and MeHg only, and all treatments had no effects on CYP3A. Conclusions: Zuotai and Zuotai-containing 70W at clinical doses had minimal influence on hepatic CYPs and corresponding nuclear receptors, while HgCl 2 and MeHg produced significant effects. Thus, the use of total Hg content to evaluate the safety of HgS-containing 70W is inappropriate.

AIM: To report the data of 28 cases of congenital nasolacrimal duct obstruction who failed in the first probing of lacrimal passage in our hospital, summarize the strategy of retreatment. METHODS: Retrospective study, selected 591 cases of children with 28 cases in our hospital from Feb. 1, 2013 to Dec. 31, 2017, all were for the first time of probing of lacrimal passage through failure of children with congenital nasolacrimal duct obstruction(not including traumatic and lacrimal duct abnormalities), collect the case history, the nasal situation, the age of the first time to probing of lacrimal passages, information such as case data before and after treatment.RESULTS:In 28 cases, 15 cases with probing of lacrimal passage joint tube insertion second time, take the tube after cured, 10 cases treated with inferior turbinate, again with probing of lacrimal passage joint tube insertion, take the tube after cured, 2 cases of children with acute dacryocystitis often strikes, under general anesthesia with transnasal endoscopic dacryocystorhinostomy, 1 cases of children with bony nasolacrimal duct obstruction and strictures, with tears spill without overflow pus, pay a follow-up visit, sinus fully developed after the age of 13 under transnasal endoscopic dacryocystorhinostomy.CONCLUSION: Congenital nasolacrimal duct obstruction of lacrimal duct exploration for the first time failed again take personalized ladder solution treatment, reasonable treatment of the disease.

The oil film lubrication performance of a large hydrostatic turntable operating at the model of constant surface cutting speed is studied. Firstly, the rotary speed equation which is bound by the constant surface cutting speed is established. According to the fluid lubrication theory, the gap flow equation, the oil film temperature rise equation and the double‐rectangular‐cavity oil pad bearing capacity equation are derived. Further, a prediction model of oil film lubrication performance in the operating mode is established. The change rules of temperature, pressure and other performance indexes of the film with time are obtained by numerical simulation. And, the above laws are verified by design experiments. It is found that the cutting speed, feed rate leaves a significant impact on the law of variations of oil film performance with time. According to the conclusions, it will be beneficial to improve the bearing capacity of the hydrostatic turntable and further improve the machining accuracy by using cutting parameters reasonably to control the speed within a certain range. [ABSTRACT FROM AUTHOR]

Abstract Background Chronic hepatitis B virus (HBV) infection-reduced liver functions are associated with intestinal microbial community dissimilarity. This study aimed to investigate the microbial community dissimilarity in patients with different grades of HBV-related liver cirrhosis. Results Serum endotoxin was increased with Child–Pugh (CP) class (A, B, and C). Veillonellaceae and Lachnospiraceae families were reduced in patients compared with controls. Megamonas and Veillonella genus was reduced and increased in patients compared with controls, respectively, especially in CPB and CPC groups. Correlation analysis showed that endotoxin content was significantly correlated with alcohol consumption (95% CI 0.100, 0.493), CP class (95% CI 0.289, 0.687) and Lachnospiraceae family level (95% CI − 0.539, − 0.122). Firmicutes/Bacteroidetes ratio was correlated with the level of Lachnospiraceae family (95% CI 0.013, 0.481), Veillonellaceae family (95% CI 0.284, 0.696), Megamonas genus (95% CI 0.101, 0.518) and Veillonella genus (95% CI 0.134, 0.545). All aforementioned bacteria were independent risk or protective factors for hepatitis. Alcohol consumption changed microbial community. Conclusions Our study demonstrated that elevated Firmicutes/Bacteroidetes ratio, reduced Megamonas genus level and increased Veillonella genus level were indicators for HBV-related liver cirrhosis. Alcohol-related pathogenesis was associated with the changed microbial community.

Abstract Background Icariside D2 is a plant-derived natural glycoside with pharmacological activities of inhibiting angiotensin-converting enzyme and killing leukemia cancer cells. Production of icariside D2 by plant extraction and chemical synthesis is inefficient and environmentally unfriendly. Microbial cell factory offers an attractive route for economical production of icariside D2 from renewable and sustainable bioresources. Results We metabolically constructed the biosynthetic pathway of icariside D2 in engineered Escherichia coli. We screened the uridine diphosphate glycosyltransferases (UGTs) and obtained an active RrUGT3 that regio-specifically glycosylated tyrosol at phenolic position to exclusively synthesize icariside D2. We put heterologous genes in E. coli cell for the de novo biosynthesis of icariside D2. By fine-tuning promoter and copy number as well as balancing gene expression pattern to decrease metabolic burden, the BMD10 monoculture was constructed. Parallelly, for balancing pathway strength, we established the BMT23–BMD12 coculture by distributing the icariside D2 biosynthetic genes to two E. coli strains BMT23 and BMD12, responsible for biosynthesis of tyrosol from preferential xylose and icariside D2 from glucose, respectively. Under the optimal conditions in fed-batch shake-flask fermentation, the BMD10 monoculture produced 3.80 g/L of icariside D2 using glucose as sole carbon source, and the BMT23–BMD12 coculture produced 2.92 g/L of icariside D2 using glucose–xylose mixture. Conclusions We for the first time reported the engineered E. coli for the de novo efficient production of icariside D2 with gram titer. It would be potent and sustainable approach for microbial production of icariside D2 from renewable carbon sources. E. coli–E. coli coculture approach is not limited to glycoside production, but could also be applied to other bioproducts.

Backgrounds and aims: Increased arterial stiffness may increase cardiovascular morbidity and mortality. Angiotensin II type 1 receptor blockers (ARBs) are potentially useful in controlling the central blood pressure and arterial stiffness in mild to moderate essential hypertension, while the effects of ARBs in aged patients with essential hypertension are not entirely investigated. Methods: The carotid-femoral arterial pulse wave velocity (PWV) was measured in aged patients with essential hypertension. Results: In a cross-sectional study, PWV value was significantly higher in these old patients with essential hypertension, compared to patients without essential hypertension. In correlation analysis, PWV was associated positively with age, hypertension duration, and carotid atherosclerosis. However, there was no relationship between PWV and gender in aged patients with essential hypertension. In a perspective study, 6–12 months administration of ARBs (losartan, 50 mg/day; telmisartan, 40 mg/day; valsartan 80 mg/day; irbesartan, 150 mg/day) remarkably reduced PWV in aged patients with essential hypertension. Regression analyses of multiple factors indicated that the effects of ARBs on arterial stiffness were not associated with the reduction of blood pressure. Conclusion: ARB treatment is a negative risk factor of arterial stiffness in aged patients with essential hypertension.

Abstract Background Increasing evidence has suggested that the cerebellum is associated with pain and migraine. In addition, the descending pain system of the brainstem is the major site of trigeminal pain processing and modulation and has been discussed as a main player in the pathophysiology of migraine. Cerebellar and brainstem structural changes associated with migraineurs remain to be further investigated. Methods Voxel-based morphometry (VBM) (50 controls, 50 migraineurs without aura (MWoAs)) and diffusion tensor imaging (DTI) (46 controls, 46 MWoAs) were used to assess cerebellum and brainstem anatomical alterations associated with MWoAs. We utilized a spatially unbiased infratentorial template toolbox (SUIT) to perform cerebellum and brainstem optimized VBM and DTI analysis. We extracted the average diffusion values from a probabilistic cerebellar white matter atlas to investigate whether MWoAs exhibited microstructure alterations in the cerebellar peduncle tracts. Results MWoAs showed decreased fractional anisotropy (FA) in the vermis VI extending to the bilateral lobules V and VI of the cerebellum. We also found higher axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD) in the right inferior cerebellum peduncle tract in MWoAs. MWoAs exhibited both reduced gray matter volume and increased AD, MD and RD in the spinal trigeminal nucleus (SpV). Conclusion MWoAs exhibited microstructural changes in the cerebellum and the local brainstem. These structural differences might contribute to dysfunction of the transmission and modulation of noxious information, trigeminal nociception, and conduction and integration of multimodal information in MWoAs. These findings further suggest involvement of the cerebellum and the brainstem in the pathology of migraine without aura.

Abstract Background Alpha-Terpineol (α-Terpineol), a C10 monoterpenoid alcohol, is widely used in the cosmetic and pharmaceutical industries. Construction Saccharomyces cerevisiae cell factories for producing monoterpenes offers a promising means to substitute chemical synthesis or phytoextraction. Results α-Terpineol was produced by expressing the truncated α-Terpineol synthase (tVvTS) from Vitis vinifera in S. cerevisiae. The α-Terpineol titer was increased to 0.83 mg/L with overexpression of the rate-limiting genes tHMG1, IDI1 and ERG20 F96W-N127W . A GSGSGSGSGS linker was applied to fuse ERG20F96W-N127W with tVvTS, and expressing the fusion protein increased the α-Terpineol production by 2.87-fold to 2.39 mg/L when compared with the parental strain. In addition, we found that farnesyl diphosphate (FPP) accumulation by down-regulation of ERG9 expression and deletion of LPP1 and DPP1 did not improve α-Terpineol production. Therefore, ERG9 was overexpressed and the α-Terpineol titer was further increased to 3.32 mg/L. The best α-Terpineol producing strain LCB08 was then used for batch and fed-batch fermentation in a 5 L bioreactor, and the production of α-Terpineol was ultimately improved to 21.88 mg/L. Conclusions An efficient α-Terpineol production cell factory was constructed by engineering the S. cerevisiae mevalonate pathway, and the metabolic engineering strategies could also be applied to produce other valuable monoterpene compounds in yeast.

Five crop straws (wheat, rice, maize, oil-rape, and cotton) were first steam-exploded for 2 min at 210°C, 2.5 MPa and then pyrolyzed at 500°C for 2 h. Steam explosion (SE) induced 47–95% and 5–16% reduction of hemicellulose and cellulose, respectively, in the crop straws. The biochars derived from SE-treated feedstocks had a lower specific surface area (SSA) and pore volume, compared to those from pristine feedstocks, with one exception that SE enhanced SSA of oil-rape straw biochar by approximately 16 times. After SE, biochars had significant higher anion exchange capacity (AEC) (6.88–11.44 cmol kg–1) and point of zero net charges (PZNC) (pH 3.61–5.32) values. It can thus be speculated that these biochars may have higher potential for anions adsorption. In addition, oil-rape straw might be suitable to SE pretreatment for preparing biochar as a soil amendment and sorbent as well. Further work is required for testing its application in soil.

Designing large-scale crossbar arrays for energy efficient neuromorphic computing systems remains a challenge. Here, the authors propose Van der Waals (h-BN/graphene/h-BN) self-selective memory design able to combine, in the same cell, non-volatile and volatile behaviors with negligible sneak current.

Disruption of the blood–brain barrier (BBB) has been considered as a major pathological change in stroke. eNOS/NO play a key role in maintain BBB function. Myricetin is one of the common flavones widely exists in food and fruit, show certain protective effect on the brain function. This experiment establishes oxygeneglucose deprivation and reoxygenation (OGD/R) brain cell model. The regulated effects of Myricetin on BBB function, eNOS/NO and eNOS uncoupling were evaluated. To investigate the molecular mechanism, Akt and Nrf2 inhibitor were also used. The result showed that Myricetin could significantly decreased the enhancement of endothelial permeability and inflammation in OGD/R model, in addition regulated eNOS/NO pathway. The regulate effect in endothelial permeability and eNOS activity by Myricetin were both decreased when combined with Akt inhibitor or Nrf2 inhibitor, and was abrogated when combined with Akt and Nrf2 inhibitor simultaneously. The regulated effect on eNOS uncoupling by Myricetin were abrogated when combined with Nrf2 inhibitor, but not with Akt inhibitor. In conclusion, Myricetin showed significant protect effect on ischemia/reperfusion-induced brain endothelial permeability, and related to simultaneously regulated Akt pathway and improvement of eNOS uncoupling through Nrf2 pathway. Keywords: Ischemia/reperfusion injury, eNOS/NO, eNOS uncoupling, Myricetin

Multiple studies on regional glacier mass balance in the Pamir Mountains have been conducted using the geodetic method, but they were rarely extended to the period before 2000. In this study, we used KH-9 imagery acquired in 1975 to generate the historical DEM for the central Pamir, and then obtained the glacier elevation change by comparing this with the SRTM C-band DEM. The penetration depth of the C-band radar was corrected for different glacier surfaces, i.e. 2.96, 1.68 and 0 m for firn/snow cover, bare ice and debris-covered areas, respectively. The final results suggest that the central Pamir glaciers, overall, experienced a near-zero mass balance of −0.03 ± 0.24 m w.e. a−1 for 1975–99. Due to glacier surge activity, the elevation change patterns of individual glaciers were highly variable, and their mass balances varied from −0.12 ± 0.26 to 0.63 ± 0.20 m w.e. a−1. The mean mass budgets of the surge-type glaciers and non-surge-type glaciers were 0.03 ± 0.14 and −0.05 ± 0.28 m w.e. a−1, respectively. Concurring with previous studies, we conclude that the central Pamir glaciers may have been in a state of approximately balanced mass budget or slight mass deficit from the mid-1970s to the mid-2010s.

Abstract Background Diterpenoids are a large class of natural products with complex structures and broad commercial applications as food additives, important medicines, and fragrances. However, their low abundance in plants and high structural complexity limit their applications. Therefore, it is important to create an efficient diterpenoid-producing yeast cell factory of the production of various high-value diterpenoid compounds in a cost-effective manner Results In this study, 13R-manoyl oxide (13R-MO; 2.31 mg/L) was produced by expressing CfTPS2 and CfTPS3 from Coleus forskohlii in Saccharomyces cerevisiae. The 13R-MO titer was increased by 142-fold to 328.15 mg/L via the stepwise metabolic engineering of the original strain, including the overexpression of the rate-limiting genes (tHMG1 and ERG20) of the mevalonate pathway, transcription and protein level regulation of ERG9, Bts1p and Erg20F96Cp fusion, and the overexpression of tCfTPS2 and tCfTPS3 (excision of the N-terminal plastid transit peptide sequences of CfTPS2 and CfTPS3). The final titer of 13R-MO reached up to 3 g/L by fed-batch fermentation in a 5 L bioreactor. Conclusions In this study, an efficient 13R-MO yeast cell factory was constructed, which achieved the de novo production of 3 g/L of 13R-MO from glucose. To the best of our knowledge, this is the highest 13R-MO titer reported to date. Furthermore, the metabolic engineering strategies presented here could be used to produce other valuable diterpenoid compounds in yeast.

Background: Zuotai (mainly β-HgS)-containing 70 Wei-Zhen-Zhu-Wan (70W, Rannasangpei) is a famous Tibetan medicine for treating cardiovascular and gastrointestinal diseases. We have shown that 70W protected against CCl 4 hepatotoxicity. CCl 4 is metabolized via cytochrome P450 (CYP) to produce reactive metabolites. Whether 70W has any effect on CYPs is unknown and such effects should be compared with mercury compounds for safety evaluation. Methods: Mice were given clinical doses of 70W (0.15-1.5 g/kg, po), Zuotai (30 mg/kg, po), and compared to HgCl 2 (33.6 mg/kg, po) and MeHg (3.1 mg/kg, po) for seven days. Liver RNA and protein were isolated for qPCR and Western-blot analysis. Results: 70W and Zuotai had no effects on hepatic mRNA expression of Cyp1a2, Cyp2b10, Cyp3a11, Cyp4a10 and Cyp7a1, and corresponding nuclear receptors [aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), pregnane X receptor (PXR), peroxisome proliferator-activated receptor-α (PPARα); farnesoid X receptor (FXR)]. In comparison, HgCl 2 and MeHg increased mRNA expression of Cyp1a2, Cyp2b10, Cyp4a10 and Cyp7a1 except for Cyp3a11, and corresponding nuclear receptors except for PXR. Western-blot confirmed mRNA results, showing increases in CYP1A2, CYP2B1, CYP2E1, CYP4A and CYP7A1 by HgCl 2 and MeHg only, and all treatments had no effects on CYP3A. Conclusions: Zuotai and Zuotai-containing 70W at clinical doses had minimal influence on hepatic CYPs and corresponding nuclear receptors, while HgCl 2 and MeHg produced significant effects. Thus, the use of total Hg content to evaluate the safety of HgS-containing 70W is inappropriate.

Eliminating poverty is the primary goal of sustainable development. China has eliminated absolute poverty in 2020, yet there is a chance that it could happen again. The poor population is mostly concentrated in ecologically fragile areas. We need to take more inclusive and effective initiatives to prevent the population in ecologically fragile areas from returning to poverty. In this study, a decision tree and logistic regression model were used to assess the risk of returning to poverty in Karst ecologically fragile areas. The data comes from 303 households in four counties in Guizhou and Guangxi. There are 12 main influencing factors identified, with the percentage of workforce numbers and loans having interactive effects. The results show that: (1) Poor resilience of livelihood assets, external shocks, and the effects of some support measures will be visible after a long period, leading to "transient" poverty and return to poverty. (2) Ecological environment management in ecologically fragile areas is very important to solve the problem of returning to poverty. (3) Appropriate loans can reduce poverty, especially when loans are used to cultivate a new excellent labor force. At the same time, it is necessary to evaluate farmers’ repayment ability reasonably and scientifically to reduce the risk of returning to poverty. The combination of ecological restoration and agricultural development is the key to solving ecological and social problems in Karst areas. Efforts should be made to improve the risk-resilience of farmers’ livelihood assets and the efficiency of livelihood assets utilization by implementing targeted support measures. This research provides a new approach to studying the mechanism of poverty recurrence, which is of great practical significance for consolidating the results of poverty eradication and realizing rural vitalization.

This paper describes an extensive experimental study of the compressive failure of different types of aggregates and the influence of aggregate type on the interfacial properties of mortars. Interfacial debonding was the main failure mode of mortar rubbles. The interlocking strength of aggregate and mortar strongly affected the compressive strength of materials. When basalt was used as the aggregate, I-II composite failure of the deflection crack occurred as well as interfacial debonding. The highest instantaneous AE energy of the granite mortar rubble was 1349 mV·ms, which was 4.1 times greater than that of the basalt mortar rubble (326 mV·ms). Acoustic emissions of mortar rubble were strongest in the 150–220 kHz range and gave an early warning of the damage load at high frequencies (160–320 kHz). The C-S-H gel formed by the hydration reaction adhered to the aggregate pores and exhibited a “root pile” effect that improved the bonding performance of the interfacial zone. The interfacial porosity of the basalt, granite and limestone mortar rubble was 21.29%, 18.70% and 30.0%, respectively. The limestone interface has a large porosity, the fractal cones was small (1.19), and there was an obvious sidewall effect, but the interfacial strength was weak. The pore structure had a significant effect on the interfacial bond strength. This multi-faceted analysis truly reflected the state and evolution of the damage of mortar rubbles, and the results were very effective for determining the mechanical mode of damage of mortar rubbles.

Current aerodynamic parameter identification methods take the consistency between the response of the motion model reconstructed with the identified aerodynamic parameters and flight data as an optimization index. Since there is only one index constraint in aerodynamic parameter optimization, and more than ten aerodynamic parameters to be identified simultaneously have different sensitivity to the optimization index, the accuracy of identification results of parameters with low sensitivity is poor, especially for those with small absolute value. To solve these problems, a new idea, having aerodynamic parameters solved by balance equations and identified in stages, is proposed. Based on the motion characteristics of different lateral-directional maneuvers, the scheme of combined maneuvers is designed, and the step-by-step identification procedure is established. An estimation method of angular acceleration with angular velocity equivalent model is proposed to solve the problem that angular acceleration cannot be measured directly. A lateral-directional aerodynamic parameter identification method using segmented adaptation of flight data and identification models is established based on the identifiability of flight data. The lateral-directional aerodynamic parameter identification results of a large civil aircraft show the identification results can be obtained with higher accuracy by adopting the proposed identification method and the flight test scheme.

Genistein, a nutraceutical isoflavone, has various pharmaceutical and biological activities which benefit human health via soy-containing food intake. This study aimed to construct Saccharomyces cerevisiae to produce genistein from sugar via a modular engineering strategy. In the midstream module, various sources of chalcone synthases and chalcone isomerase-like proteins were tested which enhanced the naringenin production from p-coumaric acid by decreasing the formation of the byproduct. The upstream module was reshaped to enhance the metabolic flux to p-coumaric acid from glucose by overexpressing the genes in the tyrosine biosynthetic pathway and deleting the competing genes. The downstream module was rebuilt to produce genistein from naringenin by pairing various isoflavone synthases and cytochrome P450 reductases. The optimal pair was used for the de novo biosynthesis of genistein with a titer of 31.02 mg/L from sucrose at 25 °C. This is the first report on the de novo biosynthesis of genistein in engineered S. cerevisiae to date. This work shows promising potential for producing flavonoids and isoflavonoids by modular metabolic engineering.

Accurate ranging and real-time temperature monitoring are essential for metrology and safety in electrical conduit applications. This paper proposes an acoustic time-of-flight (TOF) estimation method based on the digital lock-in filtering (DLF) technique for conduit ranging and thermometry. The method establishes the relationship between the frequency and the time domain by applying a linear frequency modulated Chirp signal as the sound source and using the DLF technique to extract the first harmonic of the characteristic frequencies of the transmitted and received signals. Acoustic TOF estimation in the conduit is then achieved by calculating the mathematical expectation of the time difference between each characteristic frequency in the time-frequency relationship of the two signals. The experimental results with enhanced noise interference on different conduit lengths and various temperature conditions, proved that the proposed DLF method can establish a robust linear time-frequency relationship according to the characteristics of the Chirp signal, and the measurement accuracy of TOF has also been confirmed. Compared to the conventional method, the DLF method provides the lowest absolute error and standard deviation for both distance and temperature measurements with an enhanced robustness.

7-Dehydrocholesterol (7-DHC) is the direct precursor to manufacture vitamin D3. Our previous study has achieved 7-DHC synthesis in Saccharomyces cerevisiae based on the endogenous post-squalene pathway. However, the distribution of post-squalene enzymes between the endoplasmic reticulum (ER) and lipid bodies (LD) might raise difficulties for ERG proteins to catalyze and deliver sterol intermediates, resulting in unbalanced metabolic flow and low product yield. Herein, we intended to rearrange the subcellular location of post-squalene enzymes to alleviate metabolic bottleneck and boost 7-DHC production. After identifying the location of DHCR24 (C-24 reductase, the only heterologous protein for 7-DHC biosynthesis) on ER, all the ER-located enzymes were grouped into four modules: ERG1/11/24, ERG25/26/27, ERG2/3, and DHCR24. These modules attempted to be overexpressed either on ER or on LDs. As a result, expression of LD-targeted DHCR24 and ER-located ERG1/11/24 could promote the conversion efficiency among the sterol intermediates to 7-DHC, while locating module ERG2/3 into LDs improved the whole metabolic flux of the post-squalene pathway. Coexpressing LD-targeted ERG2/3 and DHCR24 (generating strain SyBE_Sc01250035) improved 7-DHC production from 187.7 to 308.2 mg/L at shake-flask level. Further expressing ER-targeted module ERG1/11/24 in strain SyBE_Sc01250035 dramatically reduced squalene accumulation from 620.2 mg/L to the lowest level (by 93.8%) as well as improved 7-DHC production to the highest level (to 342.2 mg/L). Then targeting module ERG25/26/27 to LDs further increased 7-DHC titer to 360.6 mg/L, which is the highest shake-flask level production for 7-DHC ever reported. Our study not only proposes and further proves the concept of pathway compartmentalized reconstitution to regulate metabolic flux but also provides a promising chassis to produce other steroidal compounds through the post-squalene pathway.

Background: As one of the main participants in health care, nurses are esteemed an important driving force for the vigorous health care development. Studies report that nurses’ proactive personality has positive effects on their job performance; however, this relationship acquires further understanding.Objective: A cross-sectional study was performed to explore the relationship between nurses’ proactive personality and job performance; the mediating role of nurses’ competency and work engagement in this relationship was also evaluated.Methods: The study was performed in a large third-degree general hospital in October 2019, Xi’an, PR, China. A sample of 246 nurses participated in this cross-sectional study. Proactive personality was assessed with the Proactive Personality Questionnaire (PPS), job performance was assessed by Heilman three-item measurements, nurse competence was estimated with Nurse Competency Scale (NCS), and work engagement was assessed with the Utrecht Work Engagement Scale (UWES). The structural equation model was used to test the main hypotheses.Results: Structural equation model analysis revealed that work engagement partially mediated the association between proactive personality and job performance. The serial two-mediator model which was used to explore the association between proactive personality and job performance through competency and work engagement, in sequence, was demonstrated.Conclusion: This study demonstrates that work engagement partially mediated the association between nurses’ proactive personality and their job performance. The serial two-mediator model demonstrated that proactive personality was associated with job performance via competency and work engagement. This study also revealed the critical role of nursing managers in understanding the nurses’ proactive personality, which would facilitate them to enhance the latter’s competency and promote their work engagement. All these will in turn constantly improve the overall quality of nursing and advance professional development of nursing and benefits for patients.

Epilepsy is a chronic disease that can cause temporary brain dysfunction as a result of sudden abnormal discharge of the brain neurons. The seizure mechanism of epilepsy is closely related to the neurotransmitter imbalance, synaptic recombination, and glial cell proliferation. In addition, epileptic seizures can lead to mitochondrial damage, oxidative stress, and the disorder of sugar degradation. Although the mechanism of epilepsy research has reached up to the genetic level, the presently available treatment and recovery records of epilepsy does not seem promising. Recently, natural medicines have attracted more researches owing to their low toxicity and side-effects as well as the excellent efficacy, especially in chronic diseases. In this study, the antiepileptic mechanism of the bioactive components of natural drugs was reviewed so as to provide a reference for the development of potential antiepileptic drugs. Based on the different treatment mechanisms of natural drugs considered in this review, it is possible to select drugs clinically. Improving the accuracy of medication and the cure rate is expected to compensate for the shortage of the conventional epilepsy treatment drugs.

Integration of computer-science oriented artificial neural networks (ANNs) and neuroscience oriented spiking neural networks (SNNs) has emerged as a highly promising direction to achieve further breakthroughs in artificial intelligence through complementary advantages. This integration needs to support individual modeling of ANNs and SNNs as well as their hybrid modeling, which not only simultaneously calculates single-paradigm networks but also converts their different information representations. It remains challenging to realize effective calculation and signal conversion on the existing dedicated hardware platforms. To solve this problem, we propose an end-to-end mapping framework for implementing various hybrid neural networks on many-core neuromorphic architectures based on the cross-paradigm Tianjic chip. We construct hardware configuration schemes for four typical signal conversions and establish a global timing adjustment mechanism among different heterogeneous modules. Experimental results show that our framework can implement these hybrid models with low execution latency and low power consumption with nearly no accuracy degradation. This work provides a new approach of developing hybrid neural network models for brain-inspired computing chips and further tapping the potential of these models.

In the case of earthquake and rockfall disasters, it is proposed to replace part of sand with geofoam material to form sand–EPS and sand–EPE composite cushions to improve the ability of structures to resist disasters. The shear performance of the sand–EPS beads mixture material with different moisture contents, the impact resistance of sand–EPS beads and sand–flocculent-EPE layered composite materials with different cushion thicknesses and different mass ratios were studied by direct shear tests and multi-impact tests. The results showed that with the increase in the moisture content, the shear strength of the sand–EPS beads decreased, the internal friction angle of sand–EPS decreased first and then increased, and the cohesion of sand–EPS increased first and then decreased. The sand–geofoam layered cushion had better buffering performance. Sand–EPE has better durability than Sand–EPS.