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The inducible CRISPR activation (CRISPR-a) system offers unparalleled precision and versatility for regulating endogenous genes, making it highly sought after in plant research. In this study, we developed a chemically inducible CRISPR-a tool for plants called ER-Tag by combining the LexA-VP16-ER inducible system with the SunTag CRISPR-a system. We systematically compared different induction strategies and achieved high efficiency in target gene activation. We demonstrated that guide RNAs can be multiplexed and pooled for large-scale screening of effective morphogenic genes and gene pairs involved in plant regeneration. Further experiments showed that induced activation of these morphogenic genes can accelerate regeneration and improve regeneration efficiency in both eudicot and monocot plants, including alfalfa, woodland strawberry, and sheepgrass. Our study expands the CRISPR toolset in plants and provides a powerful new strategy for studying gene function when constitutive expression is not feasible or ideal.

Abstract Neurotrophic tyrosine kinase (NTRK) fusions involving NTRK1, NTRK2, and NTRK3 were found in a broad range of solid tumors as driver gene variants. However, the prevalence of NTRK fusions in Chinese solid tumor patients is rarely reported. Based on the next-generation sequencing data from 10,194 Chinese solid tumor patients, we identified approximately 0.4% (40/10,194) of Chinese solid tumor patients with NTRK fusion. NTRK fusions were most frequently detected in soft tissue sarcoma (3.0%), especially in the fibrosarcoma subtype (12.7%). A total of 29 NTRK fusion patterns were identified, of which 11 were rarely reported. NTRK fusion mostly co-occurred with TP53 (38%), CDKN2A (23%), and ACVR2A (18%) and rarely with NTRK amplification (5.0%) and single nucleotide variants (2.5%). DNA-based NTRK fusion sequencing exhibited a higher detection rate than pan-TRK immunohistochemistry (100% vs. 87.5%). Two patients with NTRK fusions showed clinical responses to larotrectinib, supporting the effective response of NTRK fusion patients to TRK inhibitors.

To address the issues of corrosion weakening of solid-waste-based backfill material caused by mine water, a novel hydrophobic solid waste backfill (HSBF) material was developed using polydimethylsiloxane (PDMS) and a silane coupling agent (SCA) as hydrophobic modification additives, and NaOH (SH) and sodium silicate (SS) as alkali activators. Fly ash and slag were chosen as the primary raw solid waste materials. The rheological properties of the hydrophobic-treated backfill slurries were measured, and the resulting physicochemical properties were compared with the unmodified reference group. This study reveals that the fresh HSBF slurry follows a Modified Bingham (M-B) model with shear-thinning characteristics. The addition of PDMS causes an increase in the water contact angle of the hardened HSBF material with F8S2 to up to 134.9°, indicating high hydrophobicity. Morphological observations indicated that PDMS mainly attaches to the inorganic particles’ surface through the bridging action of SCA for the hydrophobic modification of the backfill material. The overall strength of the HSBF materials was further ensured via fly ash–slag ratio optimization, and was found to be enhanced up to 98% by increasing slag content from 20% to 50%. This is mainly attributed to the hydration of slag, forming C-S(A)-H gel, which contributes to the increased strength. The novel HSBF material enables the elimination of cement in mine backfilling applications, demonstrating good economic benefits. Its excellent mechanical and hydrophobic properties can not only prevent overburden displacement in goaf areas, but can also mitigate water resource loss from overlying strata and simultaneously reduce the safety risks associated with long-term mine water deterioration.

The orientated Mg-4.70Zn-0.38Y-0.14Zr alloy with high product of strength and elongation (PSE = 5346 MPa•%) was prepared using directional solidification technology. Electron Back Scatter Diffraction (EBSD) and High Resolution Transmission Electron Microscopy (HRTEM) were applied to explore the deformation mechanism and plasticity improvement of experimental alloys. Experiment results showed that the dominant deformation systems were non-basal slipping systems and compression twin pairs (CTPs). High critical resolved shear stress (CRSS) of non-basal slipping system increased the yield strength (180 MPa) and tensile strength (198 MPa). The CTP followed the geometrical relationship of TP1 (twinning plane of variant1)∥TP2 (twinning plane of variant2) and appeared in a wider misorientation range than tensile twin pair which was classified as twinning shear transmission and had high geometric coordination factor (m’). Calculation results showed that the stress concentration at the junction of CTP and grain boundaries was the same as inside the compression twin. 60% of x/ (0°≤x

Abstract Background The prediction accuracy of pulse pressure variation (PPV) for fluid responsiveness was proposed to be unreliable in low tidal volume (Vt) ventilation. It was suggested that changes in PPV obtained by transiently increasing Vt to 8 ml/kg accurately predicted fluid responsiveness even in subjects receiving low Vt. We assessed whether the changes in PPV induced by a Vt challenge predicted fluid responsiveness in our critically ill subjects ventilated with low Vt 6 ml/kg. Methods This study is a prospective single-center study. PPV and other parameters were measured at a Vt of 6 mL/kg, 8 mL/kg, and after volume expansion. The prediction accuracy of PPV and other parameters for fluid responsiveness before and after tidal volume challenge was also analyzed using receiver operating characteristic (ROC) curves. Results Thirty-one of the 76 subjects enrolled in the study were responders (41%). Respiratory system compliance of all subjects decreased significantly (26 ± 4.3). The PPV values were significantly higher in the responder group than the non-responder group before (8.8 ± 2.7 vs 6.8 ± 3.1) or after (13.0 ± 1.7 vs 8.5 ± 3.0) Vt challenge. In the receiver operating characteristic curve (ROC) analysis, PPV6 showed unsatisfactory predictive capability with an area under the curve (AUC) of 0.69 (95%CI, 0.57–0.79, p = 0.002) at a Vt of 6 mL/kg. PPV8 andΔPPV6–8 showed good predictive capability with an AUC of 0.90 (95% CI, 0.81–0.96, p

FLNC, encoding filamin C, is one of the most mutated genes in dilated and hypertrophic cardiomyopathy. However, the precise role of filamin C in mammalian heart remains unclear. In this study, we demonstrated Flnc global (FlncgKO) and cardiomyocyte-specific knockout (FlnccKO) mice died in utero from severely ruptured ventricular myocardium, indicating filamin C is required to maintain the structural integrity of myocardium in the mammalian heart. Contrary to the common belief that filamin C acts as an integrin inactivator, we observed attenuated activation of β1 integrin specifically in the myocardium of FlncgKO mice. Although deleting β1 integrin from cardiomyocytes did not recapitulate the heart rupture phenotype in Flnc knockout mice, deleting both β1 integrin and filamin C from cardiomyocytes resulted in much more severe heart ruptures than deleting filamin C alone. Our results demonstrated that filamin C works in concert with β1 integrin to maintain the structural integrity of myocardium during mammalian heart development.

Abstract Background Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. The liver has a crucial role in sepsis and is also a target for sepsis-related injury. Macrophage polarization between the M1 and M2 types is involved in the progression and resolution of both inflammation and liver injury. Iron oxide-based synthetic nanoparticles (SPIONs) can be used as antibacterial agents to regulate the inflammatory response. Mesenchymal stromal/stem cells (MSCs) have been widely used in the treatment of autoimmune diseases, sepsis, and other diseases. However, to date, both the effects of SPIONs on MSCs and the fate of SPION-labelled MSCs in sepsis and other diseases are still unclear. Methods Mice were subjected to caecal ligation and puncture (CLP) or lipopolysaccharide (LPS) induction to develop sepsis models. The CLP or LPS models were treated with MSCs or SPION-labelled/pretreated MSCs (SPION-MSCs). Bone marrow (BM)-derived macrophages and RAW 264.7 cells were cocultured with MSCs or SPION-MSCs under different conditions. Flow cytometry, transmission electron microscopy, western blotting, quantitative real-time PCR, and immunohistochemical analysis were performed. Results We found that SPIONs did not affect the basic characteristics of MSCs. SPIONs promoted the survival of MSCs by upregulating HO-1 expression under inflammatory conditions. SPION-MSCs enhanced the therapeutic efficacy of liver injury in both the CLP- and LPS-induced mouse models of sepsis. Moreover, the protective effect of SPION-MSCs against sepsis-induced liver injury was related to macrophages. Systemic depletion of macrophages reduced the efficacy of SPION-MSC therapy. Furthermore, SPION-MSCs promoted macrophages to polarize towards the M2 phenotype under sepsis-induced liver injury in mice. The enhanced polarization towards M2 macrophages was attributed to their phagocytosis of SPION-MSCs. SPION-MSC-expressed TRAF1 was critical for promotion of macrophage polarization and alleviation of sepsis in mice. Conclusion MSCs labelled/pretreated with SPIONs may be a novel therapeutic strategy to prevent or treat sepsis and sepsis-induced liver injury. Highlights 1. SPIONs enhance the viability of MSCs by promoting HO-1 expression. 2. SPION-labelled/pretreated MSCs effectively improve sepsis by regulating macrophage polarization to M2 macrophages. 3. SPION-labelled/pretreated MSCs regulate macrophage polarization in a manner dependent on MSC-expressed TRAF1 protein.

Abstract Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease. Myeloid-derived suppressor cells (MDSCs) have been found to be involved in the regulation of SLE development. However, little is known about the association between MDSC subsets and the factors that draw MDSCs into abnormal expansion. This study found that the percentage of M-MDSCs increased in mice with pristane-induced lupus. Toll-like receptor (TLR)7 signal activation and high interferon-α (IFN-α) level promoted M-MDSC differentiation in vitro. Moreover, both AMP-activated protein kinase (AMPK) agonist metformin and two mammalian targets of rapamycin (mTOR) inhibitors (INK128 and rapamycin) inhibited the percentage of M-MDSCs in lupus mice as well as in the TLR7- and IFN-α-induced bone marrow (BM) differentiation into MDSCs in vitro. In terms of mechanism, whole-genome transcriptome profiling was performed by RNA sequencing, revealing that the expression of the transcription factor IRF-8 was higher in M-MDSCs isolated from pristane-induced lupus mice, compared with control mice. IRF-8 was identified to be crucial for TLR7- and IFN-α-induced BM differentiation into MDSCs in vitro. Furthermore, interferon (IFN) regulatory factor8 (IRF-8) was targeted by miR-451a in M-MDSC differentiation. Of note, metformin-modified M-MDSCs could relieve lupus symptoms in pristane-induced lupus mice. The findings revealed a novel mechanism linking IRF-8/miR-451a to M-MDSC differentiation via the AMPK/mTOR signal pathway during lupus development. This study might provide an important reference for SLE therapy by targeting M-MDSCs.

Abstract Background Skin wounds in diabetic patients hardly recover. Accumulating evidence has shown that mammalian target of rapamycin (mTOR) pathway and myeloid-derived suppressor cells (MDSCs) are involved in inflammatory-related response. INK128 is a novel mTOR kinase inhibitor in clinical development. However, the exact roles of MDSCs and INK128 in healing wound of diabetic patients are unclear. Methods Mice models of normal, diabetic, and diabetic+INK128 were constructed. Bone marrow (BM)-derived macrophages and RAW264.7 cell line co-cultured with MDSCs, which were induced at different conditions. Flow cytometry, western blot, quantitative real-time PCR, and immunohistochemical analysis were performed. Results Diabetic mice (DM) had a slower recovery rate, thinner epidermis and dermis, and less blood vessels than those of normal mice. MDSCs were abnormally accumulated in DM, mTOR was activated in MDSCs of DM, and the cells were treated with high glucose. Moreover, mTOR signaling inhibitor INK128 could promote wound healing through reducing the MDSCs. MDSC function was disordered in DM and high-glucose environments, while INK128 could help retrieve their function. Furthermore, high glucose and other factors in DM could promote M-MDSC differentiation to M1 pro-inflammatory macrophage cells, thus inhibiting wound healing. The differentiation, which was dependent on mTOR signaling, could be reversed by INK128. Conclusion INK128 is potential to be developed as a clinical strategy to promote wound healing of diabetic patients.

Abstract Background At present, the treatment of recurrent glioblastoma is extremely challenging. In this study, we used a novel three-dimensional non-coplanar template (3DNPT) combined with open MR to guide 125I seed implantation for recurrent glioblastoma. The aim of this study was to evaluate the feasibility, accuracy, and effectiveness of this technique. Methods Twenty-four patients of recurrent glioblastoma underwent 3DNPT with open MR-guided 125I brachytherapy from August 2017 to January 2019. Preoperative treatment plan and 3DNPT were made according to enhanced isovoxel T1-weighted MR images. 125I seeds were implanted using 3DNPT and 1.0-T open MR imaging guidance. Dosimetry verification was performed after brachytherapy based on postoperative CT/MR fusion images. Preoperative and postoperative dosimetry parameters of D90, V100, V200, conformity index (CI), external index (EI) were compared. The objective response rate (ORR) at 6 months and 1-year survival rate were calculated. Median overall survival (OS) measured from the date of brachytherapy was estimated by Kaplan-Meier method. Results There were no significant differences between preoperative and postoperative dosimetry parameters of D90, V100, V200, CI, EI (P > 0.05). The ORR at 6 months was 75.0%. The 1-year survival rate was 58.3%. Median OS was 12.9 months. One case of small amount of epidural hemorrhage occurred during the procedure. There were 3 cases of symptomatic brain edema after brachytherapy treatment, including grade three toxicity in 1 case and grade two toxicity in 2 cases. The three patients were treated with corticosteroid for 2 to 4 weeks. The clinical symptoms related to brain edema were significantly alleviated thereafter. Conclusions 3DNPT combined with open MR-guided 125I brachytherapy for circumscribed recurrent glioblastoma is feasible, effective, and with low risk of complications. Postoperative dosimetry matched the preoperative treatment plan. The described method can be used as a novel implantation technique for 125I brachytherapy in the treatment of recurrent gliomas. Trial registration The study was approved by the Institutional Review Board of Shandong Provincial Hospital Affiliated to Shandong University (NSFC:NO.2017–058), registered 1st July 2017.

Abstract Sepsis-induced immunosuppression is recognized as one of the main features responsible for therapeutic failures. Myeloid-derived suppressor cells (MDSCs), which are mainly characterized by their suppressive properties, have been reported to be expanded in sepsis. Ferumoxytol (FMT), an FDA-approved iron supplement, has been shown to possess immune-modulatory properties in tumors. However, it is unclear whether FMT alters the functions of MDSCs to reduce late-sepsis immunosuppression. Here, we showed an immunomodulatory effect of FMT on MDSCs to ameliorate lipopolysaccharide (LPS)–induced immunosuppression in the late stage of sepsis. Separation of cells with internalized FMT and detection of the intracellular iron content showed that MDSCs could uptake FMT. Low doses of FMT had no effects on the cell viability of MDSCs, but FMT inhibited the expansion of MDSCs in vitro. Moreover, FMT significantly downregulated the expression levels of Arg-1, S100A8, S100A9, and p47phox as well as ROS production in MDSCs. FMT decreased the percentage of granulocytic MDSCs (G-MDSCs) and promoted the differentiation of MDSCs into macrophages. Furthermore, FMT reduced white blood cell recruitment and alveolar wall thickening in the lungs and areas of necrosis in the liver as well as some biochemical markers of liver dysfunction. FMT decreased the percentage of G-MDSCs and monocytic MDSCs (M-MDSCs) in the spleens of LPS-induced septic mice. Of note, FMT reduced the T cell immunosuppressive functions of both G-MDSCs and M-MDSCs. Expectedly, FMT also significantly reduced Arg-1 and p47phox gene expression in splenic CD11b+Gr-1+ cells isolated from LPS-challenged mice. These data indicate that FMT decreased the immunosuppressive functions of MDSCs by decreasing Arg-1 and ROS production, suggesting that FMT may reduce long-term immunosuppression in the late stage of sepsis.

Coal mining under the aquifer in Northwest China has brought a series of ecological problems, such as the decline of groundwater levels and the death of surface vegetation. The study of the impermeability of rock strata between coal seams and the overlying aquifers is of great significance to solve these problems and realize water-preserving coal mining (WPCM). Based on mining-induced overburden damage and permeability deterioration, the concept of the “three seepage zones” of overburden is proposed, namely the pipe flow zone, water seepage zone and nominal water-seepage-resistance zone (NWSRZ). Meanwhile, the concept of water-seepage-resistance strata (WSRS) is put forward from the aspects of initial permeability, structural strength, swelling and the stratigraphic structure of the overlying strata. AHP-fuzzy comprehensive evaluation (AHPF) is employed to construct a model to evaluate the water-blocking capacity (WBC) of the WSRS. The model includes three secondary factors and nine tertiary indicators, and the weights and membership functions of the indicators are determined. Subsequently, the model is generalized and applied to the Yu-Shen mining area. The membership degrees are spatially visualized by means of thematic maps. The comprehensive evaluation values Φ of the WBCWSRS of 400 boreholes in the mining area under backfill mining, narrow strip mining, slice mining and longwall cave mining are calculated. Then, the Kriging method is employed to plot the zoning maps of Φ under four different mining methods. In view of different grades of WBCWSRS, three corresponding countermeasures, i.e., mining methods optimization, curtain grouting and underground reservoir construction, are put forward. The fluid–solid coupling embedded in FALC3D software is employed to establish a numerical calculation model to simulate the water table fluctuation of the underground aquifer under the four mining methods, and the reliability of the model is verified indirectly. In this paper, mathematical theory is combined with WPCM to develop an evaluation model of WBCWSRS, which provides a reference for the coordinated development of coal extraction and water resource preservation in arid and semi-arid mining areas.

The consumption of coal resources has caused an increase in CO2 emissions. A scientific concept that can realize CO2 sequestration, the harmless treatment of solid wastes, and coal extraction under buildings, railways, and water bodies (BRW) is proposed. First, a novel CO2 mineralized filling body (CMFB) is developed by employing CO2 gas, fly ash, silicate additives, and cement. It is then injected into the mined-out mining roadways (MRs) of the continuous extracting and continuous backfill (CECB) mining method to ameliorate the overburden migration and thus extract the coal body under the BRW. The AHP-fuzzy comprehensive evaluation method was employed to construct a prediction model for the suitability of this concept. Subsequently, the evaluation model is generalized and applied to the Yu-Shen mining area. Each indicator affecting adaptability is plotted on a thematic map, and the corresponding membership degree is determined. The aptness for 400 boreholes distributed in the entire area was determined and a zoning map which divides the whole area into good, moderate, slightly poor, and extremely poor suitability was drawn. This paper puts forward a mathematical model for predicting the suitability of using CECB and CMFB to sequestrate CO2. Research results can provide references for determining the site of CO2 sequestration under the premise of maximizing the economic and ecological benefits, which is conducive to constructing ecological, green, and sustainable coal mines.

Abstract In farmlands, most electronic devices have no connection to a power source and have to work on batteries. To explore paddy soil as an in situ power source, herein, we in the present study constructed sediment microbial fuel cells (SMFCs) in paddy soil. An open circuit voltage of 1.596 V and a maximum power density of 29.42 mWm−2 were obtained by serially connecting three SMFCs. Electrochemical impedance spectroscopy showed that the internal resistance which comprised ohmic resistance and anodic and cathodic charge transfer resistance was approximately 400 Ω for each of the three individual SMFCs. We used the serially connected SMFCs to power an electronic timer through a 1 F capacitor. The SMFCs had powered the timer for 80 h until the potential of the SMFCs dropped below 0.936 V. Then, RNA was extracted from anode samples and 16S rRNA was sequenced following reverse transcription. The results showed that the relative abundance of active exoelectrogenic bacteria-associated genera on the anode was 13.03%, 27.78%, and 16.17% for the three SMFCs with Geobacter and Anaeromyxobacter being the dominant genera. Our findings provide the possibility of powering electronic devices in the field by using soil as a power source.

Abstract Water-conserving mining is an effective way to alleviate the contradiction between fragile ecological environment and high-intensity coal mining in the arid and semi-arid region of northwest China. It needs to consider the engineering and geological conditions, hydrogeological conditions and mining methods of coal seams. From the three aspects, this paper systematically analyzes the influencing factors and establishes an identification model with multi-level structures. The model includes three primary factors (including the engineering and geological conditions, hydrogeological conditions and mining methods), nine secondary factors (including overlying strata thickness, aquiclude, mining parameters and etc.), sixteen third-tier factors (including the faults, aquiclude thickness and effective mining height and etc.) and twelve fourth-tier factors (including the fault throw exponent, aquiclude permeability and coal pillar sizes and etc.). On the basis, the analytic hierarchy process is used to build the judgment matrix and obtain the weight of each influencing factor. The results indicate that the overlying strata thickness, aquiclude and effective mining height are the most important factors among the primary factors of engineering and geological conditions, hydrogeological conditions and mining methods, respectively. The research results could provide theoretical references for the water-conserving mining of coal resources in northwest China.

Background: Acute kidney injury (AKI) is a common complication after surgery. Because of unpredictable and variable age-dependent physical decline, the incidence, risk factor of postsurgical AKI and the predictive power of estimated glomerular filtration rate prior to surgery (eGFRpreSurg) has not been fully elucidated in very elderly patients. Methods: All discharged patients aged ≥80 years without chronic kidney disease who underwent surgery prior to intensive care unit (ICU) admission from 2017 through 2018 were included. Clinical, biological and surgical data were recorded. Mean of outpatient creatinine values from the year prior to ICU admission was used as the baseline value to determine the occurrence of AKI. Postoperative AKI was diagnosed according to Kidney Disease Improving Global Outcomes criteria. Results: Among 243 very elderly postoperative patients admitted during the study period, 48 had AKI during their ICU stay. The occurrence of postsurgical AKI was associated with longer ventilation times (p

The exploitation and utilization of coal resources are not only prone to causing water table lowering, but also produce a large amount of CO2 and coal-based solid waste. A scientific concept that employs the CO2 and solid wastes to develop filling bodies and inject them into the mined-out area, to sequestrate CO2 and mitigate the overburden migration and thus preserve the overlying aquifer, is proposed. Continuous extraction and continuous backfill (CECB) mining was selected as the mining method to meet the aforementioned objectives. Additionally, carbon dioxide mineralized filling body (CMFB) under ambient temperature and pressure was developed, with fly ash as aggregate, and CO2 gas, silicate additives and cement as accessories. The uniaxial compressive strength (UCS) and tensile strength of CMFB with various curing times and fly ash contents were tested indoors. A physical analogue simulation and FLAC3D numerical calculation were then successively implemented on the premise of determining a similar material ratio of CMFB in analogue simulation and calibrating the parameters of the CMFB in numerical simulation. The deformation of aquifuge and water level lowering while using CECB and CMFB with various proportion of fly ash were obtained. When using the CMFB with 75% fly ash content and 28 d curing time, the maximum values of vertical displacement, horizontal displacement, inclination, horizontal deformation and curvature of aquiclude were 26 mm, 6.5 mm, 0.12 mm/m, 0.08 mm/m and 0.0015 mm/m2, respectively, and the water table decreased 0.47 m. The results show that the CMFB with 75% fly ash is the most appropriate ratio to realize water preservation mining, CO2 sequestration and harmless treatment of solid wastes, contributing to the green and sustainable development of coal areas.

Sepsis is more common among males than females, and the unequal estrogen levels have been suspected to play a vital role in gender differences. Recently, trained immunity is reported to be a novel strategy for the innate immune system to fight infection. However, it has not been clarified whether β-glucan-induced trained immunity causes different responses to early sepsis between male and female mice. In this study, sepsis was induced in mice by intraperitoneal injection of Escherichia coli (E. coli). The changes of inflammatory cytokines expression, and macrophage polarization in male, female, and ovariectomized C57BL/6 mice in sepsis model were investigated. For in vitro studies, different macrophages were treated with LPS. The function of estradiol (E2) on macrophage cell lines was verified and the mechanism of E2 affecting trained immunity was explored. We demonstrated that β-glucan-induced trained immunity was more resistant to sepsis in female than male mice. Macrophage polarization toward the M1 phenotype, which exhibited enhanced trained immunity, was related to the difference in sepsis resistance between female and male mice. Moreover, ovariectomized (OVX) mice manifested serious sepsis consequences with a weaker trained immunity effect than female mice. Female bone marrow-derived macrophages (BMDMs) were also apt to be polarized to the M1 phenotype in response to trained immunity in vitro. Furthermore, E2 promoted trained immunity in macrophage cell lines J774 and RAW264.7. E2 was also verified to facilitate trained immunity in primary BMDMs from female and male mice. Mechanistically, we found that E2 inhibited the nuclear translocation of RelB, which is a member of non-canonical pathway of NFκB and contributes to macrophage polarization to change the intensity of trained immunity. This study is the first to indicate the role of E2 in the trained immunity induced by β-glucan to protect against E. coli-induced sepsis via the non-canonical NFκB pathway. These results improve our understanding of the molecular mechanisms governing trained immunity in gender differences.

To prevent the pollution generated during charcoal roasting of tamarix lamb, environmental-friendly electric is gradually applied in meat processing. The profile and formation of flavor in roasted tamarix lamb were evaluated using HS-SPME/GC-MS combined with E-nose/-tongue. Results indicated that charcoal-roasted tamarix lamb exhibited the higher taste of umami and sourness in E-tongue and had higher contents of alcohols, aldehydes, ketones, alkanes, and aromatics in E-nose, while the electric ones exhibited the higher taste of sweetness and bitterness and had higher contents of nitrogen oxides, terpenes, aromatics, and organic sulfur. Compared with charcoal, application of the electric significantly decreased the numbers of key volatile compounds with VIP > 1 (markers) and the contents of most markers.

This paper provides an alternative lens of viewing digital technologies and networked spaces in outdoor intercultural learning, by introducing the Taoist philosophy of Ziran (nature) and Wuwei (inaction). The application of digital technology to outdoor learning has become prevailing and triggered critical debates and discussions among scholars and practitioners. The majority of the perspectives are, however, oriented in Western ideologies, and very rarely has any research considered this issue in the context of outdoor intercultural learning. A mini-ethnographic study was conducted to reconcile the nature-technology dichotomy during an EU-exchange sail-training voyage. Methodological implications are provided for conducting fieldwork in outdoor learning research, in line with the Ziran-Wuwei principles. The findings suggest that educators and facilitators follow the dialectical, relational, and contextual orientations to manage the (non)use of digital devices to maximise learners' outdoor experiential engagement and reflections.

Nang roasting is a traditional lamb processing method in Xinjiang (China) with a history of thousands of years. This study comprehensively evaluated the volatile and nonvolatile compounds of oyster cuts of roasted lamb at different processing stages of Nang roasting using gas chromatography mass spectrometry and amino acid automatic analyzer, respectively. Results indicated that aldehydes were the dominant profiles of volatile compounds, and hexanal, nonanal, octanal, (E)-2-nonenal, (E, E)-2,4-decadienal, (E, E)-2,4-nonadienal and 1-octen-3-ol were the key volatile compounds or aroma contributors to roasted oyster cuts. Isoamylol and 3-hydroxy-2-butanone could differentiate fresh and marinated oyster cuts from roasted ones; (E)-2-nonenal, (E, E)-2,4-decadienal, 1-octen-3-ol, hexanal, octanal, nonanal and (E, E)-2,4-nonadienal could differentiate Nang roasted oyster cuts of 60 min from those of 15, 30 and 45 min. Umami amino acids and sweet amino acids are the dominant profiles of nonvolatile compounds; glutamic acid, alanine and 5′-IMP were the key free amino acids or taste contributors to roasted oyster cuts. Glutamic acid, alanine and 5′-IMP could differentiate fresh and marinated oyster cuts from roasted samples. This work provided theoretical support for the control of flavor attributes of roasted lamb with traditional Nang roasting.

Static heterojunction-based electronic devices have been widely applied because carrier dynamic processes between semiconductors can be designed through band gap engineering. Herein, we demonstrate a tunable direct-current generator based on the dynamic heterojunction, whose mechanism is based on breaking the symmetry of drift and diffusion currents and rebounding hot carrier transport in dynamic heterojunctions. Furthermore, the output voltage can be delicately adjusted and enhanced with the interface energy level engineering of inserting dielectric layers. Under the ultrahigh interface electric field, hot electrons will still transfer across the interface through the tunneling and hopping effect. In particular, the intrinsic anisotropy of black phosphorus arising from the lattice structure produces extraordinary electronic, transport, and mechanical properties exploited in our dynamic heterojunction generator. Herein, the voltage of 6.1 V, current density of 124.0 A/m2, power density of 201.0 W/m2, and energy-conversion efficiency of 31.4% have been achieved based on the dynamic black phosphorus/AlN/Si heterojunction, which can be used to directly and synchronously light up light-emitting diodes. This direct-current generator has the potential to convert ubiquitous mechanical energy into electric energy and is a promising candidate for novel portable and miniaturized power sources in the in situ energy acquisition field.

To better protect the ecological environment during large scale underground coal mining operations in the northwest of China, the authors have proposed a water-conservation coal mining (WCCM) method. This case study demonstrated the successful application of WCCM in the Yu-Shen mining area. Firstly, by using the analytic hierarchy process (AHP), the influencing factors of WCCM were identified and the identification model with a multilevel structure was developed, to determine the weight of each influencing factor. Based on this, the five maps: overburden thickness contour, stratigraphic structure map, water-rich zoning map of aquifers, aquiclude thickness contour and coal seam thickness contour, were analyzed and determined. This formed the basis for studying WCCM in the mining area. Using the geological conditions of the Yu-Shen mining area, the features of caved zone, water conductive fractured zone (WCFZ) and protective zone were studied. The equations for calculating the height of the “three zones” were proposed. Considering the hydrogeological condition of Yu-Shen mining area, the criteria were put forward to evaluate the impact of coal mining on groundwater, which were then used to determine the distribution of different impact levels. Using strata control theory, the mechanism and applicability of WCCM methods, including height-restricted mining, (partial) backfill mining and narrow strip mining, together with the applicable zone of these methods, were analyzed and identified. Under the guidance of “two zoning” (zoning based on coal mining’s impact level on groundwater and zoning based on applicability of WCCM methods), the WCCM practice was carried out in Yu-Shen mining area. The research findings will provide theoretical and practical instruction for the WCCM in the northwest mining area of China, which is important to reduce the impact of mining on surface and groundwater.

Hypertriglyceridaemia is one of the most common causes of severe acute pancreatitis (SAP). However, the association between elevated triglycerides (TG) level in hospital stay and outcome in SAP patients with normal TG level at admission has not been clearly demonstrated. This retrospective study assessed the serum TG levels of patients with SAP admitted to the intensive care unit (ICU) in 2017. Variables with a statistically significant association with the incidence of in-hospital TG elevation, as determined by univariate analysis, were analysed using a logistic regression model to predictors. Of the 99 patients included in the study, TG levels were within the normal range in 59 (59.59%) patients at admission. Among patients with normal TG level when admitted to ICU, 28 (47.46%) experienced at least one episode of TG level elevation during their ICU stay. Elevated TG level in hospitalization is associated with an increased length of ICU stay, as well as increased mortality. In addition to other factors, propofol usage was independently associated with the occurrence of in-hospital-TG elevation. To conclude, we retrospectively investigated the incidence, outcome, and risk factors for in-hospital TG elevation events in SAP patients admitted to the ICU. We found a high incidence of both preexisting and in-hospital-acquired TG elevation in SAP patients admitted to the ICU. The TG elevation that occurred during the ICU stay was associated with worse outcomes and long-term hospitalization of the ICU. Propofol usage was independently associated with the TG elevation occurrence in the ICU.

BACKGROUND: Genetic architecture of coronary artery disease (CAD) is still to be defined. Since low density lipoprotein receptor-related protein 6 (LRP6) gene play critical roles in Wnt signal transduction which are important for vascular development and endodermis specification, we therefore resequenced it to search for mutations in CAD patients. METHODS: We systemically sequenced all the exons and promoter region of LRP6 gene in a sample of 380 early onset CAD patients and 380 control subjects in Chinese. RESULTS: In total, we identified 5 patient-specific mutations including K82N (two patients), S488Y (one patient), P1066T (two patients), P1206H (two patients) and I1264V (one patient) All these mutations located at the extracellular domain of LRP6 gene. In vitro functional analysis of patient-specific mutations demonstrated that these mutations resulted in a significant reduction in both protein level transporting to cell membrane and downstream Wnt signal activity. Furthermore, we found that LRP6 novel mutations attenuated proliferation and migration of human umbilical vein endothelial cells (HUVECs) when compared with wild type (WT) LRP6. CONCLUSION: Our results demonstrated that these loss-of-function variants might contribute to disease liability in a subset of CAD and defects in Wnt signal activation might be important contributing factors for the onset of CAD.

Mutations in the genes low-density lipoprotein (LDL) receptor-related protein-6 (LRP6) and myocyte enhancer factor 2A (MEF2A) were reported in families with coronary artery disease (CAD). We intend to determine the mutational spectrum of these genes among hyperlipidemic and normolipidemic CAD families. Forty probands with early-onset CAD were recruited from 19 hyperlipidemic and 21 normolipidemic Chinese families. We sequenced all exons and intron-exon boundaries of LRP6 and MEF2A, and found a novel heterozygous variant in LRP6 from a proband with normolipidemic CAD. This variant led to a substitution of histidine to tyrosine (Y418H) in an evolutionarily conserved domain YWTD in exon 6 and was not found in 1025 unrelated healthy individuals. Co-segregated with CAD in the affected family, LRP6Y418H significantly debilitated the Wnt3a-associated signaling pathway, suppressed endothelial cell proliferation and migration, and decreased anti-apoptotic ability. However, it exhibited no influences on low-density lipoprotein cholesterol uptake. Thus, mutation Y418H in LRP6 likely contributes to normolipidemic familial CAD via impairing endothelial cell functions and weakening the Wnt3a signaling pathway.

BackgroundRecent genome-wide association studies (GWAS) have mapped several novel loci influencing blood lipid levels in Caucasians. We sought to explore whether the genetic variants at newly identified lipid-associated loci were associated with CHD susceptibility in a Chinese Han population.Methodology/principal findingsWe conducted a two-stage case-control study in a Chinese Han population. The first-stage, consisting of 1,376 CHD cases and 1,376 sex and age- frequency matched controls, examined 5 novel lipid-associated single-nucleotide polymorphisms (SNPs) identified from GWAS among Caucasians in relation to CHD risk in Chinese. We then validated significant SNPs in the second-stage, consisting of 1,269 cases and 2,745 controls. We also tested associations between SNPs within the five novel loci and blood lipid levels in 4,121 controls. We identified two novel SNPs (rs599839 in CELSR2-PSRC1-SORT1 and rs16996148 in NCAN-CILP2) that were significantly associated with reduced CHD risk in Chinese (odds ratios (95% confidence intervals) in the dominant model 0.76 (0.61-0.90; P = 0.001), 0.67 (0.57-0.77; P = 3.4×10(-8)), respectively). Multiple linear regression analyses using dominant model showed that rs599839 was significantly associated with decreased LDL levels (P = 0.022) and rs16996148 was significantly associated with increased LDL and HDL levels (P = 2.9×10(-4) and 0.001, respectively).Conclusions/significanceWe identified two novel SNPs (rs599839 and rs16996148) at newly identified lipid-associated loci that were significantly associated with CHD susceptibility in a Chinese Han population.