Reactive oxygen species (ROS) are produced by living cells as normal cellular metabolic byproduct. Under excessive stress conditions, cells will produce numerous ROS, and the living organisms ...eventually evolve series of response mechanisms to adapt to the ROS exposure as well as utilize it as the signaling molecules. ROS molecules would trigger oxidative stress in a feedback mechanism involving many biological processes, such as apoptosis, necrosis and autophagy. Growing evidences have suggested that ROS play a critical role as the signaling molecules throughout the entire cell death pathway. Overwhelming production of ROS can destroy organelles structure and bio-molecules, which lead to inflammatory response that is a known underpinning mechanism for the development of diabetes and cancer. Cytochrome P450 enzymes (CYP) are regarded as the markers of oxidative stress, can transform toxic metabolites into ROS, such as superoxide anion, hydrogen peroxide and hydroxyl radical which might cause injury of cells. Accordingly, cells have evolved a balanced system to neutralize the extra ROS, namely antioxidant systems that consist of enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidases (GPxs), thioredoxin (Trx) as well as the non-enzymatic antioxidants which collectively reduce oxidative state. Herein, we review the recent novel findings of cellular processes induced by ROS, and summarize the roles of cellular endogenous antioxidant systems as well as natural anti-oxidative compounds in several human diseases caused by ROS in order to illustrate the vital role of antioxidants in prevention against oxidative stress.
Low-loss photonic integrated circuits and microresonators have enabled a wide range of applications, such as narrow-linewidth lasers and chip-scale frequency combs. To translate these into a ...widespread technology, attaining ultralow optical losses with established foundry manufacturing is critical. Recent advances in integrated Si
N
photonics have shown that ultralow-loss, dispersion-engineered microresonators with quality factors Q > 10 × 10
can be attained at die-level throughput. Yet, current fabrication techniques do not have sufficiently high yield and performance for existing and emerging applications, such as integrated travelling-wave parametric amplifiers that require meter-long photonic circuits. Here we demonstrate a fabrication technology that meets all requirements on wafer-level yield, performance and length scale. Photonic microresonators with a mean Q factor exceeding 30 × 10
, corresponding to 1.0 dB m
optical loss, are obtained over full 4-inch wafers, as determined from a statistical analysis of tens of thousands of optical resonances, and confirmed via cavity ringdown with 19 ns photon storage time. The process operates over large areas with high yield, enabling 1-meter-long spiral waveguides with 2.4 dB m
loss in dies of only 5 × 5 mm
size. Using a response measurement self-calibrated via the Kerr nonlinearity, we reveal that the intrinsic absorption-limited Q factor of our Si
N
microresonators can exceed 2 × 10
. This absorption loss is sufficiently low such that the Kerr nonlinearity dominates the microresonator's response even in the audio frequency band. Transferring this Si
N
technology to commercial foundries can significantly improve the performance and capabilities of integrated photonics.
Direct cross-coupling between simple arenes and heterocyclic amines under mild conditions is undoubtedly important for C-N bonds construction. Selective C(sp
)-H amination is more valuable. Herein we ...show a selective C(sp
)-H amination of arenes (alkyl-substituted benzenes, biphenyl and anisole derivatives) accompanied by hydrogen evolution by using heterocyclic azoles as nitrogen sources. The reaction is selective for C(sp
)-H bonds, providing a mild route to N-arylazoles. The KIE (kinetic isotope effect) experiment reveals the cleavage of C-H bond is not involved in the rate-determining step. Kinetic studies indicate the first-order behaviour with respect to the arene component. It is interesting that this system works without the need for any sacrificial oxidant and is highly selective for C(sp
)-H activation, whereas C(sp
)-H bonds are unaffected. This study may have significant implications for the functionalization of methylarenes which are sensitive to oxidative conditions.
In this paper, we proposed a multi-sensor integrated navigation system composed of GNSS (global navigation satellite system), IMU (inertial measurement unit), odometer (ODO), and LiDAR (light ...detection and ranging)-SLAM (simultaneous localization and mapping). The dead reckoning results were obtained using IMU/ODO in the front-end. The graph optimization was used to fuse the GNSS position, IMU/ODO pre-integration results, and the relative position and relative attitude from LiDAR-SLAM to obtain the final navigation results in the back-end. The odometer information is introduced in the pre-integration algorithm to mitigate the large drift rate of the IMU. The sliding window method was also adopted to avoid the increasing parameter numbers of the graph optimization. Land vehicle tests were conducted in both open-sky areas and tunnel cases. The tests showed that the proposed navigation system can effectually improve accuracy and robustness of navigation. During the navigation drift evaluation of the mimic two-minute GNSS outages, compared to the conventional GNSS/INS (inertial navigation system)/ODO integration, the root mean square (RMS) of the maximum position drift errors during outages in the proposed navigation system were reduced by 62.8%, 72.3%, and 52.1%, along the north, east, and height, respectively. Moreover, the yaw error was reduced by 62.1%. Furthermore, compared to the GNSS/IMU/LiDAR-SLAM integration navigation system, the assistance of the odometer and non-holonomic constraint reduced vertical error by 72.3%. The test in the real tunnel case shows that in weak environmental feature areas where the LiDAR-SLAM can barely work, the assistance of the odometer in the pre-integration is critical and can effectually reduce the positioning drift along the forward direction and maintain the SLAM in the short-term. Therefore, the proposed GNSS/IMU/ODO/LiDAR-SLAM integrated navigation system can effectually fuse the information from multiple sources to maintain the SLAM process and significantly mitigate navigation error, especially in harsh areas where the GNSS signal is severely degraded and environmental features are insufficient for LiDAR-SLAM.
Tumor cells reside in a highly complex and heterogeneous tumor microenvironment (TME), which is composed of a myriad of genetically stable non-cancer cells, including fibroblasts, immune cells, ...endothelial cells, and epithelial cells, and a tumor-specific extracellular matrix (ECM). Cancer-associated fibroblasts (CAFs), as an abundant and active stromal cell population in the TME, function as the signaling center and remodeling machine to aid the creation of a desmoplastic tumor niche. Although there is no denial that the TME and CAFs may have anti-tumor effects as well, a great deal of findings reported in recent years have convincingly revealed the tumor-promoting effects of CAFs and CAF-derived ECM proteins, enzymes, chemical factors and other downstream effectors. While there is growing enthusiasm for the development of CAF-targeting therapies, a better understanding of the complexities of CAF-ECM and CAF-cancer cell interactions is necessary before novel therapeutic strategies targeting the malignant tumor "soil" can be successfully implemented in the clinic.
•High intensity ultrasound technology was used to modify soy protein isolate-pectin.•The fluorescence intensity increased by high intensity ultrasound treatment.•The particle size of the complex ...reduced by high intensity ultrasound treatment.•The structural properties and solubility of protein were improved at 450 W for 15 min.
In this study, a soy protein isolate (SPI)-pectin (PC) complex was prepared, and the effects of different high intensity ultrasound (HIU) powers on the structure and solubility of the complex were studied. Fourier transform infrared (FTIR) spectroscopy analysis exhibited that with increasing HIU power, the α-helix content of the SPI in the complex was significantly reduced, and the random coil content increased; however, an opposite trend appeared after higher power treatments. Fluorescence spectra showed that HIU treatment increased the fluorescence intensity of the complex, and the surface hydrophobicity was increased. The trend of the protein structure studied by Raman spectroscopy was similar to that of FTIR and fluorescence spectroscopy. When the HIU treatment was performed for 15 min and at 450 W power, the particle size of the complex was 451.85 ± 2.17 nm, and the solubility was 89.04 ± 0.19 %, indicating that the HIU treatment caused the spatial conformation of the protein to loosen and improved the functional properties of the complex. Confocal laser scanning microscopy (CLSM) revealed that the complex after HIU treatment exhibited improved dispersibility in water and smaller particle size. Gel electrophoresis results indicated that HIU treatment did not affect the protein subunits of the complex. Therefore, the selection of a suitable HIU treatment power can effectively improve the structural properties and solubility of SPI in the complex, and promote the application of the SPI-PC complex in food processing and industries.
A Global Navigation Satellite System (GNSS)/Inertial Navigation System (INS)/Light Detection and Ranging (LiDAR)-Simultaneous Localization and Mapping (SLAM) integrated navigation system based on ...graph optimization is proposed and implemented in this paper. The navigation results are obtained by the information fusion of the GNSS position, Inertial Measurement Unit (IMU) preintegration result and the relative pose from the 3D probability map matching with graph optimizing. The sliding window method was adopted to ensure that the computational load of the graph optimization does not increase with time. Land vehicle tests were conducted, and the results show that the proposed GNSS/INS/LiDAR-SLAM integrated navigation system can effectively improve the navigation positioning accuracy compared to GNSS/INS and other current GNSS/INS/LiDAR methods. During the simulation of one-minute periods of GNSS outages, compared to the GNSS/INS integrated navigation system, the root mean square (RMS) of the position errors in the North and East directions of the proposed navigation system are reduced by approximately 82.2% and 79.6%, respectively, and the position error in the vertical direction and attitude errors are equivalent. Compared to the benchmark method of GNSS/INS/LiDAR-Google Cartographer, the RMS of the position errors in the North, East and vertical directions decrease by approximately 66.2%, 63.1% and 75.1%, respectively, and the RMS of the roll, pitch and yaw errors are reduced by approximately 89.5%, 92.9% and 88.5%, respectively. Furthermore, the relative position error during the GNSS outage periods is reduced to 0.26% of the travel distance for the proposed method. Therefore, the GNSS/INS/LiDAR-SLAM integrated navigation system proposed in this paper can effectively fuse the information of GNSS, IMU and LiDAR and can significantly mitigate the navigation error, especially for cases of GNSS signal attenuation or interruption.
Osteosarcomas are one of the most common primary malignant tumors of bone. It primarily occurs in children and adolescents, with the second highest incidence among people over 50 years old. Although ...there were immense improvements in the survival of patients with osteosarcoma in the past 30 years, targetable mutations and agents of osteosarcomas still have been generally not satisfactory. Therefore, it is of great importance to further explore the highly specialized immune environment of bone, genes related to macrophage infiltration and potential therapeutic biomarkers and targets.
The 11 expression data sets of OS tissues and the 11 data sets of adjacent non-tumorous tissues available in the GEO database GSE126209 were used to conduct immune infiltration analysis. Then, through WGCNA analysis, we acquired the co-expression modules related to Mast cells activated and performed the GO and KEGG enrichment analysis. Next, we did the survival prognosis analysis and plotted a survival curve. Finally, we analyzed the COX multivariate regression of gene expression on clinical parameters and drew forest maps for visualization by the forest plot package.
OS disease-related immune cell populations, mainly Mast cells activated, have higher cell content (p = 0.006) than the normal group. Then, we identified co-expression modules related to Mast cells activated. In sum, a total of 822 genes from the top three strongest positive correlation module MEbrown4, MEdarkslateblue and MEnavajowhite2 and the strongest negative correlation module MEdarkturquoise. From that, we identified nine genes with different levels in immune cell infiltration related to osteosarcoma, eight of which including SORBS2, BAIAP2L2, ATAD2, CYGB, PAMR1, PSIP1, SNAPC3 and ZDHHC21 in their low abundance have higher disease-free survival probability than the group in their high abundances.
These results could assist clinicians to select targets for immunotherapies and individualize treatment strategies for patients with OS.
The tumor stroma and its cellular components are known to play an important role in tumor response to treatment. Here, we report a novel resistance mechanism in melanoma that is elicited by BRAF ...inhibitor (BRAFi)-induced noncanonical activation of nuclear β-catenin signaling in cancer-associated fibroblasts (CAF). Treatment with BRAFi leads to an expanded CAF population with increased β-catenin nuclear accumulation and enhanced biological properties. This CAF subpopulation is essential for melanoma cells to proliferate and acquire resistance to BRAFi/MEK inhibitors (MEKi). Mechanistically, BRAFi induces BRAF-CRAF heterodimerization and subsequent activation of ERK signaling in CAFs, leading to inactivation of the β-catenin destruction complex. RNA-seq identified periostin (POSTN) as a major downstream effector of β-catenin in CAFs. POSTN compensates for the loss of β-catenin in CAFs and mediates melanoma cell BRAFi/MEKi resistance. In melanoma cells, POSTN activates phosphoinositide 3-kinase (PI3K)/AKT signaling and subsequently reactivates the ERK pathway that was inhibited by BRAFi/MEKi. Collectively, these data underscore the role of BRAFi-induced CAF reprogramming in matrix remodeling and therapeutic escape of melanoma cells. SIGNIFICANCE: β-Catenin activation in cancer-associated fibroblasts in response to BRAF inhibitors stimulates POSTN secretion to promote resistance in cancer cells, revealing POSTN as a potential matrix target in cancer therapy.
•A novel wet-mechanochemical pretreatment method was performed.•Small dosage dilute alkali assisted ball milling promoted biomass saccharification.•NaOH concentration showed significant positive ...correlation to reducing sugars yield.•Composition of lignocelluloses showed great impact on their saccharification.
Achieving the capacity to produce fermentable sugars from lignocelluloses via green and efficient approaches is of strategic significance to an environmentally sustainable society. In this work, a novel wet-mechanochemical pretreatment approach was proposed using small amount of dilute alkali-assisted ball milling and subsequently hydrothermal pretreatment at mild conditions to enhance the enzymatic saccharification efficiency of bagasse and pennisetum. Effects of pretreatment conditions, such as NaOH concentration, hydrothermal reaction temperature and time, on the reducing sugars production were systematically evaluated. Parameters were optimized by statistical analysis and response surface methodology. Results showed that the existence of small amount of dilute alkali during ball milling can greatly facilitate the subsequent saccharification of bagasse and pennisetum, which can reduce the alkali dosage in comparison with traditional biomass pretreatment approach. The highest reducing sugars yield of 40.75% could be obtained from bagasse after pretreated by final concentration of 0.4% alkali in hydrothermal pretreatment process at 100 °C for 40 min. 55.74% of reducing sugars could be obtained from pennisetum treated by final concentration of 0.4% alkali in hydrothermal pretreatment process at 80 °C for 60 min. Compared with pretreatment temperature and time, NaOH concentration had more impact on the reducing sugars yield. Chemical composition of lignocelluloses also showed great influences on their saccharification efficiency. This work provides feasible theoretical basis and method for the efficient utilization of lignocelluloses.
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