Multiple myeloma is a malignant plasma-cell disease, which is highly dependent on the hypoxic bone marrow microenvironment. However, the underlying mechanisms of hypoxia contributing to myeloma ...genesis are not fully understood. Here, we show that long non-coding RNA DARS-AS1 in myeloma is directly upregulated by hypoxia inducible factor (HIF)-1. Importantly, DARS-AS1 is required for the survival and tumorigenesis of myeloma cells both
and
DARS-AS1 exerts its function by binding RNA-binding motif protein 39 (RBM39), which impedes the interaction between RBM39 and its E3 ubiquitin ligase RNF147, and prevents RBM39 from degradation. The overexpression of RBM39 observed in myeloma cells is associated with poor prognosis. Furthermore, knockdown of DARS-AS1 inhibits the mammalian target of rapamycin signaling pathway, an effect that is reversed by RBM39 overexpression. We reveal that a novel HIF-1/DARS-AS1/RBM39 pathway is implicated in the pathogenesis of myeloma. Targeting DARS-AS1/RBM39 may, therefore, represent a novel strategy to combat myeloma.
In recent years, the rapid expansion and development of the shale gas industry in the Sichuan Basin has coincided with a series of unexpected moderate-sized earthquakes. Given that the Sichuan Basin ...is situated within a stable interior block, the focal mechanism of the 2019 earthquake sequence (ML4.7, ML5.4, and ML5.2) in the Weiyuan-Rongxian area remains a subject of debate. In this study, we propose a joint InSAR- and PCA- based inversion method utilizing the distributed Mogi model to investigate the spatial-temporal characteristics of a gas reservoir and evaluate the induced Coulomb stress change. The surface deformation derived from Sentinel-1 data between 2015 and 2021 was consistent with the spatial distribution of production wells, and it correlated with the temporal changes in reservoir volume associated with the shale gas operating process. The Coulomb stress loading on the regional faults suggests that human activities associated with shale gas operation likely triggered the three moderate earthquakes. Furthermore, our results indicate Coulomb stress loadings of 10 kPa, 15 kPa, 5 kPa, 3 kPa, and 87 kPa on the Dongxingchang fault, Gaoqiao fault, Dayaokou fault, Niujingao fault, and Lijiachang fold, respectively. Consequently, fluid injection and extraction during shale gas development could be contributing to the elevated seismic activity in the Weiyuan-Rongxian area.
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•Expression of some GRGs was significantly associated with the prognosis or progression of pancreatic cancer.•Pancreatic cancer cell death was enhanced following inhibition of ...glycolysis.•The sensitivity of cancer cells to GEM was elevated by 2-DG.•A prognostic model involving GRGs should be helpful for pancreatic cancer early diagnosis and treatment.
Previous studies have reported that increased glycolytic activity enhances chemotherapy resistance in some types of malignancies. However, whether glycolysis influences the curative effect of gemcitabine (GEM) on pancreatic cancer (PC) cells remains unclear. The aim of this study was to investigate the status of glycolysis in PC and its association with tolerance to GEM. Data from The Cancer Genome Atlas (TCGA) were used to analyze the correlation between glycolysis-related gene (GRG) expression and PC progression and prognosis. 2-Deoxy-D-glucose (2-DG) was applied to assess the effect of glycolysis inhibition on PC cell death and GEM tolerance. Expression of some GRGs, such as HK1, GAPDH, PKM2, and LDHA, was significantly associated with the prognosis of PC. Furthermore, HK1, PKLR, and LDHA expression correlated positively with PC progression. Further analysis revealed that cancer cell death was markedly enhanced following glycolysis inhibition and that the sensitivity of cancer cells to GEM was notably increased in the presence of 2-DG. Our findings indicate that abnormally increased glycolytic activity promotes the development of PC and enhances drug tolerance to GEM. 2-DG combined with GEM is a potential therapy for PC.
The 2021 Mw 7.4 Maduo earthquake occurred in the north-central Bayan Har block, which has been the most seismically active block of the Tibetan Plateau during recent decades. The Maduo earthquake ...provides an opportunity to study the rupture kinematics and seismogenic environment associated with subsidiary faults inside the block. We investigate the source rupture process of the Maduo earthquake by combining the seismological analyses and the joint inversion of geodetic and seismic data. We find that the source rupture propagates bilaterally on a splay fault geometry consisting of two steeply dipping segments. The slip distribution is dominated by sinistral slips and contains several asperities. The maximum slip is approximately 4.2 m, and the rupture duration is about 40 s. The spatiotemporal evolution of Coulomb failure stress (CFS) changes on the fault demonstrates the interactions of stress triggering between multiple asperities, indicating the cascading rupture process of the Maduo earthquake. Moreover, this event produces significant CFS increases on the subsidiary faults of the Bayan Har block, among which the Maduo-Gande and Tibet Dagou-Changmahe faults receive the largest stress loading. The occurrences of the 1947 Dari and 2021 Maduo earthquakes suggest that the seismic hazard of the subsidiary faults should not be neglected. Because the CFS on the Tuosuo Lake and Maqin-Maqu segments of the East Kunlun fault is also increased, the enhanced seismic hazard deserves further attention. In addition, the slip distribution illustrates that the source rupture is mainly concentrated in the brittle upper crust. We propose that the Maduo earthquake arises from the continuous loading on the internal fault of the Bayan Har block caused by the collision between the Eurasian and Indian plates, and the eastward extrusion of the middle-to-lower crustal flow facilitates the occurrence of this event. These factors constitute the seismogenic environment of the Maduo earthquake.
•A branch fault geometry consisting of two steeply dipping segments.•A finite-fault joint inversion combining seismic and geodetic data.•A bilateral rupture dominated by sinistral slips with multiple asperities.•Significant static Coulomb failure stress increases on surrounding active faults.
Precisely imitating human motions in real-time poses a challenge for the robots due to difference in their physical structures. This paper proposes a human-computer interaction method for remotely ...manipulating life-size humanoid robots with a new metrics for evaluating motion similarity. First, we establish a motion capture system to acquire the operator's motion data and retarget it to the standard bone model. Secondly, we develop a fast mapping algorithm, by mapping the BVH (BioVision Hierarchy) data collected by the motion capture system to each joint motion angle of the robot to realize the imitated motion control of the humanoid robot. Thirdly, a DTW (Dynamic Time Warping)-based trajectory evaluation method is proposed to quantitatively evaluate the difference between robot trajectory and human motion, and meanwhile, visualization terminals render it more convenient to make comparisons between two different but simultaneous motion systems. We design a complex gesture simulation experiment to verify the feasibility and real-time performance of the control method. The proposed human-in-the-loop imitation control method addresses a prominent non-isostructural retargeting problem between human and robot, enhances robot interaction capability in a more natural way, and improves robot adaptability to uncertain and dynamic environments.
The 8 January 2022 Mw6.7 Menyuan earthquake was generated in the transition zone between the western Lenglongling fault and the eastern Tuolaishan fault, both being part of the Qilian–Haiyuan fault ...system with an important role in the adjustment of the regional tectonic regime. In this study, four pairs of SAR (synthetic aperture radar) data from Sentinel-1 and ALOS-2 (Advanced Land Observation Satellite-2) satellites were used to derive the surface displacement observations along the satellite line-of-sight (LOS) and azimuth directions using the differential interferometric SAR (InSAR, DInSAR), pixel offset-tracking (POT), multiple aperture InSAR (MAI), and burst overlap InSAR (BOI) methods. An SM-VCE method (i.e., a method for measuring three-dimensional (3D) surface displacements with InSAR based on a strain model and variance component estimation) was employed to combine these derived SAR displacement observations to calculate the 3D co-seismic displacements. Results indicate that the 2022 Menyuan earthquake was dominated by left-lateral slip, and the maximum horizontal and vertical displacements were 1.9 m and 0.6 m, respectively. The relative horizontal surface displacement across the fault was as large as 2–3 m, and the fault-parallel displacement magnitude was larger on the southern side of the fault compared with the northern side. Furthermore, three co-seismic strain invariants were also investigated, revealing that the near-fault area suffered severe deformation, and two obviously expanding and compressed zones were identified. We provide displacements/strains derived in this study in the prevailing geotiff format, which will be useful for the broad community studying this earthquake; in addition, the SM-VCE code used in this study is open to the public so that readers can better understand the method.
Understanding the relationship between climatic conditions and dune ecosystems requires the large-scale monitoring of spatiotemporal patterns of dune velocities. Due to their large extent and ...remoteness, dune fields are ideal for remote sensing techniques. Dune velocities in the Sand Sea North Sinai are characterized by large spatial and temporal variability. To this end, a total of 265 pairs from four Landsat-8 images from April 2013 to April 2018 were automatically matched with the COSI Corr engine to determine the dune velocities. These pairs were selected so that differences in the solar angles were small and spanned at least one year. This helps to reduce shadowing in the deformation fields and the error budget in converting displacements to annual velocities. To improve spatial coverage and reduce measurement uncertainty, the fusion of individual offset maps is considered feasible. We compared the performance of two methods (i.e., inversion and temporal median fusion) in performing the fusion of individual velocities, and the two methods showed good agreement. The fusion of individual velocities allowed us to estimate the final velocities for about 98.8% of the dune areas. Our results suggest that the magnitudes and directions of dune migration at Sand Sea are spatially and temporally variable. The geometric mean of the active features associated with 12 regions in the Sand Sea ranged from 1.65 m/y to 3.52 m/y, with median directions from 56.19° to 173.11°. The stable regions allowed us to estimate the 95% confidence intervals of the final velocities and extend these calculations to the dune targets. The median uncertainties were 0.10 m/y and 0.25 m/y for the stable and moving targets, respectively. We estimated the coherence of the final velocity vector, which can be considered as an indicator of the homogeneity of migration directions between the offset maps. We compared the final Landsat-8 velocities with those from Sentinel-2 to validate the results and found a good agreement in the magnitudes and directions. The process of selecting high-quality pairs and then fusing the individual maps showed a high performance in terms of spatial coverage and reliability of the extracted velocities.
This study aimed to investigate the effects of quercetin on the efficacy of various chemotherapeutic drugs in cervical cancer cells.
All drug experiments were performed in HeLa and SiHa cells. The ...cell viability was detected by Cell Counting Kit-8 assay, and cell proliferation was estimated by bromodeoxyuridine assay. CompuSyn software was utilized to calculate the combination index (CI) and evaluate the synergistic or antagonistic effect of quercetin with cisplatin, paclitaxel, 5-fluorouracil and doxorubicin on cell viability. Cell migration and invasion abilities were detected by transwell assays, and cell apoptosis was measured by flow cytometry. The expression levels of matrix metallopeptidase 2 (MMP2), ezrin, P-glycoprotein (P-Gp) and methyltransferase-like 3 (METTL3) protein treated with various drugs were analyzed by Western blotting.
Quercetin inhibited the viability of HeLa and SiHa cells in a dose- and time-dependent manner. The CI values of quercetin with cisplatin, paclitaxel, 5-fluorouracil and doxorubicin were <1, >1, >1 and >1, respectively. The effect of combination of quercetin and cisplatin on cell proliferation was stronger than their individual effects. Co-treatment group could inhibit more cell migration and invasion in contrast to single-drug group. Besides, quercetin combined with cisplatin group induced more cell apoptosis in contrast to single-drug group. The results of Western blotting showed that the expression levels of MMP2, ezrin, P-Gp and METTL3 in co-treatment group were lower than in cisplatin group, respectively.
Quercetin and cisplatin had synergistic inhibitory effect on cervical cancer cells. Quercetin might enhance the antitumor effect of cisplatin via inhibiting proliferation, migration and invasion and elevating apoptosis through weakening MMP2, ezrin, METTL3 and P-Gp expression of cancer cells.
The demand for waterproof leather has been increasing, and environmentally friendly waterproof fatliquors have recently received increasing attention. In this work, two polymer nanoemulsions ...containing carboxyl groups were synthesized and used as waterproof fatliquors for chrome-tanned leather. First, a reactive emulsifier (C
-Na) was prepared using itaconic anhydride and lauryl alcohol. Subsequently, two polymer nanoemulsions were prepared through mini-emulsion polymerization with C
-Na as the emulsifier, 4,4'-azobis (4-cyanovaleric acid) as the initiator, and lauryl acrylate (LA)/stearyl acrylate (SA) as monomers; these were named PLA and PSA. PLA and PSA were characterized using FT-IR, a Zetasizer, and GPC. It was found that the critical micellar concentration (CMC) of C
-Na was 2.34 mmol/L, which could reduce the surface tension of water to 26.61 mN/m. The average particle sizes of PLA and PSA were 53.39 and 67.90 nm, respectively. The maeser flexes of leather treated with PLA and PSA were 13928 and 19492 at a 5% dosage, respectively, and the contact angles reached 148.4° and 150.3°, respectively; these values were both higher than for a conventional fatliquor. Compared with PLA, the leather treated with PSA exhibited better fullness, and tensile and tearing strength. The prepared nanoemulsions have prospective applications in leather manufacturing as waterproof fatliquors.
Industrial waste salt is classified as hazardous waste to the environment. The organic impurity and its occurrence in industrial waste salt affect the salt resource utilization. In this paper, ...composition quantitative analysis, XRD, TG-DSC, SEM/FIB-SEM coupled with EDS, FTIR, XPS and GC-Ms were chosen to investigate the organic impurity and its occurrence in industrial waste salt. The organic impurities owe small proportion (1.77%) in the specimen and exhibit weak thermal stability within the temperature of 600°C. A clear definition of organic impurity, including 11 kinds of organic compounds, including aldehyde, benzene and its derivatives etc., were detected in the industrial waste salt. These organic impurities, owing (C-O/C-O-C, C-OH/C = O, C-C/CHx/C = C etc.)-containing function group substance, are mainly distributed both on the surface and inside of the salt particles. Meanwhile, the organic substance may combine with metal cations (Ni2+, Mg2+, Cu2+ etc.) through functional groups, such as hydroxide, carbonyl etc., which increases its stability in the industrial waste salt. These findings provide comprehensive information for the resource utilization of industrial waste salt from chemical industry etc.
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