Rupture process of the 2021 M7.4 Maduo earthquake and implication for deformation mode of the Songpan-Ganzi terrane in Tibetan Plateau.

The deformation mode of the Tibetan Plateau is of crucial importance for understanding its construction and extrusion processes, as well as for the assessment of regional earthquake potential. Block motion and viscous flow models have been proposed to describe the deformation field but are not fully supported by modern geophysical observations. The 2021 Mw 7.4 Maduo earthquake, which occurred inside the Songpan-Ganzi terrane (SGT) in central-east Tibet, provides a chance to evaluate the associated deformation mode of the region. We conduct a joint inversion for this earthquake and resolve a bilateral rupture process, which is characterized by super- and subshear rupture velocities, respectively. We interpret this distinct rupture behavior to be the result of the respective slip concentration depths of the two ruptured segments. We analyze geological, seismic, and geodetic evidence and find that the SGT upper crust shows distributed shear deformation and distinct transverse anisotropy, which are associated with folded structures originating from compression of the paleo-Tethys ocean accretional prism realigned by following shear deformation. The SGT receives lateral shear loading from its NS boundary and accommodates a right-step sinistral motion across the terrane boundary faults. The unique tectonic setting of the SGT defines locations and behaviors of internal faulting and strong earthquakes such as the 2021 Maduo earthquake, with the latter occurring on slow-moving faults at intervals of several thousands of years.

Unveiling the PDK4-centered rituximab-resistant mechanism in DLBCL: the potential of the "Smart" exosome nanoparticle therapy.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) represents a prevalent malignant tumor, with approximately 40% of patients encountering treatment challenges or relapse attributed to rituximab resistance, primarily due to diminished or absent CD20 expression. Our prior research identified PDK4 as a key driver of rituximab resistance through its negative regulation of CD20 expression. Further investigation into PDK4's resistance mechanism and the development of advanced exosome nanoparticle complexes may unveil novel resistance targets and pave the way for innovative, effective treatment modalities for DLBCL. METHODS: We utilized a DLBCL-resistant cell line with high PDK4 expression (SU-DHL-2/R). We infected it with short hairpin RNA (shRNA) lentivirus for RNA sequencing, aiming to identify significantly downregulated mRNA in resistant cells. Techniques including immunofluorescence, immunohistochemistry, and Western blotting were employed to determine PDK4's localization and expression in resistant cells and its regulatory role in phosphorylation of Histone deacetylase 8 (HDAC8). Furthermore, we engineered advanced exosome nanoparticle complexes, aCD20@ExoCTX/siPDK4, through cellular, genetic, and chemical engineering methods. These nanoparticles underwent characterization via Dynamic Light Scattering (DLS) and Transmission Electron Microscopy (TEM), and their cellular uptake was assessed through flow cytometry. We evaluated the nanoparticles' effects on apoptosis in DLBCL-resistant cells and immune cells using CCK-8 assays and flow cytometry. Additionally, their capacity to counteract resistance and exert anti-tumor effects was tested in a resistant DLBCL mouse model. RESULTS: We found that PDK4 initiates HDAC8 activation by phosphorylating the Ser-39 site, suppressing CD20 protein expression through deacetylation. The aCD20@ExoCTX/siPDK4 nanoparticles served as effective intracellular delivery mechanisms for gene therapy and monoclonal antibodies, simultaneously inducing apoptosis in resistant DLBCL cells and triggering immunogenic cell death in tumor cells. This dual action effectively reversed the immunosuppressive tumor microenvironment, showcasing a synergistic therapeutic effect in a subcutaneous mouse tumor resistance model. CONCLUSIONS: This study demonstrates that PDK4 contributes to rituximab resistance in DLBCL by modulating CD20 expression via HDAC8 phosphorylation. The designed exosome nanoparticles effectively overcome this resistance by targeting the PDK4/HDAC8/CD20 pathway, representing a promising approach for drug delivery and treating patients with Rituximab-resistant DLBCL.

Role of ERß in the ovary and ovary related diseases.

Estrogen and estrogen receptors (ERα and ERß) regulate a multitude of complicated physiological and pathological processes. Jan-Ake Gustafsson's group discovered ERß in 1996, this crucial finding gives us new insights into the understanding of estrogen signaling. ERß is highly expressed in the ovary and particularly exists in granulosa cells (GCs). ERß is a key transcription factor in the maintenance of ovarian granulosa cell growth, differentiation, and homeostasis, and the ovulation function of ovarian follicles and oocytes. Additionally, ERß can modulate the steroidogenic transcriptional program through phosphorylation and regulate both gonadotropin response and FOXL2 expression within the ovary. In this review, we focus on the role of ERß in regulating ovarian granulosa cell development and homeostasis, particularly its significance in ovarian cancer (OC), premature ovarian failure (POF), and polycystic ovary syndrome (PCOS). It also highlights the prospects of small molecule compounds targeting ERß, providing a new strategy for the treatment of ovarian-related diseases.

Responsive Multi-Arm PEG-Modified COF Nanocomposites: Dynamic Photothermal, pH/ROS Dual-Responsive, Targeted Carriers for Rheumatoid Arthritis Treatment.

Rheumatoid arthritis (RA) is a chronic immune disease characterized by the infiltration of immune cells and the proliferation of fibroblast-like synoviocytes (FLS) at the joint site, leading to inflammation and joint destruction. However, the available treatment options targeting both inflammatory and proliferative FLS are limited. Herein, this work presents three covalent organic frameworks (COFs) photothermal composite systems modified with multi-armed polyethylene glycols (PEG) for the treatment of RA. These systems exhibit a dual response under low pH and high reactive oxygen species (ROS) conditions at the site of inflammation, with a specific focus on delivering the protein drug ribonuclease A (RNase A). Notably, molecular docking studies reveal the interaction between RNase A and NF-κB p65 protein, and Western blotting confirm its inhibitory effect on NF-κB activity. In vitro and in vivo experiments verify the significant reduction in joint swelling and deformities in adjuvant-induced arthritis (AIA) rats after treatment with RNase A delivered by multi-armed PEG-modified COF ligands, restoring joint morphology to normal. These findings underscore the promising therapeutic potential of COFs for the treatment of RA, highlighting their unique capabilities in addressing both inflammatory and proliferative aspects of the disease and expanding the scope of biomedical applications for COFs.

Southern Tibetan rifting since late Miocene enabled by basal shear of the underthrusting Indian lithosphere.

Syncontractional extension is prominent in present-day Tibet, but its origin remains vigorously debated. Several deep-seated geodynamic processes (e.g., Indian underthrusting, horizontal flow, and mantle upwelling) have been linked to Tibetan rifting. Indian underthrusting is a good candidate because it can well explain why surface rifts are more prominent south of the Bangong-Nujiang suture; however, how Indian underthrusting causes extension is not well understood and lacks observational constraints. Seismic anisotropy, measured by exploiting the birefringence effect of shear waves, can be indicative of the deformation styles within the crust. Here, we unveil the dominant convergence-parallel alignment of anisotropic fabrics in the deep crust of the southern Tibetan rifts using seismic recordings collected from our recently deployed and existing seismic stations. This finding suggests that the strong north-directed shearing exerted by the underthrusting Indian plate is key to enabling present-day extension in southern Tibet.

Voluminous continental growth of the Altaids and its control on metallogeny.

The Altaids is generally considered to be the largest Phanerozoic accretionary orogen on Earth, but it is unclear whether it was associated with extensive continental crustal growth and whether there is a link between the crustal growth and ore mineralization. This paper reviews whole-rock Nd and zircon Hf isotope data for felsic-intermediate-mafic igneous rocks in the Altaids and presents Nd + Hf isotopic contour maps for this region. The maps highlight the 3D lithospheric compositional architecture of the Altaids and make it possible to quantitatively evaluate the crustal growth and its relationship with ore deposits. The Altaids hosts ∼4 107 350 km2 and ∼184 830 750 km3 (assuming a crustal thickness of 40-50 km) juvenile crust (ϵ Nd(t) > 0), accounting for 58% by isotope-mapped area (∼7 010 375 km2) of almost all outcrops of the Altaids (∼8 745 000 km2) and formed during 1000-150 Ma (mainly 600-150 Ma). The juvenile crustal, slightly juvenile-reworked crustal and slightly reworked crustal provinces controlled the Cu-Au, the Pb-Zn-Ag and the Li-Be, Nb-Ta and W-Sn ore deposits. According to the crustal architecture and background of deep compositions, we propose that the ore deposits can be grouped into three types: juvenile crust-related, mixed-source (or slightly juvenile crust)-related and reworked crust-related. This highlights the close relationship between accretion, continental growth and mineralization, and will facilitate exploration for specific ore-deposit types in the Altaids.

Bridging the connection between effective viscosity and electrical conductivity through water content in the upper mantle.

Upper mantle viscosity plays a key role in understanding plate tectonics and is usually extrapolated from laboratory-based creep measurements of upper mantle conditions or constrained by modeling geodetic and post-seismic observations. At present, an effective method to obtain a high-resolution viscosity structure is still lacking. Recently, a promising estimation of effective viscosity was obtained from a transform derived from the results of magnetotelluric imaging. Here, we build a relationship between effective viscosity and electrical conductivity in the upper mantle using water content. The contribution of water content to the effective viscosity is isolated in a flow law with reference to relatively dry conditions in the upper mantle. The proposed transform is robust and has been verified by application to data synthesized from an intraoceanic subduction zone model. We then apply the method to transform an electrical conductivity cross-section across the Yangtze block and the North China Craton. The results show that the effective viscosity structure coincides well with that estimated from other independent datasets at depths of 40 to 80 km but differs slightly at depths of 100 to 200 km. We briefly discussed the potentials and associated problems for application.

Fault activation by hydraulic fracturing in western Canada.

Hydraulic fracturing has been inferred to trigger the majority of injection-induced earthquakes in western Canada, in contrast to the Midwestern United States, where massive saltwater disposal is the dominant triggering mechanism. A template-based earthquake catalog from a seismically active Canadian shale play, combined with comprehensive injection data during a 4-month interval, shows that earthquakes are tightly clustered in space and time near hydraulic fracturing sites. The largest event [moment magnitude (MW) 3.9] occurred several weeks after injection along a fault that appears to extend from the injection zone into crystalline basement. Patterns of seismicity indicate that stress changes during operations can activate fault slip to an offset distance of >1 km, whereas pressurization by hydraulic fracturing into a fault yields episodic seismicity that can persist for months.

[Preparation and evaluation of Sudan Red I molecularly imprinted polymer].

The molecularly imprinted polymer (MIP) was prepared by precipitation polymerization using Sudan Red I as the template. To investigate the influence of porogenic solvent and the amount of template on recognition property, selective chromatographic evaluation and frontal chromatography were performed. The results indicated that the obtained MIP had the best affinity and selectivity to the template when the molar ratio of template to functional monomer was 1:8 and a mixture of 30 mL methanol and 10 mL acetonitrile was used as the porogenic solvent. The imprinted factor of optimal MIP for Sudan Red I was 2.32, and the total amount of the immobilized ligand was 0.50 micromol/g. This MIP displayed good specific recognition property for Sudan Red I and was used as the sorbent of solid phase extraction (SPE) to determine trace Sudan Red I in chili powders. The linear range was from 10 to 500 micromol/L with a correlation coefficient of 0.999. The detection limit was 3.3 micromol/L, the spiked recovery was between 95.87% and 98.41%, and the relative standard deviation (RSD) was lower than 3.1%. The developed method can be used for the routine detection of Sudan Red I in chili powders.