Activation of the NF-κB pathway is strictly regulated to prevent excessive inflammatory and immune responses. In a well-known negative feedback model, IκBα-dependent NF-κB termination is a delayed ...response pattern in the later stage of activation, and the mechanisms mediating the rapid termination of active NF-κB remain unclear. Here, we showed IκBα-independent rapid termination of nuclear NF-κB mediated by CLK2, which negatively regulated active NF-κB by phosphorylating the RelA/p65 subunit of NF-κB at Ser180 in the nucleus to limit its transcriptional activation through degradation and nuclear export. Depletion of CLK2 increased the production of inflammatory cytokines, reduced viral replication and increased the survival of the mice. Mechanistically, CLK2 phosphorylated RelA/p65 at Ser180 in the nucleus, leading to ubiquitin‒proteasome-mediated degradation and cytoplasmic redistribution. Importantly, a CLK2 inhibitor promoted cytokine production, reduced viral replication, and accelerated murine psoriasis. This study revealed an IκBα-independent mechanism of early-stage termination of NF-κB in which phosphorylated Ser180 RelA/p65 turned off posttranslational modifications associated with transcriptional activation, ultimately resulting in the degradation and nuclear export of RelA/p65 to inhibit excessive inflammatory activation. Our findings showed that the phosphorylation of RelA/p65 at Ser180 in the nucleus inhibits early-stage NF-κB activation, thereby mediating the negative regulation of NF-κB.
Ti and Ti alloys are bioinert materials and two frequent problems associated with them are bacterial infection and lack of osteogenic potential for rapid bone integration. To overcome the problems, ...the present study incorporated strontium (Sr) and silver (Ag) simultaneously into porous TiO2 coatings through a single‐step technique, micro‐arc oxidation (MAO). Incorporation of Sr and Ag brought no significant changes to coating micromorphology and physicochemical properties, but endowed TiO2 coatings with both strong antibacterial activity and osteogenic ability. Antibacterial activity increased with Ag contents in the coatings. When Ag content reached 0.58 wt%, the coating showed both excellent short‐term (100.0%) and long‐term (77.6%) antibacterial activities. Sr/Ag‐containing coatings with 18.23 wt% Sr and 0.58 wt% Ag also presented good cytocompatibility for preosteoblast adhesion and proliferation, and promoted preosteoblast osteogenic differentiation both short‐termly and long‐termly. However, higher Ag content (1.29 wt%) showed toxic effects to preosteoblasts. In summary, MAO is a simple and effective way to incorporate Sr and Ag into porous TiO2 coatings and Sr/Ag‐containing TiO2 coating with 18.5 wt% Sr and 0.58 wt% Ag has both good osteogenic activity and strong antibacterial capability short‐termly and long‐termly. Therefore, such coatings are valuable for clinical application to strengthen osseointegration and long‐term high quality use of titanum implants.
The Late Cretaceous tectonic evolution of NE China reflects a complex history of extensional, contractional and strike-slip deformation as a result of the Mesozoic geodynamics of the active margin of ...East Asia. The NNE–trending, late Jurassic–Cretaceous sedimentary basins in the region display a complete structural record to analyze the nature of deformational events, and a unique stratigraphic archive to discern sediment sources and drainage patterns during their evolution. Here we evaluate the Upper Cretaceous lithostratigraphy and the internal structure of a series of sedimentary basins based on detailed seismic reflection profiles, surface geology and new zircon geochronology, interpret the mode of accommodation space and drainage pattern development in these basins, and present a new tectonic model for their post-rift evolution in the late Cretaceous. The basins occur in three NNE–oriented, subparallel zones, the Eastern (EZ), Central (CZ) and Western (WZ) Zones, in which the distribution, scale and intensity of deformational structures show major variations from the east to the west. The EZ basins include Sanjiang, Boli and Jixi, bounded on the west by the Zhangguangcai range (ZGCR). The CZ is represented by the ~400-km-wide Songliao Basin, which is bounded on the west by the Great Xing'an Range (GXAR). The WZ contains the Genhe, Erlian and Hailar Basins that are delimited by the Mongol–Okhotsk Suture to the north and the west. The Paleozoic Central Asian Orogenic Belt (CAOB), the northern North China Craton (NCC) and the Jiamusi Block (JMB) constitute the basement of these basins. The Early Cretaceous sedimentary record and structural fabric in all the basins resulted from ESE–WNW extension, manifested in NNE- oriented half and full grabens with listric fault geometries and growth fault structures. The Upper Cretaceous stratigraphy in some of these basins display internal unconformities indicating periods of non-deposition, and folds and thrust/reverse faults attesting to contractional deformation episodes in their sedimentary–tectonic records. The Upper Cretaceous basinal strata in the EZ show early Cenomanian–Turonian and early Campanian–Maastrichtian unconformities, consistent with the timing of two discrete episodes of regional contraction in the region. Basement-involved, predominantly E-vergent imbricate thrust faults, positive flower structures, and fault-propagation folds widely occur in the Upper Cretaceous strata of the EZ basins. The dominant drainage direction in these basins was to the W during the late Cenomanian–early Campanian. The nearly 5-km-thick Upper Cretaceous strata of the Songliao Basin in the CZ display a complete depositional record with no unconformity, but with two major episodes of drainage pattern switches. The first switch occurred near the Cenomanian–Turonian boundary with the fluvial systems draining N-NE, instead of W, and carrying sediments derived mainly from NCC. This change coincided with the eastward migration of the main depocenter in the basin. Following the development of a deep, large lake within the basin during the Turonian (92–86Ma) and then during the Santonian (~86–84.5Ma), the lacustrine environment experienced rapid shrinking and shallowing, and the drainage patterns changed from an axial (NNE–SSW) to a transverse (mainly to the W) system since 84Ma during Late Cretaceous. The main depocenter migrated to the W within the basin, and the main provenance became ZGCR and JMB to the E–SE. Contractional deformation affected the Songliao depocenter first at the Cenomanian–Turonian boundary and then in the early Campanian-Maastrichtian. The WZ basins experienced non-deposition during much of the late Cretaceous. The uppermost Cretaceous strata in the WZ are represented by fluvial and shallow lacustrine deposits, which show transpressional faults and folds.
We infer that the post-rift development of the sedimentary basins and hence the crustal evolution of NE China in the late Cretaceous were mainly controlled by the continental margin tectonics and plate interactions between the Okhotomorsk block (OB), part of the Izanagi oceanic realm, and East Asia. The initial arrival of OB at the East Asia Trench around 100–89Ma caused the first episode of contractional deformation across the sedimentary basins, and resulted in major shifts in their drainage patterns. The NE translation of OB along the sinistral transform plate boundary during 84–77Ma exerted a transpressional stress regime, which produced positive flower structures and thrust faults across the basins. The final collision of OB with Siberia–Sakhalin to the north ~70–65Ma resulted in further shortening and inversion within the CZ–WZ basins, and in reactivation of previously formed normal faults as thrust faults.
Transition metal dichalcogenide (TMD) nanosheets have evoked enormous research enthusiasm and have shown increased potentials in the biomedical field. However, a great challenge lies in ...high-throughput, large-scale, and eco-friendly preparation of TMD nanosheet dispersions with high quality. Herein, we report a universal polyphenol-assisted strategy to facilely exfoliate various TMDs into monolayer or few-layer nanosheets. By optimizing the exfoliation condition of molybdenum disulfide (MoS2), the yield and concentration of as-exfoliated nanosheets are up to 60.5% and 1.21 mg/mL, respectively. This is the most efficient aqueous exfoliation method at present and is versatile for the choices of polyphenols and TMD nanomaterials. The as-exfoliated MoS2 nanosheets possess superior biomedical stability as nanocarriers to load antibiotic drugs. They show a high photothermal conversion effect and thus induce a synergetic effect of chemotherapy and photothermal therapy to harvest enhanced antibiofilm activity under near-infrared (NIR) light. All these results offer an appealing strategy toward the synthesis and application of ultrathin TMD nanosheets, with great implications for their development.
Mussel-inspired polydopamine (PDA) coatings have been broadly exploited for constructing functional membrane surfaces. One-step codeposition of PDA with antifouling polymers, especially zwitterionic ...polymers, has been regarded as a promising strategy for fabricating antifouling membrane surfaces. However, one challenge is that the codeposition is usually a slow process over 10 h or even several days. Herein, we report that CuSO4/H2O2 is able to notably accelerate the codeposition process of PDA with poly(sulfobetaine methacrylate) (PSBMA). In our case, PSBMA is facilely anchored to the polypropylene microporous membrane (PPMM) surfaces within 1 h with the assistance of PDA because of its strong interfacial adhesion. The PDA/PSBMA-coated PPMMs show excellent surface hydrophilicity, high water permeation flux (7506 ± 528 L/m2·h at 0.1 MPa), and an outstanding antifouling property. Moreover, the antifouling property is maintained after the membranes are treated with acid and alkali solutions as well as organic solvents. To recap, it provides a facile, universal, and time-saving strategy for exploiting high-efficiency and durable antifouling membrane surfaces.
Aryldiazonium salts as coupling agents for surface chemistry have evidenced their wide applications for the development of sensors. Combined with advances in nanomaterials, current trends in sensor ...science and a variety of particular advantages of aryldiazonium salt chemistry in sensing have driven the aryldiazonium salt-based sensing strategies to grow at an astonishing pace. This review focuses on the advances in the use of aryldiazonium salts for modifying interfaces in sensors and biosensors during the past decade. It will first summarize the current methods for modification of interfaces with aryldiazonium salts, and then discuss the sensing applications of aryldiazonium salts modified on different transducers (bulky solid electrodes, nanomaterials modified bulky solid electrodes, and nanoparticles). Finally, the challenges and perspectives that aryldiazonium salt chemistry is facing in sensing applications are critically discussed.
Incremental learning is an alternative approach for maintaining knowledge by utilizing previous computational results of dynamic data contexts. As a new and important part of incremental learning, ...incremental Concept-cognitive learning (CCL) is an emerging field of concerning evolution of object or attributes sets and dynamic knowledge processing in the dynamic big data. However, existing incremental CCL algorithms still face some challenges that improve the generalization ability of new concepts, and the previously acquired knowledge should be efficiently utilized to reduce the computational complexity of the algorithm. At the same time, formal concept analysis has become a potential direction of cognitive computing, which can describe the processes of CCL. Attribute topology (AT) as a new representation of formal concepts can clearly display the relationship between new data and original data for reducing the complexity of the CCL process; therefore, we present an incremental concept-cognitive algorithm based on AT for incremental concept calculation, which is expressed by a concept tree. First, a relationship between the new object and some of the original objects is established. Then, on the basis of this finding, we propose an algorithm for updating the concept and presenting them through a concept tree. The algorithm determines the position and subtree of the new object by the relationship between the object and the original objects. Finally, an example is presented to demonstrate that the concept update algorithm based on AT is feasible and effective, and different orders of increments will result in different concept tree structures.
Plant spermatogenesis is a complex process that directly affects crop breeding. A rapid change in gene abundance occurs at early meiosis prophase, when gene regulation is selective. However, how ...these genes are regulated remains unknown. Here, we show that rice reproductive phasiRNAs are essential for the elimination of a specific set of RNAs during meiotic prophase I. These phasiRNAs cleave target mRNAs in a regulatory manner such that one phasiRNA can target more than one gene, and/or a single gene can be targeted by more than one phasiRNA to efficiently silence target genes. Our investigation of phasiRNA-knockdown and PHAS-edited transgenic plants demonstrates that phasiRNAs and their nucleotide variations are required for meiosis progression and fertility. This study highlights the importance of reproductive phasiRNAs for the reprogramming of gene expression during meiotic progression and establishes a basis for future studies on the roles of phasiRNAs with a goal of crop improvement.
There is a broad consensus that the extensive late Mesozoic igneous rocks in NE China were generated in an extensional setting. However, the timing and mechanism of the lithospheric extension remain ...controversial. To address this, we carried out an integrated study involving LA–ICP–MS zircon U–Pb dating and geochemical analyses (major elements, trace elements, and Hf isotopes) for the Early Cretaceous adakitic lavas and A-type rhyolites of the Songliao Basin. The adakitic lavas are andesites and dacites. The U–Pb dating of zircons from the adakitic lavas and A-type rhyolites yielded ages between 115 and 102 Ma. Geochemically, the adakitic lavas are characterized by high Sr contents (515–1610 ppm) and low Y (0.98–17.58 ppm) and heavy rare earth element (HREE) contents, and they therefore have high Sr/Y (51–112) ratios. They also exhibit high Mg# values (36–57) and high contents of MgO (0.56–3.53 wt%), Cr (15.7–87.3 ppm), and Ni (6.7–44.7 ppm) that are comparable with those of high-Mg adakitic rocks. The A-type rhyolites show an affinity with aluminous A-type magmatic rocks, and they are metaluminous to peraluminous (A/CNK = 0.98–1.35), enriched in alkalis, Ga, Zr, Nb, and Y, depleted in Sr and P, and exhibit fractionated REE patterns with negative Eu anomalies (Eu/Eu* = 0.05–0.77). All the primary zircons from the adakitic lavas and A-type rhyolites have positive εHf(t) values of +3.6 to +12.1 and juvenile two-stage model (TDM2) ages of 934–392 Ma. The adakitic lavas probably resulted from the partial melting of a delaminated region of the lower continental crust, with the magmas subsequently interacting with mantle materials upon ascent, while the A-type rhyolites were probably generated by the partial melting of a dehydrated charnockitic middle–lower crust. The data suggest that the adakitic lavas and the A-type rhyolites formed in an extensional environment related to the rollback of the subducting Paleo-Pacific Plate. The upwelling of asthenospheric mantle and local delamination of the lithosphere, which were induced by rollback of the subducting Paleo-Pacific Plate, extended from the Great Xing'an Range southeastward through the Songliao Basin to eastern Heilongjiang and Jilin provinces, giving rise to the southeastward migration of lithospheric extension and extension-related volcanism after ca. 140 Ma.
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•Early Cretaceous adakitic lavas and A-type rhyolites are identified in the Songliao Basin.•Adakitic lavas resulted from partial melting of the delaminated lower-crustal materials.•A-type rhyolites were generated by partial melting of a dehydrated middle–lower crust.•Lithospheric extension was induced by rollback of the Paleo-Pacific Plate.
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