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With the advancement of modern science and technology, large scientific facilities are increasingly oriented toward demand and application, and can be used for basic research as well as serving multiple disciplines. Developing large scientific facilities and related analytical technologies enhances understanding of large scientific facilities and popularizes their application in research across multiple disciplines. The combination of light or neutron sources from large scientific facilities and advanced analytical technologies can be achieved for materials structure information, dynamics study of chemical reactions, high dissociation of biomolecules, 3D visualization of energy materials or biological samples, etc. We first introduce the progress of domestic large scientific facilities of synchrotron radiation (SR) and free electron lasers (FELs) with different wavelengths and neutron sources. We further discuss the comparison between Chinese and typical foreign facilities in X-ray radiation from X-ray tubes, synchrotrons, X-ray FELs, and neutron sources based on physical parameters of light and neutron sources. In addition, we focus on the technological progress and perspectives combined with advanced X-ray radiation and neutron sources of large scientific facilities in China, especially in the nanoscience fields of energy catalysis and biological science. We hope that this roadmap will provide references on technology and methods to experimental users, as well as prospects for future development of technologies based on large research infrastructure facilities. Comprehensive studies and guidelines for basic research to practical application in various disciplines can be made with the assistance of large scientific facilities.

Artificial photosynthesis, which converts CO2into value-added chemicals and fuels, is of enormous potential in overcoming both global environmental problems and energy crisis. However, the development of CO2photoconversion catalysts with high efficiency remains a great challenge due to the thermodynamic stability and dynamics sluggishness of CO2. Herein, a superior hierarchical porous cobalt single-atom photocatalyst featuring highly dispersed Co isolated single atomic sites on micro-mesoporous nitrogen-doped carbon (0.8-Co-ISAS/MMNC-900) is developed and characterized, which significantly boosts the photoreduction of CO2-to-CO. The 0.8-Co-ISAS/MMNC-900 catalyst achieves a high 7261 µmol g−1h−1CO formation rate, an impressive 90.1% CO selectivity, as well as an decent stability during four times cycling test, indicating a boosted CO2photoconversion property. Experimental data and theoretical results reveal that the hierarchically porous structure can promote the formation of exterior local electric field caused by charge separation as well as the synergic role of Co ISASs and micro-mesoporous configuration can facilitate photo-excited electron accumulation, CO2adsorption and activation, and *COOH intermediate formation. This work develops a novel strategy to synthesize superior photocatalysts for CO2reduction through multiscale porous structural engineering.

Recent advancements in data-driven deep-learning methods have significantly improved rolling bearing fault diagnosis. However, these frameworks face limitations due to data defects and inadequate feature extraction. To overcome these obstacles, this article proposes a novel feature extraction and causal model-based diagnosis framework. This framework leverages causal discovery to derive causal models from real data, accurately estimate causal effects, and enhance fault diagnosis performance. Specifically, the proposed framework utilizes the time-reassigned synchrosqueezing transform (TSST) to process collected rolling bearing signals, transforming them from the time domain to the time–frequency (TF) domain. This transformation enables the extraction of energy distribution and frequency components of vibration signals at different frequencies, effectively reducing noise interference. Subsequently, a directed acyclic graph (DAG) is constructed using an ordering-based causal discovery method to identify potential interfering factors that may impact vibration signals, facilitating causal effects estimation. Furthermore, by integrating the vision transformer (ViT) network with causal effects estimation techniques, the framework achieves end-to-end rolling bearing fault diagnosis. Experimental results on laboratory-bearing datasets demonstrate the superior performance of this proposed fault diagnosis framework compared to existing methods.

Fault diagnosis of bearings plays a critical role in the predictive maintenance and health management of mechanical equipment. However, compound faults diagnosis of bearings remains a challenging task, because compound faults are coupled together by multiple single faults, which are difficult to decouple and identify. In addition, in industrial scenarios, collecting sufficient compound fault samples for model training is unrealistic. To address these issues, we propose a generative zero-shot compound fault diagnosis model based on semantic alignment. The model includes a semantic alignment module, feature extraction module, generative adversarial module, and classification module. First, we propose a feature extractor that combines channel and spatial attention mechanisms to extract fault features from the original vibration signals. Second, we designed a novel fault semantic construction method that combines interpretable priori fault semantics in time–frequency domain and hidden feature distribution alignment. Third, in the generative adversarial module, we combine supervised contrastive loss and comparator into the improved Wasserstein generative adversarial networks with gradient penalty (WGANs_GP) to learn the mapping relationship between fault semantics and fault features. Finally, we use the pseudocompound faults features generated by the generator to train a classifier for classifying ground-truth unseen compound fault. The effectiveness of the proposed method is verified on a self-built bearing test bench, and the results show that the proposed model can achieve classification accuracy of 89.25% for compound faults under the condition of only using single-fault samples for training.

In recent years, with the continuous development of photoactive layer material, the power conversion efficiency (PCE) of bulk heterojunction (BHJ) binary organic solar cells (BOSCs) has been significantly improved. However, it is difficult for BOSCs to maximize the effective utilization of the wide spectrum of solar energy, limiting the further improvement of PCE. Adding a third component to BOSCs that constructing ternary organic solar cells (TOSCs) is an effective method to broaden the absorption spectrum of BOSC, match the gradient energy level, and regulate the morphology of the active layer. Constructing TOSCs can not only effectively improve the device performance, but also maintain the advantages of easy‐to‐fabricate single‐junction device structures. In this review, we first introduced the basic working mechanism of TOSCs. Then based on the working mechanism, we comprehensively reviewed the latest research results of TOSCs, and analyzed the effects of the third component on the microscopic morphology of the active layer, photovoltaic performance and device stability. Finally, we systematically summarized the role of the third component in TOSCs and proposed some future development trends of TOSCs, such as designing and synthesizing more economical, green, and environmentally friendly TOSCs that towards the commercial application in the future.

Mechanical properties play a crucial role in the degradation of battery performance, and a comprehensive understanding of particle crack formation is vital for optimizing battery materials. Here, we focus on Mo2C, a promising anode material for lithium-ion batteries, and we employ soft X-ray tomography to observe the internal structure of Mo2C particles at different cycle numbers. The growth and evolution of cracking have been quantified by analyzing the porosity and morphological complexity of the particles based on the reconstruction images. Furthermore, considering the tendency for hole formation during particle preparation, we investigate the impact of such defects on crack propagation and the evolution of cracking. Irreversible cracking during cell operation can significantly contribute to the degradation of the Mo2C anode performance. In addition, the presence of internal defects in the particles influences the direction of crack propagation and intensifies the evolution of cracking. This study offers valuable insights into the synthesis and modification strategies for Mo2C materials, which can help enhance battery performance.

Rational control and understanding of isomerism are of significance but still remain a great challenge in reticular frameworks, in particular, for covalent organic frameworks (COFs) due to the complicated synthesis and energy factors. Herein, reaction of 3,3′,5,5′-tetra(4-formylphenyl)-2,2′,6,6′-tetramethoxy-1,1′-biphenyl (TFTB) with 3,3′,5,5′-tetrakis(4-aminophenyl)bimesityl (TAPB) under different reaction conditions affords single crystals of two 3D COF isomers, namely, USTB-20-dia and USTB-20-qtz. Their structures with resolutions up to 0.9–1.1 Å have been directly solved by three-dimensional electron diffraction (3D ED) and synchrotron single crystal X-ray diffraction, respectively. USTB-20-dia and USTB-20-qtz show rare 2 × 2-fold interpenetrated dia-bnets and 3-fold interpenetrated qtz-bframeworks. Comparative studies of the crystal structures of these COFs and theoretical simulation results indicate the crucial role of the flexible molecular configurations of building blocks in the present interpenetrated topology isomerism. This work not only presents the rare COF isomers but also gains an understanding of the formation of framework isomerism from both single crystal structures and theoretical simulation perspectives.

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Non-alcoholic fatty liver disease (NAFLD) has become a growing public health problem. However, the complicated pathogenesis of NAFLD contributes to the deficiency of effective clinical treatment. Here, we demonstrated that liver-specific loss of Arid2induced hepatic steatosis and this progression could be exacerbated by HFD. Mechanistic study revealed that ARID2 repressed JAK2-STAT5-PPARγ signaling pathway by promoting the ubiquitination of JAK2, which was mediated by NEDD4L, a novel E3 ligase for JAK2. ChIP assay revealed that ARID2 recruited CARM1 to increase H3R17me2a level at the NEDD4L promoter and activated the transcription of NEDD4L. Moreover, inhibition of Jak2 by Fedratinib in liver-specific Arid2knockout mice alleviated HFD-induced hepatic steatosis. Downregulation of ARID2 and the reverse correlation between ARID2 and JAK2 were also observed in clinical samples. Therefore, our study has revealed an important role of ARID2 in the development of NAFLD and provided a potential therapeutic strategy for NAFLD.

Topochemical polymerization of molecular crystals into porous materials is of significance due to their promising applications in the field of adsorption and catalysis, yet rarely reported due to the synthesis difficulty. Herein, a hydrogen-bonded organic framework (HOF-45) has been fabricated by the crystallization of a cage-like building block containing three alkynyl groups. It exhibits almost mesoporous structure demonstrated by single crystal X-ray diffraction study. Light-driven topochemical polymerization of HOF-45 with ethanedithiol covalently links alkynyl groups in HOF-45, generating a hydrogen-bond and covalent-bond cross-linked material (HOF-45C). In contrast to HOF-45, cross-linked HOF-45C retains the crystalline nature and displays improved solution resistence according to the powder X-ray diffraction data. In particular, HOF-45C is able to support the growth of ultrafine palladium nanoparticles with the average size of ca. 1.9 nm for rapidly promoting the degradation of nitrophenol, methyl orange, and congo red with the help of NaBH4as well as Suzuki-Miyaura coupling reaction. This work inputs a new idea on the HOFs application in preparing covalent-linked porous organic materials.

This paper studies the coordinated planning of transmission tasks in the heterogeneous space networks to enable efficient sharing of ground stations cross satellite systems. Specifically, we first formulate the coordinated planning problem into a mixed integer liner programming (MILP) problem based on time expanded graph. Then, the problem is transferred and reformulated into a consensus optimization framework which can be solved by satellite systems parallelly. With alternating direction method of multipliers (ADMM), a semi-distributed coordinated transmission task planning algorithm is proposed, in which each satellite system plans its own tasks based on local information and limited communication with the coordination center. Simulation results demonstrate that compared with the centralized and fully-distributed methods, the proposed semi-distributed coordinated method can strike a better balance among task complete rate, complexity, and the amount of information required to be exchanged.

Efficient data sharing in autonomous driving is expected to improve road safety. However, time-varying network topologies, limited roadside unit (RSU) coverage, and communication limitations make efficient data sharing challenging. Therefore, we propose an RSU-assisted hybrid scheduling (RAHC) scheme, including centralised scheduling within the RSU and self-organised scheduling in the RSU blind zone. For centralised scheduling, we model data transmission and transmission conflicts as conflict graph based on real-time network topology, and solve for optimal transmission paths while satisfying communication constraints, and increase the chance for vehicles in RSU blind areas to obtain data by carrying and forwarding data. For self-organised scheduling, we use degree of link similarity (DLS) to cluster vehicles and select the vehicle with the largest service capacity (SC) in the cluster to serve the opposite vehicle. This reduces duplication and redundancy of data transmission and improves sharing efficiency. Simulation results demonstrate the superiority of the solution.

Tau protein is implicated in the pathogenesis of Alzheimer’s disease (AD) and other tauopathies, but its physiological function is in debate. Mostly explored in the brain, tau is also expressed in the pancreas. We further explored the mechanism of tau’s involvement in the regulation of glucose-stimulated insulin secretion (GSIS) in islet β-cells, and established a potential relationship between type 2 diabetes mellitus (T2DM) and AD. We demonstrate that pancreatic tau is crucial for insulin secretion regulation and glucose homeostasis. Tau levels were found to be elevated in β-islet cells of patients with T2DM, and loss of tau enhanced insulin secretion in cell lines, drosophila, and mice. Pharmacological or genetic suppression of tau in the db/dbdiabetic mouse model normalized glucose levels by promoting insulin secretion and was recapitulated by pharmacological inhibition of microtubule assembly. Clinical studies further showed that serum tau protein was positively correlated with blood glucose levels in healthy controls, which was lost in AD. These findings present tau as a common therapeutic target between AD and T2DM.

Two-dimensional (2D) porphyrin-based covalent organic frameworks (COFs) are one of the most promising candidates for photocatalytic carbon dioxide reduction reaction (CO2RR), which however still suffer from the hindered mass transfer during the catalysis procedure associated with the close packing of 2D COF layers due to the strong axial π–π stacking. Herein, condensation between the porphyrinic aldehydes p-MPor-CHO (M = H2, Co, and Ni) and 3,8-diamino-6-phenyl-phenanthridine (DPP) affords new porphyrin-based 2D COF architecture MPor-DPP-COFs (M = H2, Co, and Ni). The bulky phenyl substituent at the phenanthridine periphery of the linking unit reduces the axial π–π stacking, providing an enlarged inter-layer spacing of 6.0 Å according to high-resolution transmission electron microscopy. This, in combination with the large surface area (1021 m2g–1) revealed by nitrogen sorption measurements at 77 K for CoPor-DPP-COF possessing electroactive Co ions, endows it with excellent photocatalytic activity for CO2RR with a CO generation rate of 10 200 μmol g–1h–1and a CO selectivity up to 82%. This work affords new ideas for achieving efficient photocatalytic CO2RR upon fine-tuning the inter-layer spacing of 2D COFs.

In this paper, we have effectively demonstrated 150 nm-gate-length AlGaN/GaN high electron mobility transistors (HEMTs) on 4-inch SiC substrate. The 150 nm gate-length was accomplished by utilizing traditional I-line stepper photolithography, together with a nitride spacer side-wall. This method offers superior processing efficiency compared to E-beam lithography with high wafer uniformity. The devices processed with this spacer side-wall aided method demonstrated comparable electrical performances as that of E-beam processed one with fTof 45 GHz, fMAXof 80 GHz, Pout of 31 dBm and PAE of 45% at 29 GHz, which can be imported to large scale manufacturing.

Dynamic covalent imine reactions between 2′,3′-dimethoxy-[1,1′:4′,1″-terphenyl]-3,3″,5,5″-tetracarbaldehyde (DMTT) and cyclohexanediamine, p-phenylenediamine, and benzidine, respectively, generate a porous organic cage (DMPOC) and two covalent organic frameworks (COFs), USTB-29, and USTB-30. DMPOC shows a [3 + 6] topological cage-like structure according to single crystal X-ray diffraction result. In contrast, both microcrystalline USTB-29 and USTB-30 exhibit two-dimensional monoporous structures in an eclipsed AA stacking style based on powder X-ray diffraction and theoretical simulations. In addition, DMPOC is capable of efficiently absorbing the iodine vapor with an outstanding uptake of 5.10 g/g, much higher than that of USTB-29 (3.07 g/g) and USTB-30 (3.16 g/g). Cage to COFs transformations have been realized from DMPOC to USTB-29 and USTB-30 viathe imine bond exchange with slightly increased iodine vapor uptake. Mechanism investigations uncover that both nitrogen and oxygen atoms of POC and COFs contribute to iodine vapor capture due to the formation of charge transfer matter, and loose interaction introducing adaptive expanding voids of DMPOC is suggested to capture more iodine vapor than that of COFs with strong π-πinteractions.

The resurgence of visible light photocatalysis for carbon dioxide reduction reaction (CO2RR) has resulted in the generation of various homogeneous and heterogeneous paradigms. Herein, a new system has been established by incorporating dual catalytic sites into porous coordination polymer toward the photocatalysis of CO2RR. A functional ligand, 5,10,15,20-tetrakis[4′-(terpyridinyl)phenyl]porphyrin (TTPP), has been used to assemble discrete divalent nickel ions into the coordination polymer (TTPP-Ni) through metal bis(terpyridine) nodes. Both the porphyrin and terpyridine moieties prefer to bind with nickel ions, giving rise to TTPP-Ni with dual active catalytic sites. By controlling different molar ratios of ligand and metal and the reaction temperature, four samples including TTPP-Ni-n(n= 1, 2, 3, and 4) with different molar ratios of nickel porphyrin and nickel bis(terpyridine) subunits have been fabricated. The predesigned two-dimensional chemical structures of TTPP-Ni samples have been fully characterized using powder X-ray diffraction, X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and IR and UV–vis spectroscopies. The photocatalytic activities of these coordination polymers have been screened using [Ru(bpy)3]Cl2·6H2O as a photosensitizer together with triisopropanolamine as the sacrificial electron donor in CH3CN and H2O. Among these photocatalysts, TTPP-Ni-3 and TTPP-Ni-4 with almost saturated metal sites are able to display extraordinary photocatalytic performance including a CO generation rate of ca. 3900 μmol g–1h–1and 98% selectivity. The mechanism associated with dual active sites has been rationalized on the basis of theoretical simulations.

Lung cancer is the most common malignancy and the leading cause of cancer death worldwide, and lung adenocarcinoma (LUAD) is the most prevalent subtype. Considering the emergence of resistance to therapies, it is urgent to develop more effective therapies to improve the prognosis. Here we reported that pancreatic progenitor cell differentiation and proliferation factor (PPDPF) deficiency inhibited LUAD development both in vitro and in vivo. Mechanistically, PPDPF induces hyperactive STAT3 by interfering STAT3-PTPN1 interaction. Activated STAT3 promoted BMPR2 transcription, which further inhibited apoptosis. Moreover, PPDPF reduced NK cell infiltration and activation to develop an immunosuppressive microenvironment, which was also mediated by STAT3. Furthermore, we identified that the expression of PPDPF was positively correlated with the malignant features of LUAD, as well as BMPR2 and p-STAT3 level in clinical samples. Therefore, our study suggests that PPDPF positively regulates BMPR2 expression and facilitates immune escape via regulating STAT3 activity, providing a potential therapy target for LUAD.

Semaphorin 3A (Sema3A) has been recognized as a crucial regulator of morphogenesis and homeostasis over a wide range of organ systems. However, its function in cutaneous wound healing is poorly understood. In our study, we demonstrated that Sema3A adenovirus plasmids transfection limited keratinocyte proliferation and decreased migrative capacity as assessed by in vitro wound healing assay. Sema3A transduction inhibited TGF-β1-mediated keratinocyte migration and EMT process. Besides, we applied mice with K14-Cre-mediated deletion of Sema3A and found that Sema3A depletion postponed wound closure with decreased re-epithelialization and matrix growth. Contrary to the results obtained with full-length Sema3A plasmids transfection, increased keratinocyte migration with recombinant Sema3A proteins resulted in quicker closure of the wounding area after a scratch. Further, exogenously applied recombinant Sema3A worked with EGF to maintain the activation of EGFR by interacting with NRP1 and thereby regulated the internalization of the EGFR-NRP1 complex. Taken together, these results indicated a paradoxical role of autonomous and non-autonomous Sema3A expression during wound healing. Combined administration of recombinant EGF and Sema3A proteins could accelerate the process of wound repair, thus providing promising treatment prospects in the future.

An open cluster is an ideal region to study the evolution of stars. In this work, we use Gaia Early Data Release 3 (Gaia EDR3) to derive the fundamental parameters of 30 faint open clusters listed in the catalogue given by Cantat-Gaudin et al. (2018, A&A, 618, A93), but the Gmagnitude of all of the member stars of that catalogue is brighter than ∼18 mag. This catalogue does not provide isochrone fitting parameters and spatial structure parameters. We acquired the member stars of 30 open clusters using the Density-Based Spatial Clustering of Applications with Noise algorithm in Gaia EDR3. The Gmagnitude of the member stars using our method can be found down to ∼21 mag. The G-band, GBP-band, and GRP-band data of the member stars construct a good color–magnitude diagram, which can further ensure the precision of isochrone fitting. We also calculated the spatial structure parameters, which are the core radius and the limiting radius, using Markov chain Monte Carlo algorithm.

Contact binary stars are important research objects in astrophysics. The calculation speed of deriving the parameters of contact binaries with the Wilson–Devinney program and the Phoebe with Markov chain Monte Carlo (MCMC) program is relatively slow. It is unrealistic to derive the parameters in batches with the program for sky survey data. We obtain a neural network model of supervised learning with the training of synthetic light curves with Phoebe. We calculate the parameters of eight special targets from the simulated data and the Kepler data. Then, we generate the new light curve to fit the light curve of the special target base on these parameters. The correlation index R2of the fitting result is more than 0.98. The method can be used to fit the target which has orbital inclinations greater than 50°. By fitting the Kepler data and the observed data on the ground, the method has a good generalization ability to these targets, which have some noise and some starspots. The calculation speed of one light curve with this method is less than seconds. We can derive the parameters quickly in batches to undertake some statistical work for sky survey data with the method.

Objective: To observe effects of medication use on small airway function, airway inflammation and acute exacerbations in patients with clinically controlled asthma. Methods: Forced expiratory flow over the middle half of the forced expiratory curve (FEF25%–75%), percentage of eosinophil, concentrations of eosinophil cationic protein (ECP) and interleukin (IL)-5 in induced sputum were assessed in patients with clinically controlled asthma who were given oral anti-inflammatory agents alone or in combination with inhaled therapy and inhaled therapy alone. Subsequently, acute exacerbations were compared between two groups during the 24-week follow-up period. Results: FEF25%–75%in 43 patients with clinically controlled asthma given oral anti-inflammatory agents alone or in combination with inhaled therapy was significantly higher than that in 49 patients given inhaled therapy alone. Meanwhile, the percentage of eosinophils and levels of IL-5 and ECP in patients with clinically controlled asthma given oral anti-inflammatory agents alone or in combination with inhaled therapy were significantly lower than those in patients given inhaled therapy alone. Additionally, the patients with clinically controlled asthma given inhaled therapy were likely to have more acute exacerbation than the patients given oral anti-inflammatory agents alone or in combination with inhaled therapy during the 24-week follow-up period. Conclusion: Systemic anti-inflammatory agents may have a greater effect on parameters reflecting small airway patency and reducing acute exacerbations, presumably secondary to reduction in airway inflammation.

The rapid development in synthesis methodology and applications for covalent organic frameworks (COFs) has been witnessed in recent years. However, the synthesis of highly stable functional COFs still remains a great challenge. Herein two-dimensional polyimide-linked phthalocyanine COFs (denoted as CoPc-PI-COF-1 and CoPc-PI-COF-2) have been devised and prepared through the solvothermal reaction of the tetraanhydrides of 2,3,9,10,16,17,23,24-octacarboxyphthalocyaninato cobalt(II) with 1,4-phenylenediamine and 4,4′-biphenyldiamine, respectively. The resultant CoPc-PI-COFs with a four-connected sql net exhibit AA stacking configurations according to powder X-ray diffraction studies, showing permanent porosity, thermal stability above 300 °C, and excellent resistance to a 12 M HCl aqueous solution for 20 days. Current–voltage curves reveal the conductivity of CoPc-PI-COF-1 and CoPc-PI-COF-2 with the value of 3.7 × 10–3and 1.6 × 10–3S m–1, respectively. Due to the same Co(II) electroactive sites together with similar permanent porosity and CO2adsorption capacity for CoPc-PI-COFs, the cathodes made up of COFs and carbon black display a similar CO2-to-CO Faradaic efficiency of 87–97% at applied potentials between −0.60 and −0.90 V (vs RHE) in 0.5 M KHCO3solution. However, in comparison with the CoPc-PI-COF-2&carbon black electrode, the CoPc-PI-COF-1 counterpart provides a larger current density (jCO) of −21.2 mA cm–2at −0.90 V associated with its higher conductivity. This cathode also has a high turnover number and turnover frequency, amounting to 277 000 and 2.2 s–1at −0.70 V during 40 h of measurement. The present result clearly discloses the great potential of 2D porous crystalline solids in electrocatalysis.

Cartilage degeneration has been reported to deteriorate osteoarthritis (OA), a prevalent joint disease caused by intrinsic and epigenetic factors. This study aimed to examine the molecular mechanism of enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2)/microRNA-138 (miR-138)/syndecan 1 (SDC1) and its epigenetic regulation in cartilage degeneration in OA. An OA cell model was induced by stimulating chondrocytes with interleukin (IL)-1β at a final concentration of 10 ng/mL, followed by alterations in EZH2 and miR-138 expression. Afterwards, cell apoptosis was analyzed using flow cytometry. The expression patterns of cartilage catabolism-related factors (MMP-13, ADAMTS-4, and ADAMTS-5) were determined using RT-qPCR and western blot analyses. The EZH2 and H3K27me3 enrichment at the miR-138 promoter region were determined using ChIP-qPCR. Finally, an OA mouse model was constructed to verify the function of EZH2 in vivo. EZH2 was expressed at high levels in OA models. EZH2 depletion ameliorated OA, as evidenced by reduced cell apoptosis in IL-1β-treated chondrocytes and decreased levels of cartilage catabolism-related factors. Moreover, EZH2 promoted histone methylation at the miR-138 promoter to suppress miR-138 expression, thereby upregulating the expression of SDC1, a target gene of miR-138. Changes in this pathway increased the expression of cartilage catabolism-related factors in vitro while promoting cartilage degeneration in vivo. Our data provided evidence that EZH2 inhibits miR-138 expression by promoting the histone methylation of its promoter, which induces cartilage degeneration in OA models by upregulating SDC1 expression, suggesting a novel mechanistic strategy for OA treatment.

Covalent organic frameworks (COFs) are notable for their remarkable structure, function designability, and tailorability, as well as stability, and the introduction of “open metal sites” ensures the efficient binding of small molecules and activation of substrates for heterogeneous catalysis and energy storage. Herein, we use the postsynthetic metal sites to catalyze polysulfide conversion and to boost the binding affinity to active matter for lithium–sulfur batteries (LSBs). A dual-pore COF, USTB-27, with hxltopology has been successfully assembled from the imine chemical reaction between 2,3,8,9,14,15-hexa(4-formylphenyl)diquinoxalino [2,3-a:2′,3′-c]phenazine and [2,2′-bipyridine]-5,5′-diamine. The chelating nitrogen sites of both modules are able to postsynthetically functionalize with single cobalt sites to generate USTB-27-Co. The discharge capacity of the sulfur-loaded S@USTB-27-Co composite in a LSB is 1063, 945, 836, 765, 696, and 644 mA h g–1at current densities of 0.1, 0.2, 0.5, 1.0, 2.0, and 5.0 C, respectively, much superior to that of non-cobalt-functionalized species S@USTB-27. Following the increased current densities, the rate performance of S@USTB-27-Co is much better than that of S@USTB-27. In particular, the capacity retention at 5.0 C has a magnificent increase from 19% for the latter species to 61% for the former one. Moreover, S@USTB-27-Co exhibits a higher specific capacity of 543 mA h g–1than that of S@USTB-27 (402 mA h g–1) at a current density of 1.0 C after electrochemical cycling for 500 runs. This work illustrates the “open metal sites” strategy to engineer the active chemical component conversion in COF channels as well as their binding strength for specific applications.

Chimeric antigen receptor (CAR)-engineered T cells (CAR-Ts) therapy has an excellent efficacy in cancer treatment, especially its impressive results in hematological malignancies. Unfortunately, its application on solid tumors is challenged by the off-target effects caused by lacking of tumor specific antigens and the immunosuppression caused by the tumor microenvironment. We constructed a switchable dual receptor CAR-T cell (sdCAR-T) whose activity relied upon double antigens (mesothelin and fluorescein isothiocyanate) and was strictly controlled by a “switch” (FPBM) consisting of a PD-L1 blocking peptide conjugated to fluorescein isothiocyanate. SdCAR-T cells were activated only when FPBM and cognate tumor cells expressing both PD-L1 and mesothelin coexist. Importantly, long-term proliferation experiments in vitroand the pharmacodynamic study in vivoshowed a stronger antitumor activity of this system compared to the second generation mesothelin CAR-T cells. In view of this novel treatment paradigm being safer and more effective than traditional CAR-T cells, it may become a new strategy for the treatment of solid tumors.

ABSTRACTIncreasing the level of AsA and maintaining proper lignin content will improve the quality of celery (Apium graveolens L.). However, the study on the regulation mechanism of genes related to AsA and lignin metabolism in celery was limited, especially in yellow celery. In this study, the accumulation of AsA and lignin and the expression profiles of related-genes were detected in three kinds of yellow celery. The results showed that the content of AsA was higher in the leaf blades of ‘Huangtaiji’ and the petioles of ‘Jinhuangqincai’. The content of lignin was the highest in ‘Jinhuangqincai’ leaves, followed by ‘Liuhehuangxinqin’ and ‘Huangtaiji’. The expression levels of AgAO(r= −0.032) and AgDHAR1(r= −0.193) genes involved in AsA recycling and degradation showed negatively correlated with AsA content. AgCCoAOMT(r= 0.692) and AgF5 H(r= 0.733) genes expression were positively correlated with lignin content, while the expression of AgCAD(r= −0.694) and AgC3ʹH(r= −0.722) genes were negatively correlated with lignin content. Our current work provided potential theoretical basis for effectively changing accumulation of AsA and lignin by genetic engineering in celery.