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The electrochemical CO2reduction reaction (CO2RR) is a promising approach to upgrading CO2into methane (CH4) and other high-value-added chemicals, critical for lowering carbon emissions and mitigating the greenhouse effect. However, the selectivity of CO2RR to methane remains low at the current densities required for commercialization. Herein, we report a simple one-step synthesis of monodisperse copper-based catalysts for efficient electromethanation of CO2. Through rational regulation of active sites, the selectivity for methane production can reach as high as 57.02% under the current density of 300 mA cm–2as a result of suppressed C–C coupling for improved *CO hydrogenation. This work offers an effective strategy to regulate Cu-based catalysts to manage the hydrogenation of *CO for CO2RR toward CH4formation.

Osteopetrosis is an inherited metabolic disease, characterized by increased bone density and narrow marrow cavity. Patients with severe osteopetrosis exhibit abnormal bone brittleness, anemia, and infection complications, which commonly cause death within the first decade of life. Pathologically, osteopetrosis impairs not only the skeletal system, but also the hemopoietic and immune systems during development, while the underlying osteoimmunological mechanisms remain unclear. Osteoclastic mutations are regarded as the major causes of osteopetrosis, while osteoclast non-autonomous theories have been proposed in recent years with unclear underlying mechanisms. Retinoic acid (RA), the metabolite of Vitamin A, is an essential requirement for skeletal and hematopoietic development, through the activation of retinoic acid signaling. RA can relieve osteopetrosis symptoms in some animal models, while its effect on bone health is still controversial and the underlying mechanisms remain unclear. In this study, we constructed an osteoblast-specific inhibitory retinoic acid signaling mouse model and surprisingly found it mimicked the symptoms of osteopetrosis found in clinical cases: dwarfism, increased imperfectly-formed trabecular bone deposition with a reduced marrow cavity, thin cortical bone with a brittle skeleton, and hematopoietic and immune dysfunction. Micro-CT, the three-point bending test, and histological analysis drew a landscape of poor bone quality. Single-cell RNA sequencing (scRNA-seq) of the femur and RNA-seq of osteoblasts uncovered an atlas of pathological skeletal metabolism dysfunction in the mutant mice showing that osteogenesis was impaired in a cell-autonomous manner and osteoclastogenesis was impaired via osteoblast-osteoclast crosstalk. Moreover, scRNA-seq of bone marrow and flow cytometry of peripheral blood, spleen, and bone marrow uncovered pathology in the hematopoietic and immune systems in the mutant mice, mimicking human osteopetrosis. Results showed that hematopoietic progenitors and B lymphocyte differentiation were affected and the osteoblast-dominated cell crosstalk was impaired, which may result from transcriptional impairment of the ligands Pdgfdand Sema4d. In summary, we uncovered previously unreported pathogenesis of osteopetrosis-like disorder in mice with skeletal, hematopoietic, and immune system dysfunction, which was induced by the inhibition of retinoic acid signaling in osteoblasts, and sheds new insights into a potential treatment for osteopetrosis.

ABSTRACTCervical cancer is the most common malignant tumor in gynecology with high mortality rate, so novel approaches for cervical cancer treatment are urgently needed. In this study, we analyzed the gene expression data and clinicopathological data of The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression Project (GTEx) downloaded from University of California Santa Cruz (UCSC) Xena database. Chemokine (C-X-C motif) ligand 1 (CXCL1) was screened out as a key prognostic gene for cervical cancer. Revealed by the results of ELISA and Western blot, the expression of CXCL1 and chemokine (C-X-C motif) receptor 2 (CXCR2) in cervical cancer cell lines (HeLa and C33A) was significantly higher than that in the primary cervical epithelial cells. Cellular immunofluorescence was used in this study to observe CXCR2 localization. Through CCK8, clone formation assay, wound healing assay and Annexin V/PI staining, it was found that down-regulation of CXCL1 expression or treatment with CXCR2 antagonist (SB 225002) could reduce the cell viability, affect the proliferation, weaken the migration ability, and promote the apoptosis of cervical cancer cells; however, the effect of CXCR2 antagonist was improved after over-expressed CXCL1. CXCL1/CXCR2 chemokine system regulates the proliferation, migration, and apoptosis of cervical cancer cells in the form of an autocrine loop, thus affecting the development of cervical cancer. This study provides a theoretical basis for researching the molecular mechanism of cervical cancer deterioration and development, and brings forward a new idea for the prevention and treatment of cervical cancer.

Group 2 innate lymphoid cells (ILC2s) play crucial roles in mediating allergic inflammation. Recent studies also indicate their involvement in regulating tumor immunity. The tumor suppressor liver kinase B1 (LKB1) inactivating mutations are associated with a variety of human cancers; however, the role of LKB1 in ILC2 function and ILC2-mediated tumor immunity remains unknown. Here, we show that ablation of LKB1 in ILC2s results in an exhausted-like phenotype, which promotes the development of lung melanoma metastasis. Mechanistically, LKB1 deficiency leads to a marked increase in the expression of programmed cell death protein-1 (PD-1) in ILC2s through the activation of the nuclear factor of activated T cell pathway. Blockade of PD-1 can restore the effector functions of LKB1-deficient ILC2s, leading to enhanced antitumor immune responses in vivo. Together, our results reveal that LKB1 acts to restrain the exhausted state of ILC2 to maintain immune homeostasis and antitumor immunity.

The Ni-rich layered cathode material LiNi0.8Co0.1Mn0.1O2(NCM811) with high specific capacity and acceptable rate performance is one of the key cathode materials for high-energy-density lithium-ion batteries. Coprecipitation, the widely utilized method in the precursor synthesis of NCM811 materials, however, suffers long synthetic processes and challenges in uniform element distribution. The spray pyrolysis method is able to prepare oxide precursors in seconds where all transition-metal elements are well distributed, but the difficulty of lithium distribution will also arise when the lithium salts are added in the subsequent sintering process. Herein, a fresh one-step spray pyrolysis approach is proposed for preparing high-performance NCM811 cathode materials by synthesizing lithium-contained precursors in which all elements are well distributed at a molecular level. The precursors with folded morphology and exceptional uniformity are successfully obtained at a low pyrolysis temperature of 300 °C by an acetate system. Furthermore, the final products commendably inherit the folded morphology of the precursors and exhibit excellent cyclic retentions of 94.6% and 88.8% after 100 and 200 cycles at 1 C (1 C = 200 mA g–1), respectively.

To position personnel in mines, the study discussed in this paper built on the tunnel personnel positioning method on the basis of both TOA and location-finger print (LFP) positioning. Given non-line of sight (NLOS) time delay in signal transmission caused by facilities and equipment shielding in tunnels and TOA measurement errors in both LFP database data and real-time data, this paper puts forth a database data de-noising algorithm based on distance threshold limitation and modified mean filtering (MMF), as well as a real-time data suppression algorithm based on speed threshold limitation and MMF. On this basis, a nearest neighboring data matching algorithm based on historical location and the speed threshold limitation is used to estimate personnel location and realize accurate personnel positioning. The results from both simulation and the experiment suggest that: compared with the basic LFP positioning method and the method that only suppresses real-time data error, the tunnel personnel positioning methods based on TOA and modified LFP positioning permits effectively eliminating error in TOA measurement, making the measured data close to the true positional data, and dropping the positioning error: the maximal positioning error in measurements from experiment drops by 9 and 3m, respectively, and the positioning accuracy of 3m is achievable in the condition used in the experiment.

ObjectiveThe combination of coils and Onyx for the treatment of carotid-cavernous fistulas (CCFs) is an interesting new development. The purpose of the current study is to evaluate our preliminary experience with the combined use of coils and Onyx for the treatment of traumatic CCFs.MethodsBetween April 2009 and July 2014, 16 patients with 17 traumatic CCFs were embolized with the so-called ‘armored concrete’ treatment modality using coils, Onyx-18, and a non-detachable balloon via the transarterial approach. The outcomes were assessed both clinically and radiologically. Digital subtraction angiography (DSA) follow-up was performed 3 or 6 months after endovascular treatment while clinical follow-up was continued until December 2014.ResultsObliteration of the CCFs was obtained with patency of the parent artery in all 16 cases. Follow-up DSA demonstrated stable occlusion of all the fistulas. Symptoms related to the CCFs were either resolved immediately or gradually over 2 months. No worsening of the cranial neuropathies was observed during the follow-up period which averaged 32.6 months.ConclusionsThe ‘armored concrete’ treatment modality using coils, Onyx, and a non-detachable balloon promises to be a safe, economical, and effective alternative in the management of traumatic CCFs.

Clear cell renal cell carcinoma (ccRCC) is the prominent histological subtype of renal cell carcinoma (RCC) with high incidence of local recurrence and distant metastasis. It has been documented that circular ribonucleic acids (circRNAs) play crucial roles in the development of cancers; however, study on exploring the role of circRNAs in ccRCC still remains limited. In the present study, we aimed to evaluate the biological function of a novel circRNA UBAP2 (circUBAP2) in ccRCC and the underlying mechanism. Our results showed that circUBAP2 expression was significantly down-regulated in ccRCC tissues and cell lines. Overexpression of circUBAP2 significantly inhibited the proliferation, migration, and invasion of ccRCC cells. MiR-148a-3p was a target miRNA of circUBAP2 in ccRCC cells, and its expression levels in ccRCC tissues and cell lines were negatively correlated with circUBAP2 levels. Moreover, miR-148a-3p reversed the inhibitory effects of circUBAP2 on cell proliferation, migration, and invasion in ccRCC cells. Additionally, forkhead box K2 (FOXK2) was found to be a target gene of miR-148a-3p and regulated by miR-148a-3p in ccRCC cells. Furthermore, knockdown of FOXK2 reversed the inhibitory effects of miR-148a-3p inhibitor on ccRCC cells. In conclusion, these findings indicated that circUBAP2 functioned as a novel tumor suppressor in ccRCC through regulating the miR-148a-3p/FOXK2 axis. Therefore, circUBAP2 might serve as a potential therapeutic target for the treatment of ccRCC.