IL-13 secreted by ILC2s promotes the self-renewal of intestinal stem cells through circular RNA circPan3.

Intestinal stem cells (ISCs) are maintained by stemness signaling for precise modulation of self-renewal and differentiation under homeostasis. However, the way in which intestinal immune cells regulate the self-renewal of ISCs remains elusive. Here we found that mouse and human Lgr5+ ISCs showed high expression of the immune cell-associated circular RNA circPan3 (originating from the Pan3 gene transcript). Deletion of circPan3 in Lgr5+ ISCs impaired their self-renewal capacity and the regeneration of gut epithelium in a manner dependent on immune cells. circPan3 bound mRNA encoding the cytokine IL-13 receptor subunit IL-13Rα1 (Il13ra1) in ISCs to increase its stability, which led to the expression of IL-13Rα1 in ISCs. IL-13 produced by group 2 innate lymphoid cells in the crypt niche engaged IL-13Rα1 on crypt ISCs and activated signaling mediated by IL-13‒IL-13R, which in turn initiated expression of the transcription factor Foxp1. Foxp1 is associated with ß-catenin in rendering its nuclear translocation, which caused activation of the ß-catenin pathway and the maintenance of Lgr5+ ISCs.

The chromatin remodeler SRCAP promotes self-renewal of intestinal stem cells.

Lgr5+ intestinal stem cells (ISCs) exhibit self-renewal and differentiation features under homeostatic conditions, but the mechanisms controlling Lgr5 + ISC self-renewal remain elusive. Here, we show that the chromatin remodeler SRCAP is highly expressed in mouse intestinal epithelium and ISCs. Srcap deletion impairs both self-renewal of ISCs and intestinal epithelial regeneration. Mechanistically, SRCAP recruits the transcriptional regulator REST to the Prdm16 promoter and induces expression of this transcription factor. By activating PPARδ expression, Prdm16 in turn initiates PPARδ signaling, which sustains ISC stemness. Rest or Prdm16 deficiency abrogates the self-renewal capacity of ISCs as well as intestinal epithelial regeneration. Collectively, these data show that the SRCAP-REST-Prdm16-PPARδ axis is required for self-renewal maintenance of Lgr5 + ISCs.

Integrating Recombinase Polymerase Amplification and Photosensitization Colorimetric Detection in One Tube for Fast Screening of C. sakazakii in Formula Milk Powder.

Cronobacter sakazakii (C. sakazakii) is a widely existing opportunistic pathogen and thus threatens people with low immunity, especially infants. To prevent the outbreak, a rapid and accurate on-site testing method is required. The current standard culture-based method is time-consuming (3-4 days), while the nucleic acid amplification (PCR)-based detection is mostly carried out in central laboratories. Herein, isothermal recombinase polymerase amplification (RPA) coupled with a photosensitization colorimetric assay (PCA) was adopted for the on-site detection of C. sakazakii in powdered infant formulas (PIFs). The lowest visual detection concentration of C. sakazakii is 800 cfu/mL and 2 cfu/g after 8 h bacteria pre-enrichment. Furthermore, to avoid typical cap opening-resulted aerosol pollution, the PCA reagents were lyophilized onto the cap of the RPA tube (containing lyophilized RPA reagents). After amplification, the tube was subjected to simple shaking to mix the PCA reagents with the amplification products for light-driven color development. Such a one-tube assay offered a lowest concentration of 1000 copies of genomic DNA of C. sakazakii within 1 h. After 8 h of bacterial enrichment, the lowest detecting concentration could be pushed down to 5 cfu/g bacteria in PIF. To facilitate on-site monitoring, a portable, battery-powered PCA device was designed to mount the typical RPA 8-tube strip, and a color analysis cellphone APP was further employed for facile readout.

Spontaneous Formation of Ultrasmall Noble Metal Nanoparticles on Cobalt-Based Layered Double Hydroxide for Electrochemical and Environmental Catalysis.

Supported noble metal nanoparticles (NMNPs) are appealing for energy and environment catalysis. To facilitate the loading of NMNPs, in situ reduction of Mn+ on the support with extra reductants/surfactants is adopted, but typically results in aggregated NMNPs with uneven size distributions or blocked active sites of the NMNPs. Herein, the use of cobalt layered double hydroxide (Co-LDH) is proposed as both support and reductant for the preparation of supported NMNPs with ultrasmall sizes and even distributions. The resultant Co-LDH-supported NMNPs exhibit excellent catalytic performance and stability. For example, Ir/Co-LDH displays a low overpotential of 188 mV (10 mA cm-2) for electrocatalytic oxygen evolution reaction and a long-term stability over 100 h (100 mA cm-2) in overall water splitting. Ru/Co-LDH can achieve a 4-nitrophenol reduction with high rate of 0.36 min-1 and S2- detection with low limit of detection (LOD) of 0.34 µm. Overall, this work provides a green and effective strategy to fabricate supported NMNPs with greatly improved catalytic performances.

Multi-Enzyme Activity of MIL-101 (Fe)-Derived Cascade Nano-Enzymes for Antitumor and Antimicrobial Therapy.

The clinical application of oncology therapy is hampered by high glutathione concentrations, hypoxia, and inefficient activation of cell death mechanisms in cancer cells. In this study, Fe and Mo bimetallic sulfide nanomaterial (FeS2@MoS2) based on metal-organic framework structure is rationally prepared with peroxidase (POD)-, catalase (CAT)-, superoxide dismutase (SOD)-like activities and glutathione depletion ability, which can confer versatility for treating tumors and mending wounds. In the lesion area, FeS2@MoS2 with SOD-like activity can facilitate the transformation of superoxide anions (O2 -) to hydrogen peroxide (H2O2), and then the resulting H2O2 serves as a substrate for the Fenton reaction with FMS to produce highly toxic hydroxyl radicals (∙OH). Simultaneously, FeS2@MoS2 has an ability to deplete glutathione (GSH) and catalyze the decomposition of nicotinamide adenine dinucleotide phosphate (NADPH) to curb the regeneration of GSH from the source. Thus it can realize effective tumor elimination through synergistic apoptosis-ferroptosis strategy. Based on the alteration of the H2O2 system, free radical production, glutathione depletion and the alleviation of hypoxia in the tumor microenvironment, FeS2@MoS2 NPS can not only significantly inhibit tumors in vivo and in vitro, but also inhibit multidrug-resistant bacteria and hasten wound healing. It may open the door to the development of cascade nanoplatforms for effective tumor treatment and overcoming wound infection.

Hollow CoZnSe@CN nanocage with enzymatic activity for determination of tetracycline using smartphone platforms and virtual reality revealing.

Antibiotic residues in the environment pose a serious threat to ecosystems and human health. Therefore, it is important to develop sensitive and rapid in situ detection methods. In this work, the designed nanozymes, with excellent four enzyme activities, were proved to be constituted of unique hollow nanocage structures (CoZnSe@CN HCs). Based on the peroxidase-like enzymes, a portable colorimetric sensor was constructed for the on-site determination of tetracycline (TC) in real samples. The linear range of TC detection was 0.1-100 µM, and the detection limit was 0.02 µM. At the same time, colorimetric detection and smartphones have also been combined for on-site colorimetric detection of TC. In-depth exploration of the detection mechanism showed that TC could be bound with the material, inhibiting the production of oxidized 3,3',5,5'-tetramethylbenzidine. The sensor was also used for the detection of TC in environmental soil and water samples. This study can provide an intelligent detection method for environmental monitoring.

LncRNA HAND2-AS1 promotes liver cancer stem cell self-renewal via BMP signaling.

Hepatocellular carcinoma (HCC) is the most prevalent liver cancer, characterized by a high rate of recurrence and heterogeneity. Liver cancer stem cells (CSCs) may well contribute to both of these pathological properties, but the mechanism underlying their self-renewal maintenance is poorly understood. Here, we identified a long noncoding RNA (lncRNA) termed HAND2-AS1 that is highly expressed in liver CSCs. Human HAND2-AS1 and its mouse ortholog lncHand2 display a high level of conservation. HAND2-AS1 is required for the self-renewal maintenance of liver CSCs to initiate HCC development. Mechanistically, HAND2-AS1 recruits the INO80 chromatin-remodeling complex to the promoter of BMPR1A, thereby inducing its expression and leading to the activation of BMP signaling. Importantly, interfering with expression of HAND2-AS1 by antisense oligonucleotides (ASOs) and BMPR1A by siRNAs has synergistic anti-tumorigenic effects on humanized HCC models. Moreover, knockout of lncHand2 or Bmpr1a in mouse hepatocytes impairs BMP signaling and suppresses the initiation of liver cancer. Our findings reveal that HAND2-AS1 promotes the self-renewal of liver CSCs and drives liver oncogenesis, offering a potential new target for HCC therapy.

Selective Heavy Atom Effect-Promoted Photosensitization Colorimetric Detection of Ag+ in Silver Ore Samples.

Analytical methods capable of facile screening of silver ore samples are of vital importance for resource exploration and ore mining. Due to its extreme simplicity, colorimetric detection is desired for silver ore screening, but the analytical sensitivity of existing approaches is typically not sufficient. Here, an Ag+-selective heavy atom effect-promoted photosensitization colorimetric assay was developed. Specifically, Ag+ and dsDNA-staining dye (photosensitizer) were spatially adjoined in close proximity in dsDNA bearing several cytosine (C) mismatches, leading to enhanced 1O2 generation for photosensitized oxidation of chromogenic substrate 3,3',5,5'-tetramethylbenzidine (TMB). Due to the stable C-Ag(I)-C metallo-base pair, the C-C mismatches in dsDNA can selectively capture Ag+, thus allowing highly selective colorimetric detection of Ag+ with a visual limit of quantification (LOQ) as low as 0.2 ng/mL. For ore sample analysis, the visual LOQ was about 2 g/t, which was suitable for colorimetric screening analysis of ores of different values. The accuracy of the proposed method was verified through analyzing both certified reference material and real ore samples, the results of which agreed well with those obtained by electrothermal atomic absorption spectrometry (ET-AAS). To facilitate field silver ore screening, acid leaching of the samples was also adopted, and satisfactory analytical accuracy was also obtained at a rough leaching efficiency of 20%.

Health Impacts of Long-Term NO2 Exposure and Inequalities among the Chinese Population from 2013 to 2020.

Nitrogen dioxide (NO2) is associated with mortality and many other adverse health outcomes. In 2021, the World Health Organization established a new NO2 air quality guideline (AQG) (annual average <10 µg/m3). However, the burden of diseases attributable to long-term NO2 exposure above the AQG is unknown in China. Nitrogen oxide is a major air pollutant in populous cities, which are disproportionately impacted by NO2; this represents a form of environmental inequality. We conducted a nationwide risk assessment of premature deaths attributable to long-term NO2 exposure from 2013 to 2020 based on the exposure-response relationship, high-resolution annual NO2 concentrations, and gridded population data (considering sex, age, and residence [urban vs rural]). We calculated health metrics including attributable deaths, years of life lost (YLL), and loss of life expectancy (LLE). Inequality in the distribution of attributable deaths and YLLs was evaluated by the Lorenz curve and Gini index. According to the health impact assessments, in 2013, long-term NO2 exposure contributed to 315,847 (95% confidence interval [CI]: 306,709-319,269) premature deaths, 7.90 (7.68-7.99) million YLLs, and an LLE of 0.51 (0.50-0.52) years. The high-risk subgroup (top 20%) accounted for 85.7% of all NO2-related deaths and 85.2% of YLLs, resulting in Gini index values of 0.81 and 0.67, respectively. From 2013 to 2020, the estimated health impact from NO2 exposure was significantly reduced, but inequality displayed a slightly increasing trend. Our study revealed a considerable burden of NO2-related deaths in China, which were disproportionally frequent in a small high-risk subgroup. Future clean air initiatives should focus not only on reducing the average level of NO2 exposure but also minimizing inequality.

GDF11 promotes wound healing in diabetic mice via stimulating HIF-1ɑ-VEGF/SDF-1ɑ-mediated endothelial progenitor cell mobilization and neovascularization.

Non-healing diabetic wounds (DW) are a serious clinical problem that remained poorly understood. We recently found that topical application of growth differentiation factor 11 (GDF11) accelerated skin wound healing in both Type 1 DM (T1DM) and genetically engineered Type 2 diabetic db/db (T2DM) mice. In the present study, we elucidated the cellular and molecular mechanisms underlying the action of GDF11 on healing of small skin wound. Single round-shape full-thickness wound of 5-mm diameter with muscle and bone exposed was made on mouse dorsum using a sterile punch biopsy 7 days following the onset of DM. Recombinant human GDF11 (rGDF11, 50 ng/mL, 10 µL) was topically applied onto the wound area twice a day until epidermal closure (maximum 14 days). Digital images of wound were obtained once a day from D0 to D14 post-wounding. We showed that topical application of GDF11 accelerated the healing of full-thickness skin wounds in both type 1 and type 2 diabetic mice, even after GDF8 (a muscle growth factor) had been silenced. At the cellular level, GDF11 significantly facilitated neovascularization to enhance regeneration of skin tissues by stimulating mobilization, migration and homing of endothelial progenitor cells (EPCs) to the wounded area. At the molecular level, GDF11 greatly increased HIF-1ɑ expression to enhance the activities of VEGF and SDF-1ɑ, thereby neovascularization. We found that endogenous GDF11 level was robustly decreased in skin tissue of diabetic wounds. The specific antibody against GDF11 or silence of GDF11 by siRNA in healthy mice mimicked the non-healing property of diabetic wound. Thus, we demonstrate that GDF11 promotes diabetic wound healing via stimulating endothelial progenitor cells mobilization and neovascularization mediated by HIF-1ɑ-VEGF/SDF-1ɑ pathway. Our results support the potential of GDF11 as a therapeutic agent for non-healing DW.

Xenogeneic collagen matrix versus free gingival graft for augmenting keratinized mucosa around posterior mandibular implants: a randomized clinical trial.

OBJECTIVES: To assess the clinical efficacy of xenogeneic collagen matrix (XCM) plus apically positioned flap (APF) in augmenting the keratinized mucosa (KM) width (KMW) and thickness (KMT) around posterior mandibular implants and compare it with free gingival graft (FGG) plus APF. MATERIAL AND METHODS: Thirty patients with KMW ≤ 2 mm in the posterior mandibular implant site were randomly allocated to the FGG group (FGG plus APF) or the XCM group (XCM plus APF). Clinical assessments, including KMW and KMT, shrinkage rate of established KM, and peri-implant soft tissue health, were evaluated during a 6-month follow-up. Additionally, the esthetic outcomes and patient-reported postoperative morbidity were investigated. RESULTS: At 6 months, the KMW measured 3.60 ± 0.79 mm in the FGG group and 3.28 ± 0.96 mm in the XCM group (p = 0.186). Both groups showed a tendency for graft contraction (FGG, 42.11%; XCM, 53.22%). The KMT measured 1.24 ± 0.34 mm in the FGG group and 0.95 ± 0.29 mm in the XCM group, with statistical difference (p = 0.002). No difference in the peri-implant soft tissue health was observed between the two groups (p > 0.05), but the esthetic outcomes were better in the XCM group (p < 0.05). CONCLUSIONS: XCM plus APF rendered a similar clinical efficacy in augmenting KMW as that with FGG plus APF, but with higher shrinkage. XCM plus APF was inferior with respect to FGG plus APF in augmenting KMT. The esthetic outcomes were better with XCM plus APF than FGG plus APF. Clinical relevance XCM plus APF graft was inferior with respect to FGG plus APF in augmenting KMT. TRIAL REGISTRATION: Trial registration number: ChiCTR2200058027 and date: 03/27/2022.

The Signaling Pathways Induced by Exosomes in Promoting Diabetic Wound Healing: A Mini-Review.

Impaired healing of diabetic wounds harms patients' quality of life and even leads to disability and death, which is an urgent issue to be solved clinically. Despite the great progress that has been achieved, it remains a worldwide challenge to develop effective therapeutic treatments for diabetic wounds. Recently, exosomes have attracted special attention because they can be involved in immune response, antigen presentation, cell migration, cell differentiation, tumor invasion and other processes. Meanwhile, exosomes have been proven to hold great potential in the treatment of diabetic wounds. Mechanistic studies of exosomes based on signaling pathways could not only help to uncover the mechanisms by which exosomes promote diabetic wound healing but could also provide a theoretical basis for the clinical application of exosomes. Herein, our mini-review aims to summarize the progress of research on the use of various exosomes derived from different cell types to promote diabetic wound healing, with a focus on the classical signaling pathways, including PI3K/Akt, Wnt, NF-κB, MAPK, Notch, Nrf2, HIF-1α/VEGF and TGF-ß/Smad. The results show that exosomes could regulate these signaling pathways to down-regulate inflammation, reduce oxidative stress, increase angiogenesis, promote fibroblast proliferation, induce re-epithelization and inhibit scar formation, making exosomes attractive candidates for the treatment of diabetic wounds.

LncKdm2b controls self-renewal of embryonic stem cells via activating expression of transcription factor Zbtb3.

Divergent long noncoding RNAs (lncRNAs) represent a major lncRNA biotype in mouse and human genomes. The biological and molecular functions of the divergent lncRNAs remain largely unknown. Here, we show that lncKdm2b, a divergent lncRNA for Kdm2b gene, is conserved among five mammalian species and highly expressed in embryonic stem cells (ESCs) and early embryos. LncKdm2b knockout impairs ESC self-renewal and causes early embryonic lethality. LncKdm2b can activate Zbtb3 by promoting the assembly and ATPase activity of Snf2-related CREBBP activator protein (SRCAP) complex in trans Zbtb3 potentiates the ESC self-renewal in a Nanog-dependent manner. Finally, Zbtb3 deficiency impairs the ESC self-renewal and early embryonic development. Therefore, our findings reveal that lncRNAs may represent an additional layer of the regulation of ESC self-renewal and early embryogenesis.

Near-Infrared in and out: Observation of Autophagy during Stroke via a Lysosome-Targeting Two-Photon Viscosity-Dependent Probe.

Fluorescence imaging using probes with two-photon excitation and near-infrared emission is currently the most popular in situ method for monitoring biological species or events, with a large imaging depth, low background fluorescence, low optical damage, and high spatial and temporal resolution. Nevertheless, current fluorescent dyes with near-infrared emission still have some disadvantages such as poor water solubility, low fluorescence quantum yield, and small two-photon absorption cross sections. These drawbacks are mainly caused by the structural characteristics of dyes with large conjugation surfaces but lacking strong and rigid structures. Herein, a lysosome-targeted and viscosity-sensitive probe (NCIC-VIS) is designed and synthesized. The protonation of morpholine not only helps anchor NCIC-VIS to the lysosome but also significantly enhances its water solubility. More importantly, its viscosity can increase the rigid structure of NCIC-VIS, which will improve the fluorescence quantum yield and the two-photon absorption cross section due to the imposed restrictions on molecular torsion. Based on the abovementioned characteristics, the real-time imaging of cellular autophagy (could increase the viscosity of lysosomes) was realized using NCIC-VIS. The results demonstrated that the level of autophagy was significantly enhanced in mice during stroke, while the inhibition of oxidative stress significantly reduced the degree of autophagy. The study corroborates that oxidative stress induced by stroke can lead to the development of autophagy.

Signal-On Near-Infrared Photoelectrochemical Aptasensors for Sensing VEGF165 Based on Ionic Liquid-Functionalized Nd-MOF Nanorods and In-Site Formation of Gold Nanoparticles.

The low photon energy and deep penetrating ability of near-infrared (NIR) light make it an ideal light source for a photoelectrochemical (PEC) immunosensing system. Absorption wavelengths of the metal-organic frameworks (MOFs) can be regulated by adjusting the metal ions and the conjugation degree of the ligands. Herein, an ionic liquid with a large conjugated structure was synthesized and was used as a ligand to coordinate with Nd ions to prepare Nd-MOF nanorods with a band gap of 1.26 eV. The Nd-MOF rods show a good photoabsorption property from 200 to 980 nm. A PEC platform was constructed by using Nd-MOF nanorods as the photoelectroactive element. A detachable double-stranded DNA labeled with alkaline phosphatase (ALP), which is specific to VEGF165, was immobilized onto the PEC sensing interface. After blocking unspecific active sites with bovine albumin, an NIR PEC aptasensing system was developed for VEGF165 detection. After being incubated in a mixture of VEGF165, l-ascorbic acid 2-phosphate (magnesium salt hydrate) (AAP), and chloroauric acid, the aptamers for VEGF165 were detached from the PEC aptasensing interface, thus resulting in the decrease of the charge-transfer resistance and the increase of the photocurrent response. The shedding of the aptamers also makes the ALP approach the electrode surface, thus catalyzing the reduction of AAP to produce ascorbic acid (AA). Subsequently, AA reduces in situ chloroauric acid to produce AuNPs on the Nd-MOF-based sensing interface. With the excellent conductivity and localized surface plasmon resonance effect, the AuNPs can accelerate the separation of electron-hole pairs generated from Nd-MOF nanorods, thus promoting the photoelectric conversion efficiency and achieving signal amplification. Under optimized conditions, the PEC responses were linearly related to the VEGF165 concentrations in the range of 0.01-100 ng mL-1 and exhibit a low detection limit of 3.51 pg mL-1 (S/N = 3). VEGF165 in human serum samples was detected by the NIR PEC aptasensor. Their concentrations were found to be well consistent with that obtained from ELISA. Furthermore, the PEC aptasensor demonstrated recoveries from 96.07 to 103.8%. The relative standard deviations were within 5%, indicating good accuracy and precision. The results further verify its practicability for clinical diagnosis.

Inflammation-Stimulated MSC-Derived Small Extracellular Vesicle miR-27b-3p Regulates Macrophages by Targeting CSF-1 to Promote Temporomandibular Joint Condylar Regeneration.

Small extracellular vesicles (sEVs) secreted by mesenchymal stem cells (MSCs) have been extensively studied in recent years. sEV contents change with the secreting cell state. When MSCs are exposed to an inflammatory environment, they release more functional growth factors, exosomes, and chemokines. Herein, MSCs are stimulated to alter sEV cargos and functions to regulate the inflammatory microenvironment and promote tissue regeneration. Sequencing of sEV miRNAs shows that certain RNAs conducive to cell function are upregulated. In this study, in vitro cell function experiments show that both inflammation-stimulated adipose-derived MSC (ADSC)-derived sEV (IAE) and normal ADSC-derived sEV (AE) promote cell proliferation; IAE also significantly improves cell migration. Regarding macrophage polarization regulation, IAE significantly promotes M2 macrophage differentiation. RNA-sequencing analysis indicates that high miR-27b-3p expression levels in IAE may regulate macrophages by targeting macrophage colony-stimulating factor-1 (CSF-1). In vivo, a rabbit temporomandibular joint (TMJ) condylar osteochondral defect model shows that both AE and IAE promote TMJ regeneration, with IAE having the most significant therapeutic effect. Therefore, the authors confirm that exposing MSCs to an inflammatory environment can feasibly enhance sEV functions and that modified sEVs achieve better therapeutic effects.

Cation-Deficiency-Dependent CO2 Electroreduction over Copper-Based Ruddlesden-Popper Perovskite Oxides.

We report an effective strategy to enhance CO2 electroreduction (CER) properties of Cu-based Ruddlesden-Popper (RP) perovskite oxides by engineering their A-site cation deficiencies. With La2-x CuO4-δ (L2-x C, x=0, 0.1, 0.2, and 0.3) as proof-of-concept catalysts, we demonstrate that their CER activity and selectivity (to C2+ or CH4 ) show either a volcano-type or an inverted volcano-type dependence on the x values, with the extreme point at x=0.1. Among them, at -1.4 V, the L1.9 C delivers the optimal activity (51.3 mA cm-2 ) and selectivity (41.5 %) for C2+ , comparable to or better than those of most reported Cu-based oxides, while the L1.7 C exhibits the best activity (25.1 mA cm-2 ) and selectivity (22.1 %) for CH4 . Such optimized CER properties could be ascribed to the favorable merits brought by the cation-deficiency-induced oxygen vacancies and/or CuO/RP hybrids, including the facilitated adsorption/activation of key reaction species and thus the manipulated reaction pathways.

Circular RNA circIPO11 drives self-renewal of liver cancer initiating cells via Hedgehog signaling.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most intractable tumors in the world due to its high rate of recurrence and heterogeneity. Liver cancer initiating cells also called cancer stem cells (CSCs) play a critical role in resistance against typical therapy and high tumor-initiating potential. However, the role of the novel circular RNA (circRNA) circIPO11 in the maintenance of liver cancer initiating cells remains elusive. METHODS: CircRNAs highly conserved in humans and mice were identified from 3 primary HCC samples by circRNA array. The expression and function of circIPO11 were further evaluated by Northern blot, limiting dilution xenograft analysis, chromatin isolation by RNA purification-PCR assay (ChIRP) and HCC patient-derived tumor cells (PDC) models. CircIpo11 knockout (KO) mice were generated by a CRISPR/Cas9 technology. RESULTS: CircIPO11 is highly expressed in HCC tumor tissues and liver CSCs. CircIPO11 is required for the self-renewal maintenance of liver CSCs to initiate HCC development. Mechanistically, circIPO11 recruits TOP1 to GLI1 promoter to trigger its transcription, leading to the activation of Hedgehog signaling. Moreover, GLI1 is also highly expressed in HCC tumor tissues and liver CSCs, and TOP1 expression levels positively correlate with the metastasis, recurrence and survival of HCC patients. Additionally, circIPO11 knockout in mice suppresses the progression of chemically induced liver cancer development. CONCLUSION: Our findings reveal that circIPO11 drives the self-renewal of liver CSCs and promotes the propagation of HCC via activating Hedgehog signaling pathway. Antisense oligonucleotides (ASOs) against circIPO11 combined with TOP1 inhibitor camptothecin (CPT) exert synergistic antitumor effect. Therefore, circIPO11 and the Hedgehog signaling pathway may provide new potential targets for the treatment of HCC patients.

Electrocatalytic, Kinetic, and Mechanism Insights into the Oxygen-Reduction Catalyzed Based on the Biomass-Derived FeOx @N-Doped Porous Carbon Composites.

A valid strategy for amplifying the oxygen reduction reaction (ORR) efficiency of non-noble electrocatalyst in both alkaline and acid electrolytes by decorated with a layer of biomass derivative nitrogen-doped carbon (NPC) is proposed. Herein, a top-down strategy for the generally fabricating NPC matrix decorated with trace of metal oxides nanoparticles (FeOx NPs) by a dual-template assisted high-temperature pyrolysis process is reported. A high-activity FeOx /FeNC (namely Hemin/NPC-900) ORR electrocatalyst is prepared via simply carbonizing the admixture of Mg5 (OH)2 (CO3 )4 and NaCl as dual-templates, melamine and acorn shells as nitrogen and carbon source, hemin as a natural iron and nitrogen source, respectively. Owing to its unique 3D porous construction, large BET areas (819.1 m2 ∙g-1 ), and evenly dispersed active sites (FeNx , CN, and FeO parts), the optimized Hemin/NPC-900 catalyst displays comparable ORR catalytic activities, remarkable survivability to methanol, and preferable long-term stability in both alkali and acid electrolyte compared with benchmark Pt/C. More importantly, density function theory computations certify that the interaction between Fe3 O4 nanoparticles and arm-GN (graphitic N at armchair edge) active sites can effectually promote ORR electrocatalytic performance by a lower overpotential of 0.81 eV. Accordingly, the research provides some insight into design of low-cost non-precious metal ORR catalysts in theory and practice.

CO2 Electroreduction to Formate at a Partial Current Density up to 590 mA mg-1 via Micrometer-Scale Lateral Structuring of Bismuth Nanosheets.

2D bismuth nanosheets are a promising layered material for formate-producing via electrocatalytic CO2 conversion. However, the commercial interest of bismuth nanosheets in CO2 electroreduction is still rare due to the undesirable current density for formate at moderate operation potentials (about 200 mA mg-1 ) and harsh synthesis conditions (high temperature and/or high pressure). This work reports the preparation of Bi nanosheets with a lateral size in micrometer-scale via electrochemical cathodic exfoliation in aqueous solution at normal pressure and temperature. As-prepared Bi LNSs (L indicates large lateral size) possess high Faradaic efficiencies over 90% within a broad potential window from -0.44 to -1.10 V versus RHE and a superior partial current density about 590 mA mg-1 for formate in comparison with state-of-the-art results. Structure analysis, electrochemical results, and density functional theory calculations demonstrate that the increasing tensile lattice strain observed in Bi LNSs leads to less overlap of d orbitals and a narrower d-band width, which tuning the intermediate binding energies, and therefore promotes the intrinsic activity.