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TAX1BP1, a multifunctional autophagy adaptor, plays critical roles in different autophagy processes. As an autophagy receptor, TAX1BP1 can interact with RB1CC1, NAP1, and mammalian ATG8 family proteins to drive selective autophagy for relevant substrates. However, the mechanistic bases underpinning the specific interactions of TAX1BP1 with RB1CC1 and mammalian ATG8 family proteins remain elusive. Here, we find that there are two distinct binding sites between TAX1BP1 and RB1CC1. In addition to the previously reported TAX1BP1 SKICH (skeletal muscle and kidney enriched inositol phosphatase (SKIP) carboxyl homology)/RB1CC1 coiled-coil interaction, the first coiled-coil domain of TAX1BP1 can directly bind to the extreme C-terminal coiled-coil and Claw region of RB1CC1. We determine the crystal structure of the TAX1BP1 SKICH/RB1CC1 coiled-coil complex and unravel the detailed binding mechanism of TAX1BP1 SKICH with RB1CC1. Moreover, we demonstrate that RB1CC1 and NAP1 are competitive in binding to the TAX1BP1 SKICH domain, but the presence of NAP1's FIP200-interacting region (FIR) motif can stabilize the ternary TAX1BP1/NAP1/RB1CC1 complex formation. Finally, we elucidate the molecular mechanism governing the selective interactions of TAX1BP1 with ATG8 family members by solving the structure of GABARAP in complex with the non-canonical LIR (LC3-interacting region) motif of TAX1BP1, which unveils a unique binding mode between LIR and ATG8 family protein. Collectively, our findings provide mechanistic insights into the interactions of TAX1BP1 with RB1CC1 and mammalian ATG8 family proteins and are valuable for further understanding the working mode and function of TAX1BP1 in autophagy.
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Autofagia , Proteínas de Ciclo Celular , Animales , Familia de las Proteínas 8 Relacionadas con la Autofagia , Sitios de Unión , Riñón , MamíferosRESUMEN
Pyroptosis, a pro-inflammatory programmed cell death, has been implicated in the pathogenesis of coronavirus disease 2019 and other viral diseases. Gasdermin family proteins (GSDMs), including GSDMD and GSDME, are key regulators of pyroptotic cell death. However, the mechanisms by which virus infection modulates pyroptosis remain unclear. Here, we employed a mCherry-GSDMD fluorescent reporter assay to screen for viral proteins that impede the localization and function of GSDMD in living cells. Our data indicated that the main protease NSP5 of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) blocked GSDMD-mediated pyroptosis via cleaving residues Q29 and Q193 of GSDMD. While another SARS-CoV-2 protease, NSP3, cleaved GSDME at residue G370 but activated GSDME-mediated pyroptosis. Interestingly, respiratory enterovirus EV-D68-encoded proteases 3C and 2A also exhibit similar differential regulation on the functions of GSDMs by inactivating GSDMD but initiating GSDME-mediated pyroptosis. EV-D68 infection exerted oncolytic effects on human cancer cells by inducing pyroptotic cell death. Our findings provide insights into how respiratory viruses manipulate host cell pyroptosis and suggest potential targets for antiviral therapy as well as cancer treatment.IMPORTANCEPyroptosis plays a crucial role in the pathogenesis of coronavirus disease 2019, and comprehending its function may facilitate the development of novel therapeutic strategies. This study aims to explore how viral-encoded proteases modulate pyroptosis. We investigated the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and respiratory enterovirus D68 (EV-D68) proteases on host cell pyroptosis. We found that SARS-CoV-2-encoded proteases NSP5 and NSP3 inactivate gasdermin D (GSDMD) but initiate gasdermin E (GSDME)-mediated pyroptosis, respectively. We also discovered that another respiratory virus EV-D68 encodes two distinct proteases 2A and 3C that selectively trigger GSDME-mediated pyroptosis while suppressing the function of GSDMD. Based on these findings, we further noted that EV-D68 infection triggers pyroptosis and produces oncolytic effects in human carcinoma cells. Our study provides new insights into the molecular mechanisms underlying virus-modulated pyroptosis and identifies potential targets for the development of antiviral and cancer therapeutics.
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Endopeptidasas , Enterovirus Humano D , Interacciones Microbiota-Huesped , Virus Oncolíticos , Piroptosis , SARS-CoV-2 , Humanos , Línea Celular Tumoral , COVID-19/metabolismo , COVID-19/terapia , COVID-19/virología , Endopeptidasas/genética , Endopeptidasas/metabolismo , Enterovirus Humano D/enzimología , Enterovirus Humano D/genética , Infecciones por Enterovirus/metabolismo , Infecciones por Enterovirus/virología , Gasderminas/antagonistas & inhibidores , Gasderminas/genética , Gasderminas/metabolismo , Viroterapia Oncolítica , Virus Oncolíticos/enzimología , Virus Oncolíticos/genética , SARS-CoV-2/enzimología , SARS-CoV-2/genética , Proteínas Virales/genética , Proteínas Virales/metabolismoRESUMEN
Shigella flexneri, a gram-negative bacterium, is the major culprit of bacterial shigellosis and causes a large number of human infection cases and deaths worldwide annually. For evading the host immune response during infection, S. flexneri secrets two highly similar E3 ligases, IpaH1.4 and IpaH2.5, to subvert the linear ubiquitin chain assembly complex (LUBAC) of host cells, which is composed of HOIP, HOIL-1L, and SHARPIN. However, the detailed molecular mechanism underpinning the subversion of the LUBAC by IpaH1.4/2.5 remains elusive. Here, we demonstrated that IpaH1.4 can specifically recognize HOIP and HOIL-1L through its leucine-rich repeat (LRR) domain by binding to the HOIP RING1 domain and HOIL-1L ubiquitin-like (UBL) domain, respectively. The determined crystal structures of IpaH1.4 LRR/HOIP RING1, IpaH1.4 LRR/HOIL-1L UBL, and HOIP RING1/UBE2L3 complexes not only elucidate the binding mechanisms of IpaH1.4 with HOIP and HOIL-1L but also unveil that the recognition of HOIP by IpaH1.4 can inhibit the E2 binding of HOIP. Furthermore, we demonstrated that the interaction of IpaH1.4 LRR with HOIP RING1 or HOIL-1L UBL is essential for the ubiquitination of HOIP or HOIL-1L in vitro as well as the suppression of NF-κB activation by IpaH1.4 in cells. In summary, our work elucidated that in addition to inducing the proteasomal degradation of LUBAC, IpaH1.4 can also inhibit the E3 activity of LUBAC by blocking its E2 loading and/or disturbing its stability, thereby providing a paradigm showing how a bacterial E3 ligase adopts multiple tactics to subvert the key LUBAC of host cells.
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Shigella flexneri , Ubiquitina-Proteína Ligasas , Humanos , FN-kappa B/metabolismo , Shigella flexneri/genética , Shigella flexneri/metabolismo , Transducción de Señal , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , UbiquitinaciónRESUMEN
To ensure the safety of drinking water, ozone (O3) has been extensively applied in drinking water treatment plants to further remove natural organic matter (NOM). However, the surface water and groundwater near the coastal areas often contain high concentrations of bromide ion (Br-). Considering the risk of bromate (BrO3-) formation in ozonation of the sand-filtered water, the inhibitory efficiencies of hydrogen peroxide (H2O2) and ammonia (NH3) on BrO3- formation during ozonation process were compared. The addition of H2O2 effectively inhibited BrO3- formation at an initial Br- concentration amended to 350 µg/L. The inhibition efficiencies reached 59.6 and 100% when the mass ratio of H2O2/O3 was 0.25 and > 0.5, respectively. The UV254 and total organic carbon (TOC) also decreased after adding H2O2, while the formation potential of trihalomethanes (THMsFP) increased especially in subsequent chlorination process at a low dose of H2O2. To control the formation of both BrO3- and THMs, a relatively large dose of O3 and a high ratio of H2O2/O3were generally needed. NH3 addition inhibited BrO3- formation when the background ammonia nitrogen (NH3N) concentration was low. There was no significant correlation between BrO3- inhibition efficiency and NH3 dose, and a small amount of NH3N (0.2 mg/L) could obviously inhibit BrO3- formation. The oxidation of NOM seemed unaffected by NH3 addition, and the structure of NOM reflected by synchronous fluorescence (SF) scanning remained almost unchanged before and after adding NH3. Considering the formation of BrO3- and THMs, the optimal dose of NH3 was suggested to be 0.5 mg/L.
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Ozono , Contaminantes Químicos del Agua , Purificación del Agua , Amoníaco , Bromatos , Bromuros , Peróxido de Hidrógeno , Trihalometanos , Agua , Contaminantes Químicos del Agua/análisisRESUMEN
Molybdenum disulfide (MoS2), as a typical layered transition metal sulfide, has been widely used in photocatalysis. Here, we report layered MoS2 nanosheet-coated TiO2 heterostructures that were prepared using a simple photo-assisted deposition method. The as-prepared samples were investigated in detail by using X-ray diffraction, Raman spectroscopy, scanning electron microscopy, transmission electron microscopy, and X-ray photoelectron spectroscopy. Results demonstrated that the MoS2 nanosheets uniformly covered the outer surface of TiO2. The visible light-sensitive photocatalytic activity was evaluated by the removal of methylene blue (MB) and 2-chlorophenol (2-CP) in aqueous solution. Thus, the MoS2/TiO2 heterostructures exhibited improved photocatalytic degradation activity under visible light compared with the pure TiO2. Under visible light irradiation for 90 min, the degradation efficiencies of MB and 2-CP over the MoS2/TiO2 sample (sunlight irradiation time: 30 min) are as high as 93.6% and 70.6%, respectively. Furthermore, the corresponding mechanism of enhanced photocatalytic activity is proposed on the basis of the comprehensively investigated results from the radical trapping experiments, photoluminescence spectroscopy, and electron spin resonance analysis. The hole oxidation, hydroxyl radicals, and superoxide anion radicals act as the active species simultaneously in the photodegradation of the dye molecules. However, of these species, hole oxidation played the most important roles in the photocatalytic reaction.
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Chondrogenesis can regulate bone formation. Fibroblast growth factor receptor 3, highly expressed in chondrocytes, is a negative regulator of bone growth. To investigate whether chondrocyte FGFR3 regulates osteogenesis, thereby contributing to postnatal bone formation and bone remodeling, mice with conditional knock-out of Fgfr3 in chondrocytes (mutant (MUT)) were generated. MUT mice displayed overgrowth of bone with lengthened growth plates. Bone mass of MUT mice was significantly increased at both 1 month and 4 months of age. Histological analysis showed that osteoblast number and bone formation were remarkably enhanced after deletion of Fgfr3 in chondrocytes. Chondrocyte-osteoblast co-culture assay further revealed that Fgfr3 deficiency in chondrocytes promoted differentiation and mineralization of osteoblasts by up-regulating the expressions of Ihh, Bmp2, Bmp4, Bmp7, Wnt4, and Tgf-ß1, as well as down-regulating Nog expression. In addition, osteoclastogenesis was also impaired in MUT mice with decreased number of osteoclasts lining trabecular bone, which may be related to the reduced ratio of Rankl to Opg in Fgfr3-deficient chondrocytes. This study reveals that chondrocyte FGFR3 is involved in the regulation of bone formation and bone remodeling by a paracrine mechanism.
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Condrocitos/metabolismo , Placa de Crecimiento/metabolismo , Osteogénesis/fisiología , Osteoprotegerina/biosíntesis , Comunicación Paracrina/fisiología , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/biosíntesis , Animales , Proteínas Morfogenéticas Óseas/biosíntesis , Proteínas Morfogenéticas Óseas/genética , Remodelación Ósea/fisiología , Células Cultivadas , Condrocitos/citología , Técnicas de Cocultivo , Placa de Crecimiento/citología , Ratones , Ratones Noqueados , Tamaño de los Órganos/fisiología , Osteoblastos/citología , Osteoblastos/metabolismo , Osteoclastos/citología , Osteoclastos/metabolismo , Osteoprotegerina/genética , Ligando RANK/biosíntesis , Ligando RANK/genética , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/genética , Factor de Crecimiento Transformador beta1/genética , Proteína Wnt4/biosíntesis , Proteína Wnt4/genéticaRESUMEN
BACKGROUND: Long-term administration of α-lipoic acid (α-LA) is proved to ameliorate renal impairment. Herein we assessed serum, urinary biomarkers and vascular endothelium function to evaluate its short-period therapeutic effect and identify novel biomarkers for diabetic nephropathy (DN). METHODS: Sixty-two microalbuminuria-stage DN patients were randomly divided into two groups and received the following treatment for 8 weeks: (1) routine treatment(DM group); (2) routine treatment with 600 mg/d α-lipoic acid intravenously (α-LA group). Another total of 21 patients were recruited for the second-stage study and randomly divided into two groups: normoalbuminuria (UAER <30 mg/24 h) and microalbuminuria (UAER from 30-300 mg/24 h). RESULTS: With α-LA treatment, urinary albumin excretion rates (UAER), serum creatinine (SCr) and malonaldehyde (MDA) declined significantly, whereas plasma superoxide dismutase (SOD)activity increased and endothelium-dependent flow mediated vasodilation (FMD) flexibility improved dramatically. Furthermore, the improvement of FMD showed positive correlation with the variation in MDA and SOD as well (r values are .516 and .435, P<.01 and P<.05, respectively). In contrast, these markers have no significant difference in the DM group with routine treatment. Notably, the CD63 expressing of exosomes in urine was found higher in the normoalbuminuria patients compared with those in microalbuminuria, parallelly only declined markedly after α-LA administration in normoalbuminuria patients. CONCLUSION: In summary, we emphasize short-term α-LA could protect the kidney in the early DN against general oxidative stress, particularly the urinary CD63-positive exosome could be a potential sensitive and therapeutic indicator.
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Biomarcadores/orina , Nefropatías Diabéticas , Exosomas/efectos de los fármacos , Sustancias Protectoras , Ácido Tióctico , Anciano , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/epidemiología , Nefropatías Diabéticas/orina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sustancias Protectoras/farmacología , Sustancias Protectoras/uso terapéutico , Ácido Tióctico/farmacología , Ácido Tióctico/uso terapéuticoRESUMEN
Magnetic carbon-based catalysts with environmental friendliness have exhibited prominent effects on advanced oxidation processes. Herein, a multi-level FeCo/N-doped carbon nanosheet (FeCo/CNS) was synthesized by facile impregnation iron-cobalt salt onto cotton and followed by confined pyrolysis. We identified excellent advantages of the modified FeCo/CNS materials: (i) The convenience of the synthesis method and (ii) The dual effect of sterilization and contaminant degradation achieved through the FeCo/CNS-activated Peroxymonosulfate (PMS). The comparative experimental showed that FeCo/CNS could provide favorable catalytic performance, completely removing bisphenol A (BPA) and tetracycline (TC) within 5 min. Moreover, the potent sterilization properties against Staphylococcus aureus and Escherichia coli were also verified. Analysis of the degradation pathway confirmed the existence of intermediates, and toxicological research demonstrated that the toxicity of the degradation intermediates of BPA gradually decreased over time. Our research provided an excellent application of FeCo/CNS in PMS oxidation and sterilization inactivation.
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Compuestos de Bencidrilo , Carbono , Compuestos de Hierro , Fenoles , Peróxidos , HierroRESUMEN
HIV-1 replication is tightly regulated in host cells, and various restriction factors have important roles in inhibiting viral replication. SAMHD1, a well-known restriction factor, suppresses HIV-1 replication by hydrolyzing intracellular dNTPs, thereby limiting the synthesis of viral cDNA in quiescent cells. In this study, we revealed an additional and distinct mechanism of SAMHD1 inhibition during the postviral cDNA synthesis stage. Using immunoprecipitation and mass spectrometry analysis, we demonstrated the interaction between SAMHD1 and MX2/MxB, an interferon-induced antiviral factor that inhibits HIV-1 cDNA nuclear import. The disruption of endogenous MX2 expression significantly weakened the ability of SAMHD1 to inhibit HIV-1. The crucial region within SAMHD1 that binds to MX2 has been identified. Notably, we found that SAMHD1 can act as a sensor that recognizes and binds to the incoming HIV-1 core, subsequently delivering it to the molecular trap formed by MX2, thereby blocking the nuclear entry of the HIV-1 core structure. SAMHD1 mutants unable to recognize the HIV-1 core showed a substantial decrease in antiviral activity. Certain mutations in HIV-1 capsids confer resistance to MX2 inhibition while maintaining susceptibility to suppression by the SAMHD1-MX2 axis. Overall, our study identifies an intriguing antiviral pattern wherein two distinct restriction factors, SAMHD1 and MX2, collaborate to establish an alternative mechanism deviating from their actions. These findings provide valuable insight into the complex immune defense networks against exogenous viral infections and have implications for the development of targeted anti-HIV therapeutics. IMPORTANCE: In contrast to most restriction factors that directly bind to viral components to exert their antiviral effects, SAMHD1, the only known deoxynucleotide triphosphate (dNTP) hydrolase in eukaryotes, indirectly inhibits viral replication in quiescent cells by reducing the pool of dNTP substrates available for viral cDNA synthesis. Our study provides a novel perspective on the antiviral functions of SAMHD1. In addition to its role in dNTP hydrolysis, SAMHD1 cooperates with MX2 to inhibit HIV-1 nuclear import. In this process, SAMHD1 acts as a sensor for incoming HIV-1 cores, detecting and binding to them, before subsequently delivering the complex to the molecular trap formed by MX2, thereby immobilizing the virus. This study not only reveals a new antiviral pathway for SAMHD1 but also identifies a unique collaboration and interaction between two distinct restriction factors, establishing a novel line of defense against HIV-1 infection, which challenges the traditional view of restriction factors acting independently. Overall, our findings further indicate the intricate complexity of the host immune defense network and provide potential targets for promoting host antiviral immune defense.
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Infecciones por VIH , VIH-1 , Proteínas de Resistencia a Mixovirus , Proteína 1 que Contiene Dominios SAM y HD , Replicación Viral , Proteína 1 que Contiene Dominios SAM y HD/metabolismo , Proteína 1 que Contiene Dominios SAM y HD/genética , Humanos , VIH-1/fisiología , VIH-1/genética , Proteínas de Resistencia a Mixovirus/metabolismo , Proteínas de Resistencia a Mixovirus/genética , Infecciones por VIH/virología , Infecciones por VIH/metabolismo , Infecciones por VIH/genética , ADN Viral/metabolismo , ADN Viral/genética , Células HEK293 , Interacciones Huésped-Patógeno , Unión ProteicaRESUMEN
The degradation kinetics of Sodium dodecylbenzene sulfonate (SDBS) surfactant in the UV/chlorine process was comprehensively investigated, and the formation of chlorinated disinfection by-products (Cl-DBPs) were determined. Results showed that the degradation of SDBS by UV, chlorine and UV/chlorine all followed pseudo-first-order kinetics. The rate constant by UV/chlorine in ultrapure water was approximately 3 times higher than the sum of those by UV and chlorine, and decreased from 0.297 to 0.063 min-1 with pH increasing from 5.0 to 9.0. Water matrices such as NO3-, HCO3- and natural organic matter (NOM) inhibited the degradation efficiency to a certain extent. The second-order rate constant of SDBS with HO⢠was determined as 2.84 × 109 M-1 s-1. Through using different probes, the main contributors to SDBS degradation were found to be UV, HO⢠and reactive chlorine species (RCS). Meanwhile, 64.0 µg L-1 trichloromethane (TCM) and 8.7 µg L-1 chloral hydrate (CH) were simultaneously formed within 30 min of UV/chlorine treatment. The concentration of total organic chlorine (TOCl) (424.0 µg L-1) was obviously higher than those of TCM and CH. In addition, 414 unknown by-products formed during UV/chlorine treatment were detected by mass spectrometry at a high confidence level, including 64 monochloro-DBPs and 2 dichloro-DBPs. Although UV/chlorine process accelerated SDBS degradation, the associated DBP formation deserves enough attention.
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Contaminantes Químicos del Agua , Purificación del Agua , Cloro/química , Desinfección , Purificación del Agua/métodos , Cinética , Tensoactivos/análisis , Halogenación , Contaminantes Químicos del Agua/análisis , Rayos Ultravioleta , Agua , SodioRESUMEN
Macroautophagy plays crucial roles in the regulation of cellular physiology and requires de novo synthesis of double-membrane autophagosomes, which relies on a specific interaction between autophagy-related 16L1 (ATG16L1) and WD repeat domain phosphoinositide-interacting protein 2b (WIPI2b). However, the molecular mechanism governing the interaction of ATG16L1 with WIPI2b remains elusive. Here, we find that ATG16L1 has two distinct binding sites for interacting with WIPI2b, the previously reported WIPI2b-binding site (WBS1) and the previously unidentified site (WBS2). We determine the crystal structures of WIPI2b with ATG16L1 WBS1 and WBS2, respectively, and elucidate the molecular mechanism underpinning the recruitment of ATG16L1 by WIPI2b. Moreover, we uncover that ATG16L1 WBS2 and its binding mode with WIPI2b is well conserved from yeast to mammals, unlike ATG16L1 WBS1. Last, our cell-based functional assays demonstrate that both ATG16L1 WBS1 and WBS2 are required for the effective autophagic flux. In conclusion, our findings provide mechanistic insights into the key ATG16L1/WIPI2b interaction in autophagy.
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Autofagosomas , Autofagia , Animales , Sitios de Unión , Fosfatidilinositoles , Saccharomyces cerevisiae , MamíferosRESUMEN
Magnetic carbon-based catalysts are promising materials for advanced oxidation processes, offering both high catalytic activity and environmental friendliness, and hold great potential in environmental remediation. In this work, Fe and Co zeolite imidazole frameworks (ZIFs) derived micron-sized magnetic porous carbon beads (MPCBs) were prepared by phase inversion and following the carbonization procedure, and the morphological and structural characteristics of the MPCBs were confirmed. The presence of pores and channels in the MPCBs provides a specific microenvironment for the for the catalysis of the core. Bisphenol A (BPA) was selected for the targeted pollutant, and the catalytic experiments confirmed that the effective catalytic activity of MPCBs in the presence of peroxymonosulfate (PMS), which could almost completely degrade BPA in 20 min with a reaction rate of 0.368 min-1. Furthermore, the MPCBs were used to effectively bacterial inactivation. Intermediate products of the BPA degradation process were validated and the toxicological studies showed a gradual decrease in toxicity, indicating effective reduction of potential hazards. The macroscopic preparation methods we developed for MPCBs that is promising for industrial applications and has the potential to cope with complex environmental remediation.
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Osteoporosis (OP) is the most common skeletal disease in middle-aged and elderly people. A comprehensive understanding of the pathogenesis of osteoporosis is important. Fibroblast growth factor receptor 1 (FGFR1) is an important molecule for skeletal development and bone remodeling. Osteocytes are the most numerous cells in bone and play critical roles in bone homeostasis, however the effect of FGFR1 on osteocytes is still unclear. To clarify the direct effects of FGFR1 on osteocytes, we conditionally deleted Fgfr1 in osteocytes with Dentin matrix protein 1 (Dmp1)-Cre. We found that mice lacking Fgfr1 in osteocytes (Fgfr1f/f;Dmp-cre, MUT) showed increased trabecular bone mass at 2 and 6 months of age, which resulted from enhanced bone formation and decreased bone resorption. Furthermore, the cortical bone was thicker in WT mice than that in MUT mice at 2 and 6 months of age. Histological analysis showed that MUT mice had a decreased number of osteocytes but an increased number of osteocyte dendrites. We further found that mice lacking Fgfr1 in osteocytes showed enhanced activation of ß-catenin signaling. The expression of sclerostin, an inhibitor of Wnt/ß-catenin signaling, was obviously decreased in MUT mice. Furthermore, we found that FGFR1 can inhibit the expression of ß-catenin and decrease the activity of ß-catenin signaling. In brief, our study showed that FGFR1 in osteocytes can regulate bone mass by regulating Wnt/ß-catenin signaling, providing genetic evidence that FGFR1 plays essential roles in osteocytes during bone remodeling and suggesting that FGFR1 is a potential therapeutic target for the prevention of bone loss.
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Osteocitos , Osteoporosis , Animales , Ratones , beta Catenina/metabolismo , Osteocitos/metabolismo , Osteoporosis/patología , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/metabolismo , Vía de Señalización WntRESUMEN
Heme-oxidized IRP2 ubiquitin ligase 1 (HOIL-1L) serves as a unique E3 ligase to catalyze the mono-ubiquitination of relevant protein or sugar substrates and plays vital roles in numerous cellular processes in mammals. However, the molecular mechanism underpinning the E3 activity of HOIL-1L and the related regulatory mechanism remain elusive. Here, we report the crystal structure of the catalytic core region of HOIL-1L and unveil the key catalytic triad residues of HOIL-1L. Moreover, we discover that HOIL-1L contains two distinct linear di-ubiquitin binding sites that can synergistically bind to linear tetra-ubiquitin, and the binding of HOIL-1L with linear tetra-ubiquitin can promote its E3 activity. The determined HOIL-1L/linear tetra-ubiquitin complex structure not only elucidates the detailed binding mechanism of HOIL-1L with linear tetra-ubiquitin but also uncovers a unique allosteric ubiquitin-binding site for the activation of HOIL-1L. In all, our findings provide mechanistic insights into the E3 activity of HOIL-1L and its regulation by the linear ubiquitin chain binding.
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Ubiquitina-Proteína Ligasas , Ubiquitina , Animales , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinación , Unión Proteica , Ubiquitina/metabolismo , Sitios de Unión , Mamíferos/metabolismoRESUMEN
Improving the photocatalytic performance of metal-organic frameworks (MOFs) is an important way to expand its potential applications. In this work, zero-dimensional (0D) Bi2O3 nanoparticles were anchored to the surface of tridimensional (3D) MIL101(Fe) by a facile solvothermal method to obtain a novel 0D/3D heterojunction Bi2O3/MIL101(Fe) (BOM). The morphology and optical properties of the as-prepared Bi2O3/MIL101(Fe) composite were characterized. The photocatalytic activity of the synthesized samples was evaluated by degrading chlortetracycline (CTC) under visible-light irradiation. The obtained BOM-20 composite (20 wt % Bi2O3/MIL101(Fe)) exhibits the highest photocatalytic activity with CTC degradation efficiency of 88.2% within 120 min. The degradation rate constant of BOM-20 toward CTC is 0.01348 min-1, which is 5.9 and 4.3 times higher than that of pristine Bi2O3 and MIL101(Fe), respectively. The enhanced photocatalytic activity is attributed to the formation of a Z-scheme heterojunction between Bi2O3 and MIL101(Fe), which is conducive to the rapid separation of photogenerated carriers and the enhancement of photogenerated electron and hole redox capacity. The intermediate products were analyzed by liquid chromatography-mass spectrometry (LC-MS), and a possible photocatalytic degradation path of CTC was proposed. This work provides a new perspective for the preparation of efficient MOF-based photocatalysts.
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Bromate (BrO3-) is a predominant undesired toxic disinfection by-product (DBP) during ozonation of bromide-containing waters. The reduction of BrO3- by zero valent iron (ZVI) and its effect on formation of organic halogenated DBPs during chlorination were investigated in this study. The presence of ZVI could reduce BrO3- to bromide (Br-), and Br- formed could be transformed to free bromine (HOBr/OBr-) during chlorination, further leading to organic brominated (Br-) DBPs formation. Formation of DBPs during chlorination, including trihalomethanes (THMs) and haloacetonitriles (HANs) was detected under different conditions. The results showed that when ZVI dosage increased from 0 to 1 g L-1, the formation of Br-DBPs (e.g., TBM and DBCM) was significantly improved, while the formation of Cl-DBPs (e.g., TCM, TCAN and DCAN) reduced. Higher ZVI dosage exhibited inhibitory effect on Br-DBPs formation due to the competition between ZVI and free chlorine (HOCl/OCl-). The bromine substitution factor (BSF) of THMs significantly decreased from 0.61 ± 0.06 to 0.22 ± 0.02, as the pH was raised from 5.0 to 9.0. Besides, the increase of initial BrO3- concentration significantly improved the formation of Br-DBPs and decreased the formation of Cl-DBPs, leading to an obvious rise on the BSF of THMs. As the initial concentration of HOCl increased, all THMs and HANs gradually increased. Moreover, the analysis based on the cytotoxicity index (CTI) of the determined DBPs showed that reduction of BrO3- by ZVI during chlorination had certain risks in real water sources, which should be paid attention to in the application.
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Desinfectantes , Contaminantes Químicos del Agua , Purificación del Agua , Bromatos , Bromuros , Desinfección , Halogenación , Hierro , Trihalometanos , Contaminantes Químicos del Agua/análisisRESUMEN
Vacuum ultraviolet/ultraviolet (VUV/UV) process has been applied to water treatment recently, but little is known about its efficacy and mechanism for pesticide degradation. This study investigated the degradation kinetics and mechanism of a typical organophosphorus pesticide, dimethoate (DMT) by VUV/UV, and then the economic feasibility was assessed. DMT degradation followed well the pseudo-first-order reaction kinetics at an initial concentration of ≤5.0 mg L-1. DMT was degraded by 97.8% after 10 min of VUV/UV exposure (VUV fluence = 12 mJ cm-2), whereas by only 5.2% after 10 min of UV exposure (UV fluence = 156 mJ cm-2). The apparent quantum yield of DMT degradation by VUV/UV was determined to be 0.19, and at most 50.7% of hydroxyl radicals (HOâ¢) generated from VUV photolysis of water could be utilized for DMT degradation. As the pH increased from 5.0 to 9.0, the DMT degradation rate decreased from 0.43 to 0.23 min-1. DMT degradation pathways in the VUV/UV process were proposed based on identified organic intermediates and inorganic ions. SO42- was first released due to HO⢠attack on the SP bond of DMT, which governed the DMT degradation efficiency; while the release of PO43- was pertinent to the DMT mineralization efficiency. DMT solution toxicity was significantly reduced after VUV/UV treatment. An electrical energy-per-order (EEO) value of 0.57 kWh m-3 Order-1 demonstrated the economic feasibility of the VUV/UV process for DMT removal in small-scale drinking water treatment.
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Contaminantes Químicos del Agua , Purificación del Agua , Dimetoato , Estudios de Factibilidad , Cinética , Oxidación-Reducción , Fotólisis , Rayos Ultravioleta , Vacio , Contaminantes Químicos del Agua/análisisRESUMEN
A spindle-like monoclinic-tetragonal heterojunction BiVO4 was successfully synthesized by a pressure-controllable microwave method. The as-prepared BiVO4 samples were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), UV-vis diffuse reflectance spectroscopy (DRS), photoluminescence (PL) spectroscopy, transient photocurrent responses and electrochemical impedance spectroscopy (EIS). The visible-light-driven photocatalytic activity of the BiVO4 samples was evaluated for the degradation of Rhodamine B (RhB) and tetracycline (TC). The synthesis process needs microwave irradiation for only 10 min without the addition of any auxiliary reagent, pH adjustment, and calcination. The as-prepared spindle-like monoclinic-tetragonal heterojunction BiVO4 exhibits excellent photocatalytic activity for the degradation of both RhB and TC. The photocatalytic degradation rates of RhB and TC over spindle-like BiVO4 are 1.77 and 1.64 times higher, respectively, than that measured over monoclinic BiVO4. The enhanced photocatalytic activity is mainly attributed to the fact that the existence of a heterojunction effectively promotes the separation of photo-generated carriers and extends the visible-light absorption of BiVO4.
RESUMEN
Photocatalysis is considered to be a promising technique for the degradation of organic pollutants. Herein, a 0D/1D composite photocatalyst consisting of Au nanoparticles (NPs) and CuBi2O4 microrods (Au/CBO) was designed and prepared by a simple thermal reduction-precipitation approach. It shows excellent photocatalytic performance in the degradation of tetracycline (TC). The maximum photocatalytic degradation rate constant for Au/CBO composites with 2.5 wt % Au NPs was 4.76 times as high as that of bare CBO microrods. Additionally, the 0D/1D Au/CBO composite also exhibited ideal stability. The significant improvement of the photocatalytic performance could be attributed to the improved light harvesting and increased specific surface area, enhancing photoresponse and providing more active sites. Our work shows a possible design of efficient photocatalysts for environmental remediation.
RESUMEN
The degradation of sulfamethazine (SMN) by VUV/UV photo-Fenton (VPF) process was investigated with a mini-fluidic VUV/UV photoreaction system. Compared with the conventional UV photo-Fenton process, the VPF process significantly enhanced the degradation and mineralization of SMN, because the VUV irradiation photolyzed H2O and accelerated the redox cycle of Fe3+/Fe2+ to generate more reactive oxygen species (ROS). Initial pH and concentrations of SMN, H2O2, Fe3+, inorganic anions (NO3-, HCO3-, and Cl-), and humic acid all considerably impacted SMN degradation in the VPF process. In particular, the initial SMN concentration significantly affected the absorption distributions of UV and VUV photons in the reaction solution, thus inducing a different reaction mechanism. At a lower SMN concentration (1.8µM), most of UV and VUV photons were absorbed by Fe3+ and H2O, respectively, so indirect oxidation by ROS mainly accounted for SMN degradation. However, at a higher SMN concentration (90µM), 89.2% of UV photons and 59.0% of VUV photons were absorbed by SMN, so direct photolysis also played an important role. In addition, HO and HO2 were identified as the main ROS in the VPF process. This study demonstrates that the VPF process can effectively remove organic micropollutants from water.