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Interest in the use of proteolysis-targeting chimeras (PROTACs) in cancer therapy has increased in recent years. Targeting bromodomain and extra terminal domain (BET) proteins, especially bromodomain-containing protein 4 (BRD4), has shown inhibitory effects on basal-like breast cancer (BLBC). However, the bioavailability of BRD4 PROTACs is restricted by their non-selective biodegradability and low tumor-targeting ability. We demonstrated that 6b (BRD4 PROTAC) suppresses BLBC cell growth by targeting BRD4, but not BRD2 and BRD3, for cereblon (CRBN)-mediated ubiquitination and proteasomal degradation. Compound 6b also inhibited expression of Krüppel-like factor 5 (KLF5) transcription factor, a key oncoprotein in BLBC, controlled by BRD4-mediated super-enhancers. Moreover, 6b inhibited HCC1806 tumor growth in a xenograft mouse model. The combination of 6b and KLF5 inhibitors showed additive effects on BLBC. These results suggest that BRD4-specific PROTAC can effectively inhibit BLBC by downregulating KLF5, and that 6b has potential as a novel therapeutic drug for BLBC.
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Objective: COPD patients have a high incidence of frailty and numerous complications, which seriously affect their quality of life. This study systematically evaluated and analyzed the current state of frailty incidence and risk factors in COPD patients to reduce the prevalence of frailty and enhance their quality of life. Method: The Cochrane Library, PubMed, Embase, Web of Science, CBM, CNKI, VIP, and Wanfang databases were searched for relevant studies from the inception of each database until November 2022. A thorough literature screening, quality evaluation, and data extraction was conducted. Meta-analysis was performed using RevMan5.3Meta. Twelve articles were selected as most relevant to this review; 10 were in Chinese, and 2 were in English. Results: The results showed that the incidence of asthenia in COPD patients was 26% (OR 0.26, 95% CI 0.17~0.34). Discussion: The main risk factors for frailty in COPD patients were age (OR 1.32, 95% CI 1.30~1.34), GOLD pulmonary function class (OR 3.18, 95% CI 2.14~4.71), mMRC score (OR 3.90, 95% CI 1.53~9.92), comorbidity (OR 2.17, 95% CI 1.48~3.18), polypharmacy (OR 6.74, 95% CI 3.23~14.08), malnutrition (OR 3.32, 95% CI 1.77~6.24), depression (OR 1.37, 95% CI 1.07~1.76) and ≥2 admissions within 1 year (OR 4.84, 95% CI 2.45~9.57). Conclusion: The study presented comprehensive evidence through meta-analysis and proposed that the prevalence of frailty in COPD patients is 26%. Risk factors were identified, including age, pulmonary function class according to GOLD criteria, mMRC score, comorbidity polypharmacy malnutrition, depression, or 2 or more hospital admissions within a year. It is recommended that clinical medical staff identify these risk factors at an early stage.
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Natural products, while valuable for drug discovery, encounter limitations like uncertainty in targets and toxicity. As an important active ingredient in traditional Chinese medicine, celastrol exhibits a wide range of biological activities, yet its mechanism remains unclear. In this study, they introduced an innovative "Degradation-based protein profiling (DBPP)" strategy, which combined PROteolysis TArgeting Chimeras (PROTAC) technology with quantitative proteomics and Immunoprecipitation-Mass Spectrometry (IP-MS) techniques, to identify multiple targets of natural products using a toolbox of degraders. Taking celastrol as an example, they successfully identified its known targets, including inhibitor of nuclear factor kappa B kinase subunit beta (IKKß), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PI3Kα), and cellular inhibitor of PP2A (CIP2A), as well as potential new targets such as checkpoint kinase 1 (CHK1), O-GlcNAcase (OGA), and DNA excision repair protein ERCC-6-like (ERCC6L). Furthermore, the first glycosidase degrader is developed in this work. Finally, by employing a mixed PROTAC toolbox in quantitative proteomics, they also achieved multi-target identification of celastrol, significantly reducing costs while improving efficiency. Taken together, they believe that the DBPP strategy can complement existing target identification strategies, thereby facilitating the rapid advancement of the pharmaceutical field.
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Triterpenos Pentacíclicos , Proteómica , Triterpenos , Proteómica/métodos , Humanos , Triterpenos/farmacología , Triterpenos/metabolismo , Proteolisis/efectos de los fármacos , Espectrometría de Masas/métodos , Inmunoprecipitación/métodosRESUMEN
Undruggable targets typically refer to a class of therapeutic targets that are difficult to target through conventional methods or have not yet been targeted, but are of great clinical significance. According to statistics, over 80% of disease-related pathogenic proteins cannot be targeted by current conventional treatment methods. In recent years, with the advancement of basic research and new technologies, the development of various new technologies and mechanisms has brought new perspectives to overcome challenging drug targets. Among them, targeted protein degradation technology is a breakthrough drug development strategy for challenging drug targets. This technology can specifically identify target proteins and directly degrade pathogenic target proteins by utilizing the inherent protein degradation pathways within cells. This new form of drug development includes various types such as proteolysis targeting chimera (PROTAC), molecular glue, lysosome-targeting Chimaera (LYTAC), autophagosome-tethering compound (ATTEC), autophagy-targeting chimera (AUTAC), autophagy-targeting chimera (AUTOTAC), degrader-antibody conjugate (DAC). This article systematically summarizes the application of targeted protein degradation technology in the development of degraders for challenging drug targets. Finally, the article looks forward to the future development direction and application prospects of targeted protein degradation technology.
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Autofagia , Proteolisis , Proteolisis/efectos de los fármacos , Humanos , Autofagia/efectos de los fármacos , Proteínas/metabolismo , Lisosomas/metabolismo , Desarrollo de Medicamentos/métodos , Terapia Molecular Dirigida/métodos , AnimalesRESUMEN
The theoretically infinite compositional space of high-entropy alloys (HEAs) and their novel properties and applications have attracted significant attention from a broader research community. The successful synthesis of high-quality single-phase HEA nanoparticles represents a crucial step in fully unlocking the potential of this new class of materials to drive innovations. This review analyzes the various methods reported in the literature to identify their commonalities and dissimilarities, which allows categorizing these methods into five general strategies. Physical minimization of HEA metals into HEA nanoparticles through cryo-milling represents the typical top-down strategy. The counter bottom-up strategy requires the simultaneous generation and precipitation of metal atoms of different elements on growing nanoparticles. Depending on the metal atom generation process, there are four synthesis strategies: vaporization of metals, burst reduction of metal precursors, thermal shock-induced reduction of metal precursors, and solvothermal reduction of metal precursors. Comparisons among the methods within each strategy, along with discussions, provide insights and guidance for achieving the robust synthesis of HEA nanoparticles.
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Heavy metal complexes receive less attention, but they are more difficult to remove than the free heavy metals. Moreover, the high-salinity wastewaters from various industries hinder the removal of heavy metal complexes. Removal of the metal complexes is a top priority but a challenging task. Herein, a new strategy for removing Cu-EDTA from high-salinity wastewater with sulfide-modified nanozerovalent iron (S-NZVI) was proposed. The S-NZVI exhibited a considerable adsorption capacity for Cu-EDTA (â¼83 mg Cu/g) at a high salt concentration (25 g/L NaCl). Similarly, the S-NZVI maintained excellent adsorption performance (â¼83 mg Cu/g) in the presence of CaCl2, MgCl2, Na2SO4, and NaNO3 (25 g/L). The S-NZVI showed extremely high efficiency for Cu-EDTA removal; 50 mg/L of Cu-EDTA was almost completely removed in 1 min, and the kobs was approximately 1.5 g/(mg min). The S-NZVI showed an extensive pH working range, and within the pH range of 2-9, the Cu-EDTA was removed completely within 5 min. The excellent removal performance of the S-NZVI was due to the high reactivity and high affinity of NZVI for Cu, as well as the special substitution of Fe2+ and the interfacial reactions between S-NZVI and the copper complexes. Compared with other studies of Cu complex removal, removal with S-NZVI was a simpler process with higher efficiency. In brief, S-NZVI efficiently removed Cu complexes from harsh water environments and was reused many times. The process was simple and efficient and has broad application prospects.
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Complejos de Coordinación , Metales Pesados , Contaminantes Químicos del Agua , Hierro/química , Aguas Residuales , Cobre/análisis , Salinidad , Ácido Edético , Descontaminación , Contaminantes Químicos del Agua/análisis , Sulfuros , AdsorciónRESUMEN
Candida albicans is an important opportunistic pathogenic fungus that frequently causes serious systemic infection in humans. Due to the vital roles of biofilm formation and the yeast-to-hypha transition in the infection process, we have selected a series of diaryl chalcogenides and tested their efficacy against C. albicans SC5314 pathogenicity by the inhibition of biofilm formation and the yeast-to-hypha transition. The compounds 5-sulfenylindole and 5-selenylindole were found to have excellent abilities to inhibit both biofilm formation and hyphal formation in C. albicans SC5314. Intriguingly, the two leading compounds also markedly attenuated C. albicans SC5314 virulence in human cell lines and mouse infection models at micromolar levels. Furthermore, our results showed that the presence of the compounds at 100 µM resulted in a marked decrease in the expression of genes involved in the cAMP-PKA and MAPK pathways in C. albicans SC5314. Intriguingly, the compounds 5-sulfenylindole and 5-selenylindole not only attenuated the cytotoxicity of Candida species strains but also showed excellent synergistic effects with antifungal agents against the clinical drug-resistant C. albicans strain HCH12. The compound 5-sulfenylindole showed an obvious advantage over fluconazole as it could also restore the composition and richness of the intestinal microbiota in mice infected by C. albicans. Together, these results suggest that diaryl chalcogenides can potentially be designed as novel clinical therapeutic agents against C. albicans infection. The diaryl chalcogenides of 5-sulfenylindole and 5-selenylindole discovered in this study can provide new direction for developing antifungal agents against C. albicans infection.
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Candida albicans , Candidiasis , Ratones , Humanos , Animales , Candida albicans/genética , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Virulencia , Candidiasis/tratamiento farmacológico , Candidiasis/microbiología , Fluconazol/farmacología , Hifa , BiopelículasRESUMEN
A facile and sensitive glucose sandwich assay using surface-enhanced Raman scattering (SERS) has been developed. Glucose was captured by 3-aminopheyonyl boronic acid (APBA) modified Ag nanoparticles decorated onto a polyamide surface. Then, Ag nanoparticles modified with 3-amino-6-ethynylpicolinonitrile (AEPO) and APBA were used as SERS tags. APBA forms specific cis-diol compounds with glucose molecules avoiding interference by other saccharides and biomolecules in urine enabling its selective detection. As the actual Raman reporter, AEPO exhibited a distinctive SERS peak in the Raman silent region, thus increasing the sensitivity of the glucose detection to 10-11 M. Additionally, the developed SERS assay was reusable, and its applicability in artificial urine samples demonstrated future clinical utility confirming the potential of this innovative technology as a diagnostic tool for glucose sensing.
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Glucosa , Espectrometría Raman , Oro/química , Nanopartículas del Metal/química , Plata/química , Espectrometría Raman/métodosRESUMEN
Intraoperatively acquired pressure injuries (IAPIs) occur frequently among patients who undergo surgical procedures that last longer than 3 h. Several studies indicated that heat shock proteins (HSPs) play an important role in the protection of stress-induced damages in skin tissues. Hence, the aim of this study was to investigate the potential preventive effect of thermal preconditioning (TPC) on IAPIs in surgical patients and rats and to identify the differentially expressed HSP genes in response to the above treatment. TPC was performed on one group of hairless rats before the model of pressure injuries was established. Subsequently, the size of skin lesions was measured and the expression levels of mRNA and protein of HSPs of the pressured skin were detected by real-time polymerase chain reaction (RT-PCR), western blot, and immunohistochemical staining. For human studies, 118 surgical patients were randomly divided into the TPC group (n = 59) and the control group (n = 59), respectively. The temperature and pressure of sacral skin, as well as the incidence of pressure injury (PI) were detected and compared. In animal studies, TPC significantly reduced both the size and incidence of PI in rats on the second, third and fourth days post treatment. In addition, the expression levels of both mRNA and protein of HSP27 were increased in the TPC group, compared with the control group. Immunohistochemical staining showed that HSP27 was distributed in various types of dermal cells and increased in basal cells. In human studies, a significant reduction (75%) of IAPIs was observed among the patients in the TPC group. TPC can reduce the incidence of PI in rats and humans, and the upregulation of HSP27 may play an important role in this biological progress. Further studies are warranted to explore the molecular mechanism of the preventive effect in PI mediated by HSP27.
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Úlcera por Presión , Ratas , Humanos , Animales , Úlcera por Presión/prevención & control , Proteínas de Choque Térmico HSP27/genética , Proteínas de Choque Térmico HSP27/metabolismo , Incidencia , ARN Mensajero/genética , Proteínas HSP70 de Choque Térmico/genéticaRESUMEN
The recovery of volatile fatty acids (VFAs) through anaerobic fermentation (AF) is usually restricted by the poor biodegradability of waste activated sludge (WAS). This study proposed a novel strategy, i.e. peroxymonosulfate (PMS) activated by Fe-loaded sodium alginate hydrogel beads (Fe-SA), to enhance AF performance. Experimental results demonstrated that the as-synthesized Fe-SA and PMS co-pretreatment synergistically enhanced WAS solubilization and VFAs production. The maximal VFAs yield of 2013 mg COD/L was achieved at the Fe-SA dosage of 4.0 mM/g TSS, which was 93.7% higher than that with sole PMS addition and 8.82 times higher than that of the control. Mechanistic studies elucidated that the generation of reactive radicals such as SO4â¢- and â¢OH from PMS was greatly induced by Fe-SA, which contributed to WAS disintegration and degradation of refractory compounds. Additionally, analysis of the key enzyme activities indicated that the Fe-SA could strengthen biological hydrolysis and acidogenesis of sludge during AF. Microbial analysis illustrated that Fe-SA evidently improved the abundances of fermentative microorganisms as well as functional gene expression via creating a favorable environment for microbial growth. This study demonstrated the applicable potential of Fe-SA hydrogel beads activating PMS for VFAs production and provides an important reference for developing advanced oxidation processes-based application in AF.
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Alginatos , Aguas del Alcantarillado , Fermentación , Anaerobiosis , Hidrogeles , Concentración de Iones de Hidrógeno , Ácidos Grasos VolátilesRESUMEN
A crucial issue in analytical science and physiology is the detection of histamine with high sensitivity, specificity and credibility, which served as an important neurotransmitter in biofluids. Despite the high sensitivity of surface-enhanced Raman spectroscopy (SERS) at the level of single molecule, there are still challenges in providing high sensitivity for histamine with a small cross section. For the selective detection of histamine using SERS, a highly sensitive sandwich structure substrate combining Fe3O4 and an Ag-based SERS nanotag was developed. The Fe3O4@SiO2-COOH served as a capture component for enriching histamine. Upon functionalized Ag nanoparticles with glycine (Gly) and (3-Aminopheyonyl) boronic acid (APBA), they were then used to connect with histamine and serve as a SERS nanotag, respectively. A linear relationship between the Raman intensity and the histamine concentration was observed over the range 10-4-10-8 M with a limit of detection of 7.24 × 10-9 M. This methodology also exhibited good selectivity in the presence of other neurotransmitters. With our new approach, histamine can be detected sensitively and reliably in fish samples, which indicates the potential prospect of an effective method for analyzing histamine in complex specimens.
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Nanopartículas del Metal , Animales , Nanopartículas del Metal/química , Histamina , Dióxido de Silicio/química , Oro/química , Plata/química , Espectrometría Raman/métodosRESUMEN
Candida albicans is an important human fungal pathogen. Our previous study disclosed that aryloxy-phenylpiperazine skeleton was a promising molecule to suppress C. albicans virulence by inhibiting hypha formation and biofilm formation. In order to deeply understand the efficacy and mechanism of action of phenylpiperazine compounds, and obtain new derivatives with excellent activity against C. albicans, hence, we synthesized three series of (1-heteroaryloxy-2-hydroxypropyl)-phenylpiperazines and evaluated their inhibitory activity against C. albicans both in vitro and in vivo in this study. Compared with previously reported aryloxy-phenylpiperazines, part of these heteroaryloxy derivatives improved their activities by strongly suppressing hypha formation and biofilm formation in C. albicans SC5314. Especially, (9H-carbazol-4-yl)oxy derivatives 25, 26, 27 and 28 exhibited strong activity in reducing C. albicans virulence in both human cell lines in vitro and mouse infection models in vivo. The compound 27 attenuated the virulence of various clinical C. albicans strains, including clinical drug-resistant C. albicans strains. Moreover, additive effects of the compound 27 with antifungal drugs against drug-resistant C. albicans strains were also discussed. Furthermore, the compound 27 significantly improved the composition and richness of the faecal microbiota in mice infected by C. albicans. These findings indicate that these piperazine compounds have great potential to be developed as new therapeutic drugs against C. albicans infection.
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Candida albicans , Candidiasis , Humanos , Animales , Ratones , Candidiasis/tratamiento farmacológico , Candidiasis/microbiología , Antifúngicos/farmacología , Piperazinas/farmacología , BiopelículasRESUMEN
Upon contacting with water, cold plasma should produce numerous ozone molecules and free electrons at room temperature. In this study, a cold plasma generator was used to break the walls of residual activated sludge obtained from domestic sewage. The impact was mainly influenced by the ozone generated. With 800â W power, sludge wastewater pH of 12.0, and under continuous treatment for 10â h, the system's reduction efficiency for the dry sludge was ≈90%. Furthermore, the organic matter content (especially protein) of the upper layer of the sludge solution increased a lot after the sludge digestion. This observation proved the reduction of sludge from both sides. Moreover, when the cold plasma technique was compared with thermal acid hydrolysis, thermal alkali hydrolysis, and ultrasonication for extracting protein from activated sludge, cold plasma wall-breaking sludge exhibited the highest efficiency, reaching 38.2% under ambient temperature. After the analysis, the toxic metal content in the extracted protein was near zero, which is a level other protein extraction methods via sludge breaking have not achieved to date, we attribute this efficiency to free electrons the cold plasma produce. These species promote the transformation of metal ions into atomic metals, thereby facilitating their removal.
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Ozono , Gases em Plasma , Aguas del Alcantarillado/química , Gases em Plasma/análisis , Eliminación de Residuos Líquidos/métodos , Aguas Residuales , Metales , ProteínasRESUMEN
In this work, polyacrylonitrile/aminated polymeric nanosphere (PAN/APN) nanofibers were prepared by electrospinning of monodispersed aminated polymeric nanospheres (APNs) for removal of Cr(VI) from aqueous solution. Characterization results showed that obtained PAN/APNs possessed nitrogen functionalization. Furthermore, the adsorption application results indicated that PAN/APN nanofibers exhibited a high adsorption capacity of 556 mg/g at 298 K for Cr(VI) removal. The kinetic data showed that the adsorption process fits the pseudo-second order. A thermodynamic study revealed that the adsorption of Cr(VI) was spontaneous and endothermic. The coexisting ions Na+, Ca2+, K+, Cl-, NO3- and PO43- had little influence on Cr(VI) adsorption, while SO42- in solution dramatically decreased the removal performance. In the investigation of the removal mechanism, relative results indicated that the adsorption behavior possibly involved electrostatic adsorption, redox reaction and chelation. PAN/APN nanofibers can detoxify Cr(VI) to Cr(III) and subsequently chelate Cr(III) on its surface. The unique structure and nitrogen functionalization of PAN/APN nanofibers make them novel and prospective candidates in heavy metal removal.
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Metales Pesados , Nanofibras , Nanosferas , Contaminantes Químicos del Agua , Nanofibras/química , Contaminantes Químicos del Agua/química , Cromo/química , Adsorción , Cinética , Polímeros , Iones , NitrógenoRESUMEN
Developing new catalysts for efficient degradation of micropollutants in water is of significant importance in advanced oxidation processes (AOPs). Herein, TiO2/C coated Co3O4 nanocages (Co3O4@TiO2/C) were synthesized and their performance on micropollutants degradation was evaluated. Specifically, cobalt-based Zeolitic imidazolate framework (ZIF-67) coated by a thin layer of titanium species and polydopamine (PDA) was used as a precursor for the preparation of Co3O4@TiO2/C by two-step calcination. The catalytic performance of peroxymonosulfate (PMS) activation towards the degradation of organic pollutants was investigated by using atrazine (ATZ) and Bisphenol A (BPA) as typical micropollutants. The efficiency and the effect of TiO2/C shell on the as-synthesized catalyst were analyzed by comparing Co3O4 derived from ZIF-67 and Co3O4/C derived from ZIF-67/PDA. ATZ degradation results showed that the Co3O4@TiO2/C catalyst was the most efficient for catalytic oxidation when 99.5% of ATZ was removed within 4 min, which is 57.5% and 74.6% faster than that of Co3O4@C and Co3O4, respectively. The enhanced performance of Co3O4@TiO2/C is attributed to their unique nanocages structure and improved specific surface area. The catalysis mechanisms and ATZ degradation pathways were presented based on the results of electron paramagnetic resonance (EPR), XPS, and LC-MS analysis. Our results might have added to the design of heterogeneous catalysts of large surface area for efficient PMS activation in AOPs.
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Atrazina , Contaminantes Ambientales , Cobalto/química , Óxidos , Peróxidos/química , Titanio , AguaRESUMEN
Burkholderia cenocepacia is a human opportunistic pathogen that mostly employs two types of quorum-sensing (QS) systems to regulate its various biological functions and pathogenicity: the cis-2-dodecenoic acid (BDSF) system and the N-acyl homoserine lactone (AHL) system. In this study, we reported that oridonin, which was screened from a collection of natural products, disrupted important B. cenocepacia phenotypes, including motility, biofilm formation, protease production, and virulence. Genetic and biochemical analyses showed that oridonin inhibited the production of BDSF and AHL signals by decreasing the expression of their synthase-encoding genes. Furthermore, we revealed that oridonin directly binds to the regulator RqpR of the two-component system RqpSR that dominates the above-mentioned QS systems to inhibit the expression of the BDSF and AHL signal synthase-encoding genes. Oridonin also binds to the transcriptional regulator CepR of the cep AHL system to inhibit its binding to the promoter of bclACB. These findings suggest that oridonin could potentially be developed as a new QS inhibitor against pathogenic B. cenocepacia. IMPORTANCE Burkholderia cenocepacia is an important human opportunistic pathogen that can cause life-threatening infections in susceptible individuals. It employs quorum-sensing (QS) systems to regulate biological functions and virulence. In this study, we have identified a lead compound, oridonin, that is capable of interfering with B. cenocepacia QS signaling and physiology. We demonstrate that oridonin suppressed cis-2-dodecenoic acid (BDSF) and N-acyl homoserine lactone (AHL) signal production and attenuated virulence in B. cenocepacia. Oridonin also impaired QS-regulated phenotypes in various Burkholderia species. These results suggest that oridonin could interfere with QS signaling in many Burkholderia species and might be developed as a new antibacterial agent.
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Burkholderia cenocepacia , Acil-Butirolactonas/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Burkholderia cenocepacia/genética , Burkholderia cenocepacia/metabolismo , Diterpenos de Tipo Kaurano , Regulación Bacteriana de la Expresión Génica , Humanos , Percepción de Quorum , Virulencia/genéticaRESUMEN
The serious environmental risks caused by Pb(II) and Sb(V) co-contamination increase the need for their efficient and simultaneous removal. In this study, the remediation feasibility by Fe-doped phosphogypsum (FPG) was elucidated for single systems with Pb or Sb pollutant and coexisting systems with both from water. As for single systems, Fe doping effectively enhanced the Pb(II) removal performance by phosphogypsum (PG) at low Pb(II) concentrations of below 100 mg/L via the combination of precipitation and complexation. The optimal removal rate of Sb(V) by FPG increased by 2.08-3.31 times as compared to that of by PG (10-120 mg/L), mainly due to the strong affinity of iron hydroxyl (≡Fe-O-H) towards Sb(V). Compared with the single systems, the coexistence greatly enhanced the Pb(II) and Sb(V) removal performance by FPG, and the interaction behavior between Pb(II) and Sb(V) on the FPG was concentration dependent. Briefly, the sorption of FPG controlled the elimination of low coexisting concentrations of Pb(II) and Sb(V), whereas the co-precipitation process between Pb(II) and Sb(V) predominated with high ions concentration. The significant synergistic effects were found during the removal of Pb(II) and Sb(V) on FPG in the coexisting system, which mainly attributed to precipitation, bridging complexation and electrostatic attraction. Considering the advantages such as facile preparation, low cost and high removal capacity, FPG is a promising material to uptake Pb(II) and/or Sb(V) from contaminated water.
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Hierro , Contaminantes Químicos del Agua , Antimonio/análisis , Agua , Plomo , Adsorción , Contaminantes Químicos del Agua/análisisRESUMEN
PROteolysis TArgeting Chimeras (PROTACs) technology is a new protein-degradation strategy that has emerged in recent years. It uses bifunctional small molecules to induce the ubiquitination and degradation of target proteins through the ubiquitin-proteasome system. PROTACs can not only be used as potential clinical treatments for diseases such as cancer, immune disorders, viral infections, and neurodegenerative diseases, but also provide unique chemical knockdown tools for biological research in a catalytic, reversible, and rapid manner. In 2019, our group published a review article "PROTACs: great opportunities for academia and industry" in the journal, summarizing the representative compounds of PROTACs reported before the end of 2019. In the past 2 years, the entire field of protein degradation has experienced rapid development, including not only a large increase in the number of research papers on protein-degradation technology but also a rapid increase in the number of small-molecule degraders that have entered the clinical and will enter the clinical stage. In addition to PROTAC and molecular glue technology, other new degradation technologies are also developing rapidly. In this article, we mainly summarize and review the representative PROTACs of related targets published in 2020-2021 to present to researchers the exciting developments in the field of protein degradation. The problems that need to be solved in this field will also be briefly introduced.
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Ubiquitina-Proteína Ligasas , Complejo de la Endopetidasa Proteasomal/metabolismo , Proteolisis , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
Single oxygen-based advanced oxidation processes (1O2-AOPs) exhibit great prospects in selective degradation of organic pollutants. However, efficient production of 1O2 via tailored design of catalysts to achieve selective oxidation of contaminants remains challenging. Herein, we develop a simple strategy to regulate the components and coordination of Co-N-C catalysts at the atomic level by adjusting the Zn/Co ratio of bimetallic zeolitic imidazolate frameworks (ZnxCo1-ZIFs). Zn4Co1-C demonstrates 98% selective removal of phenol in the mixed phenol/benzoic acid (phenol/BA) solutions. Density functional theory calculations and experiments reveal that more active CoN4 sites are generated in Zn4Co1-C, which are beneficial to peroxymonosulfate activation to generate 1O2. Furthermore, the correlation between the origin of selectivity and well-defined catalysts is systematically investigated by the electron paramagnetic resonance test and quenching experiments. This work may provide novel insights into selective removal of target pollutants in a complicated water matrix.