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Ammonia monohydrate (NH3·H2O) is an important chemical widely used in industrial, agricultural, and pharmaceutical fields. Reject water is used as the raw material in self-built bipolar membrane electrodialysis (BMED) to produce NH3·H2O. The effects of electrode materials, membrane stack structure, and operating conditions (current density, initial concentrations of the reject water, and initial volume ratio) on the BMED process were investigated, and the economic costs were analyzed. The results showed that compared with graphite electrodes, ruthenium-iridium-titanium electrodes as electrode plates for BMED could increase current efficiency (25%) and reduce energy consumption (26%). Compared with two-compartment BMED, three-compartment BMED had a higher ammonia nitrogen conversion rate (86.6%) and lower energy consumption (3.5â kW· h/kg). Higher current density (15â mA/cm2) could achieve better current efficiency (79%). The BMED performances were improved when the initial NH4+ concentrations of the reject water increased from 500â mg NH4+/L to 1000â mg NH4+/L, but the performance decreased as the concentration increased from 1000â mg NH4+/L to 1500â mg NH4+/L. High initial volume ratio of the salt compartment and product compartment was beneficial for reducing energy consumption. Under the optimal operating conditions, only 0.13 $/kg reject water was needed to eliminate the environmental impact of reject water accumulation. This work indicates that BMED can not only achieve desalination of reject water, but also generate products that alleviate the operational pressure of factories.
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The integration of high-rate activated sludge (HRAS), an effective carbon redirection technology, with partial nitritation/anammox (PN/A) is a novel AB treatment process for municipal wastewater. In this study, an airlift HRAS reactor was operated in the continuous inflow mode for 200 d at a wastewater treatment plant. The balance between potential PN/A system stability and peak HRAS performance under decreasing hydraulic retention time (HRT) was optimized. Energy consumption and recovery and CO2 emissions were calculated. The results showed that the optimal HRT suitable with the PN/A process was 3 h, achieving 2-3 g/L mixed liquor volatile suspended solid, 67.8 % chemical oxygen demand (COD) recovery, 81 % total COD removal efficiency, 2.27 ± 1.03 g COD/L/d organic loading rate, 62 % aeration reduction, and 0.24 kWh/m3 power recovery potential. Such findings hold practical value and contribute to the development of the optimal AB process capable of achieving energy autonomy and carbon neutrality.
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Reatores Biológicos , Esgotos , Purificação da Água , Purificação da Água/métodos , Águas Residuárias/química , Análise da Demanda Biológica de Oxigênio , Eliminação de Resíduos Líquidos/métodos , Fatores de Tempo , Nitrogênio , Dióxido de Carbono , Oxirredução , CidadesRESUMO
BACKGROUND: Bleomycin, a potent antitumor agent, is limited in clinical use due to the potential for fatal pulmonary toxicity. The accelerated DNA damage and senescence in alveolar epithelial cells (AECs) is considered a key factor in the development of lung pathology. Understanding the mechanisms for bleomycin-induced lung injury is crucial for mitigating its adverse effects. METHODS: Human lung epithelial (A549) cells were exposed to bleomycin and subsequently assessed for cellular senescence, DNA damage, and double-strand break (DSB) repair. The impact of Rad51 overexpression on DSB repair and senescence in AECs was evaluated in vitro. Additionally, bleomycin was intratracheally administered in C57BL/6 mice to establish a pulmonary fibrosis model. RESULTS: Bleomycin exposure induced dose- and time-dependent accumulation of senescence hallmarks and DNA lesions in AECs. These effects are probably due to the inhibition of Rad51 expression, consequently suppressing homologous recombination (HR) repair. Mechanistic studies revealed that bleomycin-mediated transcriptional inhibition of Rad51 might primarily result from E2F1 depletion. Furthermore, the genetic supplement of Rad51 substantially mitigated bleomycin-mediated effects on DSB repair and senescence in AECs. Notably, decreased Rad51 expression was also observed in the bleomycin-induced mouse pulmonary fibrosis model. CONCLUSIONS: Our works suggest that the inhibition of Rad51 plays a pivotal role in bleomycin-induced AECs senescence and lung injury, offering potential strategies to alleviate the pulmonary toxicity of bleomycin.
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Bleomicina , Senescência Celular , Reparo do DNA , Rad51 Recombinase , Bleomicina/efeitos adversos , Rad51 Recombinase/metabolismo , Rad51 Recombinase/genética , Animais , Senescência Celular/efeitos dos fármacos , Senescência Celular/genética , Humanos , Camundongos , Reparo do DNA/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/genética , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Células A549 , Dano ao DNA/efeitos dos fármacos , Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Fator de Transcrição E2F1/metabolismo , Fator de Transcrição E2F1/genética , Células Epiteliais Alveolares/metabolismo , Células Epiteliais Alveolares/efeitos dos fármacosRESUMO
Hemiacetal compounds are valuable building blocks in synthetic chemistry, but their enzymatic synthesis is limited and often hindered by the instability of hemiacetals in aqueous environments. Here, we show that this challenge can be addressed through reaction engineering by using immobilized peroxygenase from Agrocybe aegerita (AaeUPO) under neat reaction conditions, which allows for the selective C-H bond oxyfunctionalization of environmentally significant cyclic ethers to cyclic hemiacetals. A wide range of chiral cyclic hemiacetal products are prepared in >99% enantiomeric excess and 95170 turnover numbers of AaeUPO. Furthermore, by changing the reaction medium from pure organic solvent to alkaline aqueous conditions, cyclic hemiacetals are in situ transformed into lactones. Lactams are obtained under the applied conditions, albeit with low enzyme activity. These findings showcase the synthetic potential of AaeUPO and offer a practical enzymatic approach to produce chiral cyclic hemiacetals through C-H oxyfunctionalization under mild conditions.
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The start-up and stable operation of partial nitritation-anammox (PN/A) treatment of mature landfill leachate (MLL) still face challenges. This study developed an innovative staged pilot-scale PN/A system to enhance nitrogen removal from MLL. The staged process included a PN unit, an anammox upflow enhanced internal circulation biofilm (UEICB) reactor, and a post-biofilm unit. Rapid start-up of the continuous flow PN process (full-concentration MLL) was achieved within 35 days by controlling dissolved oxygen and leveraging free ammonia and free nitrous acid to selectively suppress nitrite-oxidizing bacteria (NOB). The UEICB was equipped with an annular flow agitator combined with the enhanced internal circulation device of the guide tube, which achieved an efficient enrichment of Candidatus Kuenenia in the biofilm (relative abundance of 33.4â¯%). The nitrogen removal alliance formed by the salt-tolerant anammox bacterium (Candidatus Kuenenia) and denitrifying bacteria (unclassified SBR1031 and Denitratisoma) achieved efficient nitrogen removal of UEICB (total nitrogen removal percentage: 90.8â¯%) and at the same time effective treatment of the refractory organic matter (ROM). The dual membrane process of UEICB fixed biofilm combined with post-biofilm is effective in sludge retention, and can stably control the effluent suspended solids (SS) at a level of less than 5â¯mg/L. The post-biofilm unit ensured that effluent total nitrogen (TN) remained below the 40â¯mg/L discharge standard (98.5â¯% removal efficiency). Compared with conventional nitrification-denitrification systems, the staged PN/A process substantially reduced oxygen consumption, sludge production, CO2 emissions and carbon consumption by 22.8â¯%, 67.1â¯%, 87.1â¯% and 87.1â¯%, respectively. The 195-day stable operation marks the effective implementation of the innovative pilot-scale PN/A process in treating actual MLL. This study provides insights into strategies for rapid start-up, robust NOB suppression, and anammox biomass retention to advance the application of PN/A in high-ammonia low-carbon wastewater.
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Desnitrificação , Poluentes Químicos da Água , Amônia , Nitritos , Nitrogênio , Esgotos , Biomassa , Oxidação Anaeróbia da Amônia , Reatores Biológicos/microbiologia , Oxirredução , Nitrificação , Bactérias , CarbonoRESUMO
The adsorptive separation of propylene and propane offers an energy-efficient alternative to the conventional cryogenic distillation technology. However, developing porous adsorbents with both high equilibrium and kinetic selectivity remains extremely challenging due to the similar size and physical properties of these gases. Herein, this work reports a ligand racemization strategy to construct quasi-discrete pores in MOFs for a synergistically enhanced thermodynamic and kinetic separation performance. The use of enantiopure l-malic acid versus racemic dl-malic acid as ligands afforded isoreticular Ni-based MOFs with contrasting one-dimensional channels (l-mal-MOF) and quasi-discrete cavities connected by small windows (dl-mal-MOF). The periodic pore constrictions in dl-mal-MOF significantly increased the differentiation in diffusion rates and binding energies between propylene and propane. dl-mal-MOF exhibited an exceptional propylene uptake of 1.82 mmol/g at 0.05 bar and 298 K along with an ultrahigh equilibrium-kinetic combined selectivity of 62.6. DFT calculations and MD simulations provided insights into the synergistic mechanism of preferential propylene adsorption and diffusion. Breakthrough column experiments demonstrated the excellent separation and high-purity recovery of propylene over propane on dl-mal-MOF. The robust stability and facile regeneration highlight its potential for propylene purification applications.
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Objective: This study aimed to assess the efficacy of individual-donation nucleic acid testing (ID-NAT) in detecting occult hepatitis B virus infection (OBI) among anti-HBc positive blood donors, compared to minipool nucleic acid testing (MP-NAT). Methods: The present study analyzed data from the Shandong Blood Center in China during the period from January 2018 to June 2022, where HBsAg-negative blood donors were screened using the 6-sample minipool nucleic acid testing (6-sample MP NAT) method. NAT-positive samples underwent subsequent anti-HBc and anti-HBs testing. Approximately 5000 samples that passed the nucleic acid mixing test were randomly selected for anti-HBc testing, and over 100 anti-HBc positive samples underwent individual donor nucleic acid testing (ID-NAT). Any HBV DNA positive samples detected by ID-NAT were subsequently confirmed using alternative nucleic acid testing methods. Results: Among 220,445 HBsAg-negative blood donors, the positivity rate of HBV DNA detection using the 6-sample minipool nucleic acid testing (MP NAT) method was found to be 0.031% (69/220,445). Of the 67 HBV DNA positive samples, 55 (82.09%) and 25 (37.31%) were found to be positive for anti-HBc and anti-HBs, respectively, using the supplementary chemiluminescent microparticle immunoassay (CMIA). Among the 4797 HBsAg-negative/MP NAT-negative samples, 909 (18.95%) tested positive for anti-HBc. Further NAT testing was performed on 164 arbitrarily selected anti-HBc-positive/MP HBV DNA-negative samples, revealing a HBV DNA positivity rate of 1.22% (2/164). Conclusion: Using individual donation nucleic acid testing can significantly increase the detection rate of occult hepatitis B virus infection in anti-HBc-positive blood donors, resulting in a detection rate of 0.22% (1.22 × 0.1895). This rate is 8.10 times higher than the detection rate achieved by mixed testing methods (0.031%) [calculated as (0.22 + 0.031)/0.031]. Therefore, it is recommended to perform single HBV DNA testing on anti-HBc-positive blood donors, discard plasma with weakly positive or negative anti-HBs but positive anti-HBc, or avoid transfusing anti-HBc-positive plasma to recipients with weakly positive or negative anti-HBs to prevent HBV infection.
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This study evaluated the functional activity and microbial structure of a pre-denitrification and single-stage partial nitritation/anammox process (DB-SNAP) coupled system for effectively treating swine manure digestate (SMD). At influent ammonium concentrations of (1000 to 1500) mg/L, the pre-denitrification reactor increased the nitrogen removal efficiency (NRE) by 5%, resulting in an average NRE of 96%. The DB-SNAP and nitrogen-limited strategy facilitated the rapid adoption of anammox bacteria (AnAOB) in the SMD, maintaining a high specific rate of 0.3gN/gVSS/d. A high secretion of tightly bound extracellular polymeric substances (76 mg/gVSS to 102 mg/gVSS) promoted micro-granule aggregation and stability. Moreover, Ca. Kuenenia, an AnAOB genus, was highly enriched from 21% to (27 to 30) %, whereas Nitrospira, a nitrite-oxidizing bacteria, was significantly suppressed to (0 to 0.05) %. These findings will provide valuable guidance in implementing the anammox process in swine wastewater treatment.
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Compostos de Amônio , Desnitrificação , Animais , Suínos , Esterco , Nitrogênio , Oxidação Anaeróbia da Amônia , Reatores Biológicos/microbiologia , Oxirredução , Bactérias , EsgotosRESUMO
Strictosidine synthase (STR) catalyzes the Pictet-Spengler (PS) reaction of tryptamine and secologanin to produce strictosidine. Recent studies demonstrated that the enzyme can also catalyze the reaction of non-natural substrates to form new alkaloid skeletons. For example, the PS condensation of 1H-indole-4-ethanamine with secologanin could be promoted by the STR from Rauvolfia serpentina (RsSTR) to generate a rare class of skeletons with a seven-membered ring, namely azepino-[3,4,5-cd]-indoles, which are precursors for the synthesis of new compounds displaying antimalarial activity. In the present study, the detailed reaction mechanism of RsSTR-catalyzed formation of the rare seven-membered azepino-indole skeleton through the PS reaction was revealed at the atomic level by quantum chemical calculations. The structures of the transition states and intermediates involved in the reaction pathway were optimized, and the energetics of the complete reaction were analyzed. Based on our calculation results, the most likely pathway of the enzyme-catalyzed reaction was determined, and the rate-determining step of the reaction was clarified. The mechanistic details obtained in the present study are important in understanding the promiscuous activity of RsSTR in the formation of the rare azepino-indole skeleton molecule and are also helpful in designing STR enzymes for the synthesis of other new alkaloid skeleton molecules.
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Alcaloides , Alcaloides de Vinca , Alcaloides de Vinca/química , EsqueletoRESUMO
Papuloerythroderma of Ofuji (PEO) is an uncommon disease characterised by widespread erythroderma composed of intensely pruritic solid papules coalescing into plaques sparing the skin folds (deck-chair sign). The pathogenesis of PEO remains unclear, although T helper (Th) 2 and Th22 cells may play an important role. Dupilumab is an interleukin (IL)-4 receptor α-antagonist that effectively reduces Th2 responses, which has drawn increasing attention in the treatment of PEO patients. Here, we reported a successful case of dupilumab treatment in combination with ultraviolet B (UVB) radiation therapy, which is well known and effective for chronic itch. The patient had a significant decrease in visual analogue scale (VAS) score and eosinophil after only 1 week of treatment, which may be due to the combination effect.
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Dermatite Esfoliativa , Dermatopatias Papuloescamosas , Terapia Ultravioleta , Humanos , Dermatopatias Papuloescamosas/patologia , Dermatite Esfoliativa/patologiaRESUMO
Psoriasis is a chronic inflammatory skin disease associated with multiple comorbidities and complex pathogenesis. Long non-coding RNAs (lncRNAs) play an important regulatory role in many diseases, including psoriasis. In this study, We aimed to investigate the role and mechanism of lncRNA GDA-1 (GDA) in M5-treated psoriatic keratinocytes. GDA expression was significantly upregulated in psoriatic tissues and M5-treated keratinocytes. By silencing and overexpressing GDA in NHEKs and Ker-CT cells, we showed that GDA regulated proliferation and cell cycle and increased secretion of interleukin-1ß (IL-1ß), IL-6, and chemokine ligands 2 and 20 (CCL2 and CCL20). RNA sequencing after GDA silencing led to the identification of a close regulatory relationship between GDA and Forkhead Box M1 (FOXM1). GDA significantly influenced FOXM1 expression at both mRNA and protein levels and activated STAT3/NF-κB signaling pathways. STAT3 and NF-κB inhibition abrogated GDA effects on keratinocyte proliferation and inflammation. In conclusion, our study is the first to report that Lnc-GDA-1 distinctly regulates FOXM1 expression and mediates proliferation and inflammation of psoriatic keratinocytes through the STAT3/NF-κB signaling pathway, which may be a potent target for psoriasis treatment.
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Psoríase , RNA Longo não Codificante , Humanos , NF-kappa B/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Psoríase/metabolismo , Transdução de Sinais , Queratinócitos/metabolismo , Inflamação/metabolismo , Proliferação de Células , Fator de Transcrição STAT3/metabolismoRESUMO
One-step purification of ethylene (C2 H4 ) from a quaternary gas mixture of C2 H6 /C2 H4 /C2 H2 /CO2 by adsorption is a promising separation process, yet developing adsorbents that synergistically capture various gas impurities remains challenging. Herein, a Lego-brick strategy is proposed to customize pore chemistry in a unified framework material. The ethane-selective MOF platform is further modified with customized binding sites to specifically adsorb acetylene and carbon dioxide, thus one-step purification of C2 H4 with high productivity of polymer-grade product (134 mol kg-1 ) is achieved on the assembly of porous coordination polymer-2,5-furandicarboxylic acid (PCP-FDCA) and PCP-5-aminoisophthalic acid (IPA-NH2 ). Computational studies verify that the low-polarity surface of this MOFs-based platform provides a delicate environment for C2 H6 recognition, and the specific binding sites (FDCA and IPA-NH2 ) exhibit favorable trapping of C2 H2 and CO2 via CHδ+ ···Oδ- and Cδ+ ···Nδ- electrostatic interactions, respectively. The proposed Lego-brick strategy to customize binding sites within the MOFs structure provides new ideas for the design of adsorbents for compounded separation tasks.
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The anammox-based process has been considered a promising biological nitrogen elimination method for the treatment of nitrogen-rich wastewater ever since its discovery 40 years ago. However, the slow growth rate of anammox bacteria and severe sludge washout result in a long startup period and limit its widespread industrial application. A membrane bioreactor (MBR) is considered an ideal reactor for the operation of the anammox-based process because the membranes allow for 100 % biomass retention. According to a systematic review of the literature, anammox-based MBR is becoming a research hotspot in the field of nitrogen wastewater treatment. The fundamental understanding of anammox-based MBR and its membrane fouling situation is essential for the development and application of anammox-based MBR. In this paper, the application of MBR in different kinds of anammox process are reviewed. The membrane fouling mechanism and strategies to control membrane fouling are also proposed. It is expected that this review will serve as an invaluable guide for future research and in the engineering applications of anammox-based MBR process.
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Oxidação Anaeróbia da Amônia , Reatores Biológicos , Reatores Biológicos/microbiologia , Esgotos/microbiologia , Águas Residuárias , Nitrogênio , Membranas ArtificiaisRESUMO
A novel two-stage process comprising pre-denitrification and single-stage partial nitritation/anammox was developed to treat swine manure digestate with a constant nitrogen loading rate of 1.0 gN/L/d. As the influent NH4+-N concentration increased from 500 to 1500 mg/L, a nitrogen removal efficiency of 88 %-96 % and 5-day biochemical oxygen demand removal efficiency of 93 %-97 % were achieved. Owing to the high influent chemical oxygen demand (COD)/nitrates and nitrites (NOX) ratio of 8.2-9.2 and high COD utilization of denitrifying bacteria (DB), the NO2--N and NO3--N removal efficiencies in the denitrification reactor reached 96 %-99 % and 97 %-99 %, respectively. The contribution of anammox bacteria to nitrogen removal was 70.9 %-84.3 %, whereas that of DB was 11.7 %-18.3 %. The contributions of DB and ordinary heterotrophic organisms to COD removal were 19.5 %-49.3 % and 17.9 %-39 %, respectively. This study will help guide the anammox process in swine wastewater treatment.
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Desnitrificação , Nitrogênio , Suínos , Animais , Esterco , Reatores Biológicos/microbiologia , Oxidação Anaeróbia da Amônia , Oxirredução , Bactérias , Águas Residuárias/microbiologia , EsgotosRESUMO
The development of adsorption-based separation processes alternative to the energy-intensive cryogenic distillation for a mixture of propylene and propane remains essential but challenging in gas industries. Molecular sieving separation of C3H6/C3H8 on stable carbon adsorbents appeals to be promising, while it is quite challenging to realize due to the random distributions and arrangements of the internal pores in common carbons. Herein, a series of polysaccharide-based CD-MOF-derived ultramicroporous carbon adsorbents with their pore size tuned at a subangstrom level were prepared. Molecular sieving separation of C3H6/C3H8 was realized on the optimal C-CDMOF-2-700 owing to the delicate structure with an appropriate pore size (5.0 Å). Besides, C-CDMOF-2-700 exhibited a high C3H6 uptake of 1.97 mmol g-1 under ambient conditions. An ultrahigh uptake ratio of C3H6/C3H8 at 1.0 kPa (403) was also achieved, outperforming all reported adsorbents. Kinetic adsorption tests and breakthrough experiments further demonstrate this well-designed carbon adsorbent to be promising in industrial C3H6/C3H8 separation.
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The current study aimed to investigate the role and underlying mechanism of Resolvin D1 (RvD1) alleviating spinal nerve ligation (SNL)-induced neuropathic pain (NP) and its interplay with regulatory cascades of Nod-like Receptor Protein 3 (NLRP3) inflammasome. Sprague-Dawley male rat models of SNL-stimulated NP were established, which were pre-treated with different doses of RvD1, WRW4 (ALX/FPR2 inhibitor) or U0126 (ERK inhibitor) for three successive days following the operation. Pain behavior was assessed by measuring changes in the mechanical sensitivity of the hind paws during an observation period of seven consecutive days. The spinal cord (SC) and dorsal root ganglions (DRGs) tissues were collected on postoperative day 7. Immunohistochemistry (IHC) and Western blot were performed to determine the expression levels of NLRP3 inflammasome complex, ALX/FPR2 receptor and extracellular signal-related kinase (ERK). The pro-inflammatory mediators (IL-1ß and IL-18) were measured by enzyme-linked immunosorbent assay (ELISA). The results showed that RvD1 could alleviate mechanical allodynia significantly in the SNL-induced NP rat models. Also, RvD1 inhibited the expression of p-ERK, the NLRP3 inflammasomes complex and its corresponding downstream pro-inflammatory mediators which were significantly enhanced in the SC and DRGs of the rat SNL models. While these changes were partially reversed by pre-administration of WRW4 and further strengthened by co-treated with U0126. Our results suggest that RvD1 dependent on ALX/FPR2 may have an analgesic and anti-inflammatory influence on SNL-induced NP driven by inhibiting NLRP3 inflammasome via ERK signaling pathway. These data also provide strong support for the recent modulation of neuro-inflammatory priming and highlight the potential for specialized pro-resolving mediators (SPMs) as novel therapeutic avenues for NP.
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Ácidos Docosa-Hexaenoicos , Hiperalgesia , Neuralgia , Animais , Ácidos Docosa-Hexaenoicos/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Hiperalgesia/tratamento farmacológico , Inflamassomos , Mediadores da Inflamação , Masculino , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Neuralgia/tratamento farmacológico , Ratos , Ratos Sprague-Dawley , Receptores de Lipoxinas/metabolismoRESUMO
A simultaneous partial nitritation, anammox, denitrification, and COD oxidation (SNADCO) process was used to evaluate the nitrogen and biodegradable organic matter removal of swine manure digestate based on a nitrite limitation and ammonium surplus strategy. As influent ammonium concentration increased from 500 mg/L to 2100 mg/L, the 5 day biochemical oxygen demand (BOD5) maintained at a high removal efficiency of 95.4%. However, nitrogen removal efficiency (NRE) decreased from 90.9% to 68.2% due to the inhibition of AnAOB caused by an ammonium concentration of 2100 mg/L. The contribution of AnAOB to nitrogen removal was 75.6-86.5%, while that of denitrifying bacteria was 4.6-7.0%. In the case of COD removal, the contributions were from ordinary heterotrophic organisms and denitrifying bacteria, at 27.1-64.9% and 11.2-22.1%, respectively. The results of specific bacteria activity tests and microbial analysis showed that a highly efficient synergism between functional microorganisms is essential for the stability of the SNADCO process.
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Compostos de Amônio , Nitrogênio , Animais , Bactérias , Reatores Biológicos/microbiologia , Desnitrificação , Esterco , Oxirredução , Esgotos/microbiologia , Suínos , Águas Residuárias/químicaRESUMO
BACKGROUND: Dysregulation of miR-486-3p was related to the growth and development of a variety of cancers, but the specific function of miR-486-3p in cutaneous squamous cell carcinoma (cSCC) is not to be confirmed yet. OBJECTIVE: Our present study aimed to validate the potential molecular mechanisms of miR-486-3p in cSCC and the potential of miR-486-3p as a novel target for future treatment. METHODS: Human cSCC samples and normal skin tissues were applied to determine the expression level of miR-486-3p and FLOT2 by fluorescence in situ hybridization (FISH) and quantitative reverse transcription PCR (qRT-PCR), respectively. As well as BALB/C nude mouse tumor model, three cSCC cells lines including HSC-1, HSC-5 and A431 were utilized to demonstrate the potential function of miR-486-3p and FLOT2 in tumorigenesis. RESULTS: Our experimental results showed that miR-486-3p was highly expressed both in tumor samples and cell lines of cSCC. Upregulation of miR-486-3p enhanced the proliferation and migration ability of cSCC cell lines and promoted tumorigenicity in vivo. Furthermore, we confirmed that FLOT2 was a direct targeted gene of miR-486-3p. In contrary to the expression level of miR-486-3p, FLOT2 was low expressed in cSCC patient specimens and cell lines. Knockdown of FLOT2 promoted tumorigenesis of cSCC; whereas FLOT2 reversed the tumor-promoting effect of miR-486-3p. CONCLUSION: Our data exhibited that miR-486-3p exerted its effects on carcinogenesis as an oncogene in cSCC via suppression of FLOT2. This discovery will develop new therapeutic targets of cSCC.
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Carcinoma de Células Escamosas/etiologia , Proteínas de Membrana/metabolismo , MicroRNAs/metabolismo , Neoplasias Cutâneas/etiologia , Adulto , Idoso , Animais , Carcinogênese , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/terapia , Linhagem Celular Tumoral , Feminino , Humanos , Masculino , Camundongos Nus , MicroRNAs/antagonistas & inibidores , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Metástase Neoplásica , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/terapia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Accumulated evidence has demonstrated causative links between neuropathic pain (NP) and immune-mediated inflammatory disorders. However, the role of inflammasome-induced pyroptosis in NP remains elusive. Melatonin possesses a well-documented analgesic action in various pain models. The current study aimed to test our hypothesis that melatonin regulated pyroptosis to alleviate NP by inhibiting NF-κB/NLRP3-dependent signaling. A rat model of spinal nerve ligation (SNL) was established to explore the potential association between melatonin and pyroptosis. Behavioral experiments revealed that SNL provoked severe allodynia which was suppressed by the administration of melatonin, a caspase-1 inhibitor (VX-765), or an NF-κB inhibitor (BAY 11-7085). SNL significantly up-regulated the inflammatory cytokines associated with the excessive activation of NLRP3 components and NF-κB signaling, as well as a marked pyroptosis activation. These effects were partially inhibited by melatonin, VX-765 or BAY 11-7085, and when melatonin and inhibitors were added together, the effect was enhanced. In conclusion, melatonin has potent analgesic and anti-inflammatory effects in SNL models through preventing pyroptosis via the NF-κB/NLRP3 inflammasome signaling pathway.
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Inflamassomos , Melatonina , Animais , Inflamassomos/metabolismo , Melatonina/farmacologia , Melatonina/uso terapêutico , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose , Ratos , Transdução de Sinais , Nervos Espinhais/metabolismoRESUMO
The purpose of this study was to investigate the performance of the thermophilic and mesophilic anaerobic digestion process (TADP, MADP) fed with NaOH-microwave pretreated waste activated sludge. The experiment was conducted in anaerobic CSTR reactors. During this experiment, the reactors were stable in operation and were not inhibited by ammonia. The methane production and reduction of organic matters from MADP were less than those from TADP. The dewatering performance of mesophilic sludge was better than that of the thermophilic sludge. The experimental results showed that the continuous TADP and MADP were effective, when the reactors were fed with the waste activated sludge pretreated by NaOH-microwave. MADP was more suitable to combine the NaOH-MW pretreatment process than TADP.