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The effectiveness of SARS-CoV-2 vaccines and therapeutic antibodies have been limited by the continuous emergence of viral variants and by the restricted diffusion of antibodies from circulation into the sites of respiratory virus infection. Here, we report the identification of two highly conserved regions on the Omicron variant receptor-binding domain recognized by broadly neutralizing antibodies. Furthermore, we generated a bispecific single-domain antibody that was able to simultaneously and synergistically bind these two regions on a single Omicron variant receptor-binding domain as revealed by cryo-EM structures. We demonstrated that this bispecific antibody can be effectively delivered to lung via inhalation administration and exhibits exquisite neutralization breadth and therapeutic efficacy in mouse models of SARS-CoV-2 infections. Importantly, this study also deciphered an uncommon and highly conserved cryptic epitope within the spike trimeric interface that may have implications for the design of broadly protective SARS-CoV-2 vaccines and therapeutics.
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Vacunas contra la COVID-19 , Anticuerpos de Dominio Único , Administración por Inhalación , Animales , Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19 , Vacunas contra la COVID-19/administración & dosificación , Modelos Animales de Enfermedad , Humanos , Ratones , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus/químicaRESUMEN
Premature ovarian insufficiency (POI) is one of the important causes of female infertility. Yet the aetiology for POI is still elusive. FBXW7 (F-box with 7 tandem WD) is one of the important components of the Skp1-Cullin1-F-box (SCF) E3 ubiquitin ligase. FBXW7 can regulate cell growth, survival and pluripotency through mediating ubiquitylation and degradation of target proteins via triggering the ubiquitin-proteasome system, and is associated with tumorigenesis, haematopoiesis and testis development. However, evidence establishing the function of FBXW7 in ovary is still lacking. Here, we showed that FBXW7 protein level was significantly decreased in the ovaries of the cisplatin-induced POI mouse model. We further showed that mice with oocyte-specific deletion of Fbxw7 demonstrated POI, characterized with folliculogenic defects, early depletion of follicle reserve, disordered hormonal secretion, ovarian dysfunction and female infertility. Impaired oocyte-GCs communication, manifested as down-regulation of connexin 37, may contribute to follicular development failure in the Fbxw7-mutant mice. Furthermore, single-cell RNA sequencing and in situ hybridization results indicated an accumulation of Clu and Ccl2 transcripts, which may alter follicle microenvironment deleterious to oocyte development and accelerate POI. Our results establish the important role of Fbxw7 in folliculogenesis and ovarian function, and might provide valuable information for understanding POI and female infertility.
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Proteína 7 que Contiene Repeticiones F-Box-WD , Oocitos , Folículo Ovárico , Insuficiencia Ovárica Primaria , Animales , Femenino , Insuficiencia Ovárica Primaria/genética , Insuficiencia Ovárica Primaria/metabolismo , Insuficiencia Ovárica Primaria/patología , Proteína 7 que Contiene Repeticiones F-Box-WD/metabolismo , Proteína 7 que Contiene Repeticiones F-Box-WD/genética , Oocitos/metabolismo , Ratones , Folículo Ovárico/metabolismo , Folículo Ovárico/crecimiento & desarrollo , Folículo Ovárico/patología , Modelos Animales de Enfermedad , Eliminación de Gen , Ratones Noqueados , Infertilidad Femenina/genética , Infertilidad Femenina/metabolismo , Infertilidad Femenina/patología , Cisplatino/efectos adversosRESUMEN
The high water solubility and ecotoxicity of thiamethoxam (TMX) is a potential hazard to ecosystems and human health. Here, a strain of Bacillus cereus with high TMX degradation activity was isolated from the sediment of the A2O process in the wastewater treatment plant and was able to utilize TMX as its sole carbon source. Under different environmental conditions, the degradation efficiency of TMX by Bacillus cereus-S1 (strain S1) ranged from 41.0% to 68.9% after 216 h. The optimum degradation conditions were DO = 3.5 mg/L and pH 9.0. The addition of an appropriate carbon-to-nitrogen ratio could accelerate the degradation of TMX. A plausible biodegradation pathway has been proposed based on the identified metabolites and their corresponding degradation pathways. TMX can be directly converted into Clothianidin (CLO), TMX-dm-hydroxyl and TMX-Urea by a series of reactions such as demethylation, oxadiazine ring cleavage and C=N substitution by hydroxy group. The main products were TMX-dm-hydroxyl and TMX-Urea, the amount of CLO production is relatively small. This study aims to provide a new approach for efficient degradation of TMX; furthermore, strain S1 is a promising biological source for in situ remediation of TMX contamination.
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Guanidinas , Insecticidas , Neonicotinoides , Tiazoles , Humanos , Tiametoxam , Insecticidas/toxicidad , Aguas del Alcantarillado , Bacillus cereus/metabolismo , Ecosistema , Nitrocompuestos/toxicidad , Nitrocompuestos/metabolismo , Oxazinas/metabolismo , Oxazinas/toxicidad , Carbono , UreaRESUMEN
The Partial nitritation-Anammox (PN/A) process can be restricted when treating high ammonia nitrogen wastewater containing antibiotics. This study aims to explore the response mechanism of the PN/A process under antibiotic stress. Results showed the PN/A process achieved a nitrogen removal rate higher than 1.01 ± 0.03 kg N/m3/d under long-term sulfamethazine stress. The increase of extracellular polymers from 22.52 to 43.96 mg/g VSS was conducive to resisting antibiotic inhibitory. The increase of Denitratisoma and SM1A02 abundance as well as functional genes nirS and nirK indicated denitrifiers should play an important role in the stability of the PN/A system under sulfamethazine stress. In addition, antibiotic-resistant genes (ARGs) sul1 and intI1 significantly increased by 8.78 and 5.12 times of the initial values to maintain the resistance of PN/A process to sulfamethazine stress. This study uncovers the response mechanism of the PN/A process under antibiotic stress, offering a scientific basis and guidance for further application in the future.
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Antibacterianos , Antibacterianos/farmacología , Microbiota/efectos de los fármacos , Reactores Biológicos , Aguas Residuales/microbiología , Eliminación de Residuos Líquidos/métodos , Nitrógeno/metabolismoRESUMEN
Calcium ions (Ca2+) play crucial roles in sperm motility and fertilization. The copine (CPNE) family comprises several Ca2+-dependent phospholipid-binding proteins. Of these, CPNE1 is extensively expressed in mammalian tissues; however, its precise role in testicular development and spermatogenesis is yet to be fully characterized. In this study, we used proteomics to analyze testicular biopsies and found that levels of CPNE1 were significantly reduced in patients with non-obstructive azoospermia (defective spermatogenesis) compared to those in patients with obstructive azoospermia (physiological spermatogenesis). In mice, CPNE1 is expressed at various stages of germ cell development and is associated with the Golgi apparatus. Ultimately, CPNE1 is expressed in the flagella of mature sperms. To further examine the role of CPNE1, we developed a Cpne1 knockout mouse model. Analysis showed that the loss of Cpne1 did not impair testicular development, spermatogenesis, or sperm morphology and motility in physiological conditions. When treated with gadolinium (III) chloride or 2-aminoethoxydiphenyl borate, known inhibitors of store-operated Ca2+ entry, Ca2+ signals and sperm motility were significantly compromised in wild-type mice; however, both mechanisms were conserved in KO mice. These results suggested that CPNE1 is dispensable for testicular development, spermatogenesis or sperm motility in physiological conditions. In addition, CPNE1 may represent a target of Ca2+ channel inhibitors and may therefore be implicated in the regulation of Ca2+ signaling and sperm motility.
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The continuous emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants poses new challenges in the fight against the coronavirus disease 2019 (COVID-19) pandemic. The newly emerging Omicron strain caused serious immune escape and raised unprecedented concern all over the world. The development of an antibody targeting a conserved and universal epitope is urgently needed. A subset of neutralizing antibodies (NAbs) against COVID-19 from convalescent patients were isolated in our previous study. In this study, we investigated the accommodation of these NAbs to SARS-CoV-2 variants of concern (VOCs), revealing that IgG 553-49 neutralizes pseudovirus of the SARS-CoV-2 Omicron variant. In addition, we determined the cryo-electron microscopy (cryo-EM) structure of the SARS-CoV-2 spike (S) protein complexed with three monoclonal antibodies targeting different epitopes, including 553-49, 553-15, and 553-60. Notably, 553-49 targets a novel conserved epitope and neutralizes the virus by disassembling S trimers. IgG 553-15, an antibody that neutralizes all of the VOCs except Omicron, cross-links two S trimers to form a trimer dimer, demonstrating that 553-15 neutralizes the virus by steric hindrance and virion aggregation. These findings suggest the potential to develop 553-49 and other antibodies targeting this highly conserved epitope as promising therapeutic reagents for COVID-19. IMPORTANCE The emergence of the Omicron strain of SARS-CoV-2 caused higher immune escape, raising unprecedented concerns about the effectiveness of antibody therapies and vaccines. In this study, we identified a SARS-CoV-2 neutralizing antibody, 553-49, which neutralizes all variants by targeting a completely conserved novel epitope. In addition, we revealed that IgG 553-15 neutralizes SARS-CoV-2 by cross-linking virions and that 553-60 functions by blocking receptor binding. Comparison of different receptor binding domain (RBD) epitopes revealed that the 553-49 epitope is hidden in the S trimer and keeps a high degree of conservation during SARS-CoV-2 evolution, making 553-49 a promising therapeutic reagent against the emerging Omicron and future variants of SARS-CoV-2.
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COVID-19 , SARS-CoV-2 , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Microscopía por Crioelectrón , Epítopos , Humanos , Inmunoglobulina G , Pruebas de Neutralización , SARS-CoV-2/genética , Glicoproteína de la Espiga del Coronavirus/genéticaRESUMEN
Emergence of various circulating SARS-CoV-2 variants of concern (VOCs) promotes the identification of pan-sarbecovirus vaccines and broadly neutralizing antibodies (bNAbs). Here, to characterize monoclonal antibodies cross-reactive against both SARS-CoV-1 and SARS-CoV-2 and to search the criterion for bNAbs against all emerging SARS-CoV-2, we isolated several SARS-CoV-1-cross-reactive monoclonal antibodies (mAbs) from a wildtype SARS-CoV-2 convalescent donor. These antibodies showed broad binding capacity and cross-neutralizing potency against various SARS-CoV-2 VOCs, including B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), and B.1.617.2 (Delta), but failed to efficiently neutralize Omicron variant and its sublineages. Structural analysis revealed how Omicron sublineages, but not other VOCs, efficiently evade an antibody family cross-reactive against SARS-CoV-1 through their escape mutations. Further evaluation of a series of SARS-CoV-1/2-cross-reactive bNAbs showed a negative correlation between the neutralizing activities against SARS-CoV-1 and SARS-CoV-2 Omicron variant. Together, these results suggest the necessity of using cross-neutralization against SARS-CoV-1 and SARS-CoV-2 Omicron as criteria for rational design and development of potent pan-sarbecovirus vaccines and bNAbs.
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COVID-19 , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo , Vacunas , Humanos , SARS-CoV-2 , Anticuerpos Neutralizantes , Anticuerpos Monoclonales , Anticuerpos ampliamente neutralizantes , Anticuerpos Antivirales , Glicoproteína de la Espiga del CoronavirusRESUMEN
Kelch-like protein 6 (KLHL6) plays a critical role in preventing the development and survival of diffuse large B-cell lymphoma (DLBCL) through its involvement in the ubiquitin proteasome system. Specifically, KLHL6 binds to cullin3 (Cul3) and the substrate, facilitating the assembly of the E3 ligase responsible for substrate ubiquitination. It is imperative to investigate the precise function of KLHL6 by conducting a structural analysis of its interaction with Cul3. Here, we present the expression, purification, and characterization of the full-length KLHL6. Our findings demonstrate that the addition of a Sumo-tag significantly enhances the production of KLHL6, while also improving its stability and solubility. Moreover, through gel filtration and negative staining electron microscopy (EM), we observed that KLHL6 adopts a homomultimeric form in solution. Additionally, we found that the presence of Cul3NTD enhances the stability and homogeneity of KLHL6 by forming a complex. Consequently, the successful expression and purification of full-length KLHL6 serve as a foundation for further investigations into the structure and function of the KLHL6/Cullin3/Rbx1 substrate complex, as well as provide a potential strategy for studying other proteins within the KLHL family that possess similar characteristics.
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Ubiquitina-Proteína Ligasas , Ubiquitina , Ubiquitina/metabolismo , Ubiquitinación , Ubiquitina-Proteína Ligasas/metabolismo , MutaciónRESUMEN
With the shortage of phosphorus resources, the concept of phosphorus recovery from wastewater is generally proposed. Recently, phosphorus recovery from wastewater in the form of vivianite has been widely reported, which could be used as a slow-release fertilizer as well as the production of lithium iron phosphate for Li-ion batteries. In this study, chemical precipitation thermodynamic modeling was applied to evaluate the effect of solution factors on vivianite crystallization with actual phosphorus containing industrial wastewater. The modeling results showed that the solution pH influences the concentration of diverse ions, and the initial Fe2+ concentration affects the formation area of vivianite. The saturation index (SI) of vivianite increased with the initial Fe2+ concentration and Fe:P molar ratio. pH 7.0, initial Fe2+ concentration 500 mg/L and Fe:P molar ratio 1.50 were the optimal conditions for phosphorus recovery. Mineral Liberation Analyzer (MLA) accurately determined the purity of vivianite was 24.13%, indicating the feasibility of recovering vivianite from industrial wastewater. In addition, the cost analysis showed that the cost of recovering phosphorus by the vivianite process was 0.925 USD/kg P, which can produce high-value vivianite products and realize "turn waste into treasure".
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Fósforo , Aguas Residuales , Fosfatos/química , Compuestos Ferrosos , Eliminación de Residuos Líquidos , Aguas del AlcantarilladoRESUMEN
The overuse of thiamethoxam (THM) has threatened the survival of living organisms and it is necessary to find an environmentally friendly material to remove THM frequently detected in water. Biochar prepared from cow manure modified with ZnCl2 (Zn-CBC) was used to remove THM. Compared to the unmodified cow manure biochar (CBC), the removal ratio of THM by Zn-CBC was enhanced 35 times. In the mechanistic analysis, SEM and BET showed that Zn-CBC had a good pore structure and its specific surface area (166.502 m2 g-1) increased to 17 times that of CBC, indicating that Zn-CBC had good pore adsorption properties. The adsorption kinetic and isotherm implied that the main mechanism was chemisorption including π-π interaction and H-bonding. Furthermore, the stable graphitized structure of Zn-CBC allowed for efficient adsorption and reusability. In addition, this study constructed an intelligent prediction model using batch experiment data, and the high R2 (0.978) and low RMSE (0.057) implied that the model could accurately and quantitatively predict the adsorption efficiency. This paper provides a novel perspective to simultaneously remove the neonicotinoid insecticides and realize the resource utilization of cow manure.
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For the sake of exploring a new economical and low-carbon alternative for real nitrate-containing wastewater treatment, a new combined partial denitrification-anammox with urea hydrolysis (U-PD-Anammox) process was developed. The nitrogen removal performance of this process was investigated through long-term operation in a sequencing batch reactor (SBR) and two submerged anaerobic biological filters (SABF). Results showed that the average NO3--N to NO2-N transformation ratio improved to 82.6% with organic carbon source to NO3-N ratio of 1.8, and urea hydrolysis provided sufficient NH4+-N and inorganic carbon to anammox process for nitrogen removal. The influent NH4+-N/NO2--N ratio for subsequent anammox reactor could be adjacent to the optimal ratio of 1.32 during the whole operation. The combined process showed efficient nitrogen removal performance with 85% NO3--N removal, 93.8% total nitrogen removal and total nitrogen loading rate as 1.1 ± 0.5 kg N/(m3·d). High-throughput sequencing analysis results revealed that Genera Thauera, Hyphomicrobium and Candidatus Brocadia were the dominant species responsible for partial denitrification, urea hydrolysis and anammox, respectively. The proposed process was more economically and environmental-friendly than the traditional denitriï¬cation process with 51.7% operational cost reduction, 99.7% N2O and 60% CO2 emission decrement, facilitating the sustainable development of the nitrate-containing wastewater treatment industry in the future.
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Nitratos , Purificación del Agua , Carbono , Urea , Desnitrificación , Hidrólisis , Oxidación Anaeróbica del Amoníaco , Dióxido de Nitrógeno , Óxidos de Nitrógeno , NitrógenoRESUMEN
The nitrogen pollution control of liquid-ammonia mercerization wastewater (LMWW) is one of the typical obstacle restricting the sustainability of textile industry. In this study, a 500 kg N/day two-stage partial nitritation/anammox (PN/A) process containing PN reactor filled with zeolite and biofilm anammox reactors was successfully started up in 45 days and operated stably with high shock resistance over one year for LMWW treatment. The large-scale process achieved an average ammonium removal efficiency (94.3 ± 2.3%), total nitrogen removal efficiency (89.4 ± 2.7%) and nitrogen removal rate (1.003 ± 0.386 kg N/m3/day) during one year engineering operation. Simultaneous denitrification was revealed by the contribution of 5.2% total nitrogen removed. High-throughput sequencing results showed that Nitrosomonas was the most dominant genus in PN reactor, and Ca. Anammoxoglobus and Ca. Kuenenia were the functional bacteria for nitrogen removal in anammox reactors. Compared to traditional nitrification-denitrification process, the large-scale process reduced a total operational cost of 46.03 CNY/kg N for LMWW. This study revealed the proposed process was quite reliable with fast start-up and high impact resistance to overcome the obstacle of nitrogen pollution control for LMWW economically and conducive to the sustainable development for textile industry.
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Compuestos de Amonio , Aguas Residuales , Desnitrificación , Amoníaco , Reactores Biológicos/microbiología , Oxidación Anaeróbica del Amoníaco , Oxidación-Reducción , Nitrógeno , Aguas del AlcantarilladoRESUMEN
Free nitrous acid (FNA) is a critical metric for stabilization of ANAMMOX but can not be directly and immediately measured by sensors or chemical measurement method, which hinders the effective management and operation for ANAMMOX. This study focuses on FNA prediction using hybrid model based on temporal convolutional network (TCN) combined with attention mechanism (AM) optimized by multiobjective tree-structured parzen estimator (MOTPE), called MOTPE-TCNA. A case study in an ANAMMOX reactor is carried out. Results show that nitrogen removal rate (NRR) is highly correlated with FNA concentration, indicating that it can forecast the operational status by predicting FNA. Then, MOTPE successfully optimizes the hyperparameters of TCN, helping TCN achieve a high prediction accuracy, and AM furtherly improves model accuracy. MOTPE-TCNA obtains the highest prediction accuracy, whose R2 value gets 0.992, increasing 1.71-11.80% compared to other models. As a deep neural network model, MOTPE-TCNA has more advantages than traditional machine learning methods in FNA prediction, which is beneficial to maintain the stable operation and easy control for ANAMMOX process.
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Oxidación Anaeróbica del Amoníaco , Ácido Nitroso , Reactores Biológicos , Nitrógeno , Oxidación-ReducciónRESUMEN
Simultaneous anammox and denitrification (SAD) is an efficient approach to treat wastewater having a low C/N ratio; however, few studies have investigated a combination of SAD and partial nitritation (PN). In this study, a lab-scale up-flow blanket filter (UBF) and zeolite sequence batch reactor (ZSBR) were continuously operated to implement SAD and PN advantages, respectively. The UBF achieved a high total nitrogen (TN) removal efficiency of over 70% during the start-up stage (days 1-50), and reached a TN removal efficiency of 96% in the following 90 days (days 51-140) at COD/NH4+-N ratio of 2.5. The absolute abundance of anammox bateria increased to the highest value of 1.58 × 107 copies/µL DNA; Comamonadaceae was predominant in the UBF at the optimal ratio. Meanwhile, ZSBR was initiated on day 115 as fast nitritation process to satisfy the influent requirement for the UBF. The combined process was started on day 140 and then lasted for 30 days, during the combined process, between the two reactors, the UBF was the main contributor for TN (66.5% ± 4.5%) and COD (71.8% ± 4.9%) removal. These results demonstrated that strong SAD occurred in the UBF when following a ZSBR with in-situ NOB elimination. This research presents insights into a novel biological nitrogen removal process for low C/N ratio wastewater treatment.
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Nitrógeno , Zeolitas , Desnitrificación , Reactores Biológicos , Oxidación Anaeróbica del Amoníaco , Oxidación-Reducción , Aguas Residuales , Aguas del AlcantarilladoRESUMEN
In mammals, testis development is triggered by the expression of the sex-determining Y-chromosome gene SRY to commit the Sertoli cell (SC) fate at gonadal sex determination in the fetus. Several genes have been identified to be required to promote the testis pathway following SRY activation (i.e., SRY box 9 (SOX9)) in an embryo; however, it largely remains unknown about the genes and the mechanisms involved in stabilizing the testis pathway after birth and throughout adulthood. Herein, we report postnatal males with SC-specific deletion of Raptor demonstrated the absence of SC unique identity and adversely acquired granulosa cell-like characteristics, along with loss of tubular architecture and scattered distribution of SCs and germ cells. Subsequent genome-wide analysis by RNA sequencing revealed a profound decrease in the transcripts of testis genes (i.e., Sox9, Sox8, and anti-Mullerian hormone (Amh)) and, conversely, an increase in ovary genes (i.e., LIM/Homeobox gene 9 (Lhx9), Forkhead box L2 (Foxl2) and Follistatin (Fst)); these changes were further confirmed by immunofluorescence and quantitative reverse-transcription polymerase chain reaction. Importantly, co-immunofluorescence demonstrated that Raptor deficiency induced SCs dedifferentiation into a progenitor state; the Raptor-mutant gonads showed some ovarian somatic cell features, accompanied by enhanced female steroidogenesis and elevated estrogen levels, yet the zona pellucida 3 (ZP3)-positive terminally feminized oocytes were not observed. In vitro experiments with primary SCs suggested that Raptor is likely involved in the fibroblast growth factor 9 (FGF9)-induced formation of cell junctions among SCs. Our results established that Raptor is required to maintain SC identity, stabilize the male pathway, and promote testis development.
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Rapaces , Células de Sertoli , Animales , Hormona Antimülleriana/genética , Estrógenos/metabolismo , Femenino , Factor 9 de Crecimiento de Fibroblastos/genética , Folistatina/genética , Regulación del Desarrollo de la Expresión Génica , Proteínas con Homeodominio LIM/genética , Masculino , Mamíferos/genética , Ratones , Rapaces/genética , Rapaces/metabolismo , Factor de Transcripción SOX9/genética , Células de Sertoli/metabolismo , Procesos de Determinación del Sexo/genética , Testículo/metabolismo , Factores de Transcripción/genéticaRESUMEN
The coupled process of thiosulfate-driven denitrification (NO3-âNO2-) and Anammox (TDDA) was a promising process for the treatment of wastewater containing NH4+-N and NO3--N. However, the high concentration of SO42- production limited its application, which needs to be alleviated by an economical and effective way to promote the application of TDDA process. In this study, TDDA process was started in a relatively short time by stepwise replacing nitrite with nitrate and operated continuously for 146 days. Results presented that the average total nitrogen removal efficiency of 82.18% can be acquired at a high loading rate of 1.98 kg N/(m3·d) with maximum nitrogen removal efficiency up to 87.04%. It was observed that the increase of S/N ratio improved the denitrification efficiency and slightly inhibit the Anammox process. Batch tests showed that Sulfammox process appeared in TDDA process under certain conditions, further contributing 2.59% nitrogen removal and 10.46% sulfur removal (14.42 mg/L NH4+-N and 37.68 mg/L SO42--S were removed). This finding was mainly attributed to the reduction of sulfate in TDDA system to elemental S0 or HS-, which subsequently was used as an electron donor to realize the recycling of sulfate (SO42--S) pollutants and promote the sulfur-nitrogen (S-N) cycle. High-throughput analysis displayed that Anammox bacteria (Candidatus_Kuenenia), Sulfur-oxidizing bacteria (Thiobacillus) with relatively high abundance of 5.37%, 7.74%, respectively, guaranteeing the excellent nitrogen and sulfate removal performance in the reactor. The enrichment of phyla Chloroflexi (31.79%), Proteobacteria (31.82%), class Ignavibacteriales (10.55%), genus Planctomycetes (13.57%) further verified the exitence of Sulfammox process in the TDDA reactor. This study provides a new perspective for the practical application of TDDA in terms of reducing the production of high concentration SO42- and saving operational cost and strengthening deeply nitrogen removal.
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Desnitrificación , Nitrógeno , Oxidación Anaeróbica del Amoníaco , Bacterias , Reactores Biológicos , Nitrógeno/análisis , Oxidación-Reducción , Aguas del Alcantarillado , Sulfatos , Azufre , Tiosulfatos , Aguas Residuales/análisisRESUMEN
Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by autoimmune-mediated platelet destruction and impaired platelet production, which can lead to an increased risk of bleeding. The clinical management of ITP currently remains a challenge for hematologists. We explored the role of interleukin-9 (IL-9) in the treatment of CD41-induced ITP, and investigated its underlying mechanisms in a CD41-induced ITP mouse model. IL-9 treatment increased the numbers of mature megakaryocytes (CD41+CD42d+) and CD41+Sca-1+ cells in the bone marrow in these model mice, while IL-9 receptor (IL-9R) small interfering RNA (siRNA) inhibited the process. Moreover, phosphorylated signal transducer and activator of transcription 5 (STAT5), as a downstream molecule of IL-9R, was increased after IL-9 treatment. We next investigated the source of IL-9 in bone marrow, osteoblasts produced the highest level of IL-9. These results confirmed that IL-9 could prevent CD41-induced ITP in BALB/c mice by regulating osteoblasts and activating IL-9R/STAT5 signaling in megakaryocytes, thus providing further evidence for IL-9 as a promising therapeutic agent for the treatment of ITP.
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Interleucina-9/uso terapéutico , Quinasas Janus/metabolismo , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Factor de Transcripción STAT5/metabolismo , Transducción de Señal , Animales , Células Cultivadas , Interleucina-9/farmacología , Masculino , Megacariocitos/efectos de los fármacos , Megacariocitos/metabolismo , Ratones , Ratones Endogámicos BALB C , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Púrpura Trombocitopénica Idiopática/prevención & control , Receptores de Interleucina-9/metabolismoRESUMEN
Oligoasthenoteratozoospermia is a human infertility syndrome caused by defects in spermatogenesis, spermiogenesis, and sperm maturation, and its etiology remains unclear. Kelch-like 10 (KLHL10) is a component of ubiquitin ligase E3 10 (KLHL10) and plays an important role in male fertility. Deletion or mutation of the Klhl10 gene in Drosophila or mice results in defects in spermatogenesis or sperm maturation. However, the molecular mechanisms by which KLHL10 functions remain elusive. In this study, we identified a missense mutation (c.1528AâG, p.I510V) in exon 5 of KLHL10, which is associated with oligoasthenoteratozoospermia in humans. To investigate the effects of this mutation on KLHL10 function and spermatogenesis and/or spermiogenesis, we generated mutant mice duplicating the amino acid conversion using the clustered regularly interspaced palindromic repeat/caspase 9 (CRISPR/Cas9) system and designated them Klhl10I510V mice. However, the Klhl10I510V mice did not exhibit any defects in testis development, spermatogenesis, or sperm motility at ten-weeks-of-age, suggesting that this mutation does not disrupt the KLHL10 function, and may not be the cause of male infertility in the affected individual with oligoasthenoteratozoospermia.
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Péptidos y Proteínas de Señalización Intracelular/genética , Oligospermia/genética , Adulto , Animales , Humanos , Masculino , Ratones , Mutación MissenseRESUMEN
The adsorption process for low concentration phosphorus wastewater treatment has advantages of simple convenience, stable performance and less sludge, while most of current adsorbents fail to be separated for reuse. Meanwhile, few people pay attention to the removal of low concentration phosphorus from tail water by adsorbents. In this study, a newly efficient Fe-Mg-Zr layered double hydroxide beads were prepared by simple in-situ crosslinking method and applied for low concentration phosphorus adsorption from real tail water. The maximum adsorption capacity of Fe-Mg-Zr beads was 21.61 mg/g, showing more practical application value for phosphorus removal. Fixed bed experiments showed that 5.0 g adsorbent could removed 2.12 mg phosphorus from tail wastewater containing 1.03 mg/L phosphorus. The beads adsorbent can be reused with excellent adsorption performance even after five cycles of adsorption-desorption operation. After detailed analyses, it was found that ligand exchange and ion exchange were the dominant mechanisms for phosphorus adsorption by this beads. Overall, the material has the advantages of simple preparation, good adsorption performance, easy separation and recycle, indicating a great potential for low concentration phosphorus wastewater treatment.
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Contaminantes Químicos del Agua , Purificación del Agua , Adsorción , Humanos , Concentración de Iones de Hidrógeno , Hidróxidos , Cinética , Fósforo , Aguas Residuales , AguaRESUMEN
For the sake of high efficiency and saving operational cost for high-concentration urea wastewater treatment, a novel two-stage partial nitritation (PN)-anammox process containing simultaneous urea hydrolysis and PN in sequencing batch reactor (SBR) was investigated. Although the influent urea concentration increased from 500 to 1200 mg/L, the SBR simultaneously achieved urea removal efficiency higher than 98% and stable PN with effluent NO2--N/NH4+-N ratio of 1.0-1.3 without any extra alkalinity addition. The intracellular hydrolysis was the dominant mechanism for urea removal and persistent free ammonia inhibition on nitrite-oxidizing bacteria was the main reason for nitrite accumulation of 97.92% in SBR. The subsequent anammox reactor showed efficient nitrogen removal performance with average ammonium removal efficiency, nitrogen removal efficiency and maximum nitrogen removal loading rate of 98.08%, 81.45% and 1.05 kg N·m-3·d-1 respectively. High-throughput sequencing results indicated Gemmatimonadetes became the most abundant bacterial phylum related to potential intracellular urea hydrolysis and displayed obvious ammonium-oxidizing bacteria enrichment and nitrite-oxidizing bacteria inhibition in SBR, and the dominant anammox bacteria (Candidatus_Kuenenia) in anammox reactor. The proposed process was proven to be promising for high-concentration urea wastewater treatment, facilitating the sustainable development of the urea industry in the future.