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Protein-based subunit vaccines are weakly immunogenic, and developing self-adjuvanting vaccines with adjuvant conjugated to antigen is a promising approach for generating optimal immune responses. Here, we report a novel adjuvant-protein conjugate vaccine based on versatile oxime ligation technique. Firstly, the adjuvant properties of a series of TLR7 and TLR7/8 small molecule agonists in self-adjuvanting vaccines were systematically compared by coupling them to proteins in consistent ratio via p-carboxybenzaldehyde (p-CBA) for the first time. All conjugate vaccines induced cytokine secretion in murine and human macrophages in vitro, and promoted specific antibody production in vivo. Notably, a conjugate containing imidazoquinoline TLR7/8 agonist (TLR7/8a1) showed the greatest enhancement in Th1/2 balanced antibody response. To minimize the interference with the protein antigenic integrity, we further developed a systematic glycoconjugation strategy to conjugate this TLR7/8a1 onto the glycan chains of SARS-CoV-2 S1 glycoprotein via oxime ligation, in which S1 containing different numbers of aldehyde groups were obtained by differential periodate oxidation. The resulting TLR7/8a1-S1 conjugate triggered a potent humoral and cellular immunity in vivo. Together these data demonstrate the promise of these TLR7 and TLR7/8 agonists as effective built-in adjuvants, and the versatile oxime ligation strategy might broaden potential applications in designing different conjugate vaccines.
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A novel photoelectrochemical (PEC) sensor was developed for the ultra-sensitive and highly selective detection of hydroquinone (HQ), featuring a composite structure that combines 0D CdS nanoparticles with a 3D flower-like ZnIn2S4 microsphere. The sensor, termed rMIP/CdS/ZnIn2S4, employed molecularly imprinted polymers (MIPs) to achieve specific recognition of HQ. An p-phenylenediamine (pPD) polymer film was electrochemically polymerized onto the surface of the CdS/ZnIn2S4 composite-coated glassy carbon electrode (GCE). Through hydrogen bonding, HQ molecules were imprinted onto the polymer film. Subsequent elution removed these molecules, leaving behind specific recognition sites, enabling selective detection of HQ. The unique spatial structure and heterojunction properties of the 0D CdS nanoparticle/3D flower-like ZnIn2S4 composite, combined with molecular imprinting, significantly enhanced the photocurrent response and increased the selectivity and sensitivity for HQ detection. Under optimal conditions, the rMIP/CdS/ZnIn2S4 sensor demonstrated a low detection limit (0.7 nmol·L-1, S/N=3) over a wide linear range of 1-1200 nmol·L-1. The sensor was successfully applied to detect HQ in real water samples, showing promise for environmental pollution control applications.
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Pursuing high-performance conductive hydrogels is still hot topic in development of advanced flexible wearable devices. Herein, a tough, self-healing, adhesive double network (DN) conductive hydrogel (named as OSA-(Gelatin/PAM)-Ca, O-(G/P)-Ca) was prepared by bridging gelatin and polyacrylamide network with functionalized polysaccharide (oxidized sodium alginate, OSA) through Schiff base reaction. Thanks to the presence of multiple interactions (Schiff base bond, hydrogen bond, and metal coordination) within the network, the prepared hydrogel showed outstanding mechanical properties (tensile strain of 2800 % and stress of 630 kPa), high conductivity (0.72 S/m), repeatable adhesion performance and excellent self-healing ability (83.6 %/79.0 % of the original tensile strain/stress after self-healing). Moreover, the hydrogel-based sensor exhibited high strain sensitivity (GF = 3.66) and fast response time (<0.5 s), which can be used to monitor a wide range of human physiological signals. Based on this, excellent compression sensitivity (GF = 0.41 kPa-1 in the range of 90-120 kPa), a three-dimensional (3D) array of flexible sensor was designed to monitor the intensity of pressure and spatial force distribution. In addition, a gel-based wearable sensor was accurately classified and recognized ten types of gestures, achieving an accuracy rate of >96.33 % both before and after self-healing under three machine learning models (the decision tree, SVM, and KNN). This paper provides a simple method to prepare tough and self-healing conductive hydrogel as flexible multifunctional sensor devices for versatile applications in fields such as healthcare monitoring, human-computer interaction, and artificial intelligence.
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Multiple processes control quiescence of muscle stem cells (MuSCs), which is instrumental to guarantee long-term replenishment of the stem cell pool. Here, we describe that the G-proteins G12-G13 integrate signals from different G-protein-coupled receptors (GPCRs) to control MuSC quiescence via activation of RhoA. Comprehensive screening of GPCR ligands identified two MuSC-niche-derived factors, endothelin-3 (ET-3) and neurotensin (NT), which activate G12-G13 signaling in MuSCs. Stimulation with ET-3 or NT prevented MuSC activation, whereas pharmacological inhibition of ET-3 or NT attenuated MuSC quiescence. Inactivation of Gna12-Gna13 or Rhoa but not of Gnaq-Gna11 completely abrogated MuSC quiescence, which depleted the MuSC pool and was associated with accelerated sarcopenia during aging. Expression of constitutively active RhoA prevented exit from quiescence in Gna12-Gna13 mutant MuSCs, inhibiting cell cycle entry and differentiation via Rock and formins without affecting Rac1-dependent MuSC projections, a hallmark of quiescent MuSCs. The study uncovers a critical role of G12-G13 and RhoA signaling for active regulation of MuSC quiescence.
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A novel breakthrough has been achieved in gas detection through the innovative application of surface-enhanced Raman scattering (SERS) to hydrogen (H2) detection for the first time. This study capitalizes on the unique SERS effects of gold nanoparticles coupled with the redox interaction between hydrogen and crystal violet, allowing for the development of a magnetic SERS probe that demonstrated enhanced sensitivity and specificity. This new probe can detect hydrogen concentrations as low as 1% by volume in gaseous environments, offering a substantial improvement over the detection limits of traditional hydrogen alarms. Further, this report comprehensively detailed the synthesis of the FA-CV materials, instrumental analysis, and an in-depth evaluation of the SERS performance of the FA-CV substrate, underlining the outstanding sensitivity, stability, and recyclability of the probe. The introduction of SERS in this novel capacity not only contributes a valuable approach to gas sensing technologies, but also suggests promising avenues for the application of SERS in environmental monitoring and energy security. This illustrates the adaptability and potential impact of this powerful technique.
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The family Scolopacidae presents a valuable subject for evolutionary research; however, molecular studies of Scolopacidae are still relatively understudied, and the phylogenetic relationships of certain species remain unclear. In this study, we sequenced and obtained complete mitochondrial DNA (mtDNA) from Actitis hypoleucos and partial mtDNA from Numenius arquata, Limosa limosa, and Limnodromus semipalmatus. The complete mtDNA contained 13 protein-coding genes (PCGs), two ribosomal RNA genes, 22 tRNA genes, and a control region. Scolopacidae contained three types of start codons and five types of stop codons (including one incomplete stop codon, T--). In 13 protein-coding genes, average uncorrected pairwise distances (Aupd) revealed that ATP8 was the least conserved while COX3 had the lowest evolutionary rate. The ratio of Ka/Ks suggested that all PCGs were under purifying selection. Using two methods (maximum likelihood and Bayesian inference) to analyze the phylogenetic relationships of the family Scolopacidae, it was found that the genera Xenus and Actitis were clustered into another sister group, while the genus Phalaropus is more closely related to the genus Tringa. The genera Limnodromus, Gallinago, and Scolopax form a monophyletic group. This study improves our understanding of the evolutionary patterns and phylogenetic relationships of the family Scolopacidae.
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Polystyrene nanoparticles (PS NPs) released from plastic products have been demonstrated to pose a threat to leaf litter decomposition in streams. Given the multitrophic systems of species interactions, the effects of PS NPs through different exposure routes on ecosystem functioning remain unclear. Especially dietary exposure, a frequently overlooked pathway leading to toxicity, deserves more attention. A microcosm experiment was conducted in this study to assess the effects of waterborne and dietary exposure to PS NPs on the litter-based food chain involving leaves, microbial decomposers, and detritivores (river snails). Compared to waterborne contamination, dietary contamination resulted in lower microbial enzyme activities and a significantly higher decrease in the lipid content of leaves. For river snails, their antioxidant activity was significantly increased by 20.21%-69.93%, and their leaf consumption rate was significantly reduced by 16.60% through the dietary route due to the lower lipid content of leaves. Besides, the significantly decreased nutritional quality of river snails would negatively influence their palatability to predators. The findings of this study indicate that dietary exposure to PS NPs significantly impacts microbial and detritivore activities, thus affecting their functions in the detritus food chain as well as nutrient cycling.
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Cadena Alimentaria , Nanopartículas , Hojas de la Planta , Ríos , Caracoles , Contaminantes Químicos del Agua , Hojas de la Planta/química , Animales , Ríos/química , Contaminantes Químicos del Agua/análisis , Caracoles/efectos de los fármacos , Caracoles/fisiología , Poliestirenos , Plásticos , EcosistemaRESUMEN
Nanoplastics pose a potential threat to a wide variety of aquatic organisms. Despite the awareness of this existing hazard, the impact of nanoplastics on natural fungal communities remains a research gap. In this study, five dominant fungi species, isolated from a stream ecosystem, were used to explore the effects of different nano-polystyrene (nano-PS) particles concentrations on a simulated fungal community. Specifically, the evaluation was conducted regarding the fungal growth, reproductivity, structural composition, and ecological function in leaf litter decomposition. A 15-day exposure experiment showed that 100 µg/L nano-PS significantly reduced the microcosm pH. The extracellular enzyme activities of ß-glucosidase, leucine-aminopeptidase, and peroxidase were significantly promoted by nano-PS exposure for 5 days or 15 days. Total sporulation rate significantly decreased after the 15-day exposure to 1 and 100 µg/L nano-PS and significantly increased under 10 µg/L nano-PS. In contrast, nano-PS concentrations had no effects on fungal biomass. In addition, the reduced relative abundance of Geotrichum candidum lowered its contribution to leaf decomposition, resulting in a decreased litter decomposition rate of a 24.5-27.9 % after exposure. This suggests that 1-100 µg/L nano-PS inhibited leaf decomposition by inhibiting fungal reproduction and reducing the contribution of specific fungal species. In addition, the findings highlight the importance of exploring the potential mechanisms of the interaction between nanoplastics and fungal species.
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Hongos , Hojas de la Planta , Contaminantes Químicos del Agua , Hongos/efectos de los fármacos , Hongos/fisiología , Contaminantes Químicos del Agua/toxicidad , Micobioma/efectos de los fármacos , Nanopartículas/toxicidad , Biodegradación Ambiental , Ecosistema , PoliestirenosRESUMEN
BACKGROUND: Radiomics has been used in the diagnosis of tumor lymph node metastasis (LNM). However, to date, most studies have been based on intratumoral radiomics. Few studies have focused on the use of 18F-fluorodeoxyglucose positron emission computed tomography (18F-FDG PET/CT) peritumoral radiomics for the diagnosis of LNM in colorectal cancer (CRC). PURPOSE: Determining the value of radiomics features extracted from 18F-FDG PET/CT images of the peritumoral region in predicting LNM in patients with CRC. METHODS: The clinical data and preoperative 18F-FDG PET/CT images of 244 CRC patients were retrospectively analyzed. Intratumoral and peritumoral radiomics features were screened using the mutual information method, and least absolute shrinkage and selection operator regression. Based on the selected radiomics features, a radiomics score (Rad-score) was calculated, and independent risk factors obtained from univariate and multivariate logistic regression analyses were used to construct clinical and combined (Radiomics + Clinical) models. The performance of these models was evaluated using the DeLong test, while their clinical utility was assessed by decision curve analysis. Finally, a nomogram was constructed to visualize the predictive model. RESULTS: The most optimal set of features retained by the feature filtering process were all peritumoral radiomic features. Carcinoembryonic antigen levels, PET/CT-reported lymph node status and Rad-score were found to be independent risk factors for LNM. All three LNM risk assessment models exhibited good predictive performance, with the combined model showing the best classification results, with areas under the curve of 0.85 and 0.76 in the training and validation groups, respectively. The DeLong test revealed that the performance of the combined model was superior to that of the clinical and radiomics models in both the training and validation groups, although this difference was only statistically significant in the training group. DCA indicated that the combined model displayed better clinical utility. CONCLUSIONS: 18F-FDG PET/CT peritumoral radiomics is uniquely suited to predict the presence of LNM in patients with CRC. In particular, the predictive efficacy of LNM for precision therapy and individualized patient management can be improved by using a combination of clinical risk factors.
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Neoplasias Colorrectales , Fluorodesoxiglucosa F18 , Metástasis Linfática , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Neoplasias Colorrectales/diagnóstico por imagen , Neoplasias Colorrectales/patología , Masculino , Metástasis Linfática/diagnóstico por imagen , Femenino , Persona de Mediana Edad , Anciano , Periodo Preoperatorio , Procesamiento de Imagen Asistido por Computador/métodos , Estudios Retrospectivos , Adulto , Anciano de 80 o más Años , RadiómicaRESUMEN
Pregnancy heightens susceptibility to influenza A virus (IAV) infection, thereby increasing the risk of severe pneumonia and maternal mortality. It also raises the chances of adverse outcomes in offspring, such as fetal growth restriction, preterm birth, miscarriage, and stillbirth in offsprings. However, the underlying mechanisms behind these effects remain largely unknown. Syncytiotrophoblast cells, crucial in forming the placental barrier, nutrient exchange and hormone secretion, have not been extensively studied for their responses to IAV. In our experiment, we used Forskolin-treated BeWo cells to mimic syncytiotrophoblast cells in vitro, and infected them with H1N1, H5N1 and H7N9 virus stains. Our results showed that syncytiotrophoblast cells, with their higher intensity of sialic acid receptors, strongly support IAV infection and replication. Notably, high-dose viral infection and prolonged exposure resulted in a significant decrease in fusion index, as well as gene and protein expression levels associated with trophoblast differentiation, ß-human chorionic gonadotropin secretion, estrogen and progesterone biosynthesis, and nutrient transport. In pregnant BALB/c mice infected with the H1N1 virus, we observed significant decreases in trophoblast differentiation and hormone secretion gene expression levels. IAV infection also resulted in preterm labor, fetal growth restriction, and increased maternal and fetal morbidity and mortality. Our findings indicate that IAV infection in syncytiotrophoblastic cells can result in adverse pregnancy outcomes by altering trophoblast differentiation, suppressing of ß-hCG secretion, and disrupting placental barrier function.
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Subtipo H1N1 del Virus de la Influenza A , Ratones Endogámicos BALB C , Infecciones por Orthomyxoviridae , Resultado del Embarazo , Trofoblastos , Femenino , Trofoblastos/virología , Embarazo , Animales , Humanos , Subtipo H1N1 del Virus de la Influenza A/fisiología , Ratones , Infecciones por Orthomyxoviridae/virología , Gripe Humana/virología , Línea Celular , Subtipo H5N1 del Virus de la Influenza A/fisiología , Subtipo H7N9 del Virus de la Influenza A/fisiología , Subtipo H7N9 del Virus de la Influenza A/patogenicidad , Complicaciones Infecciosas del Embarazo/virología , Placenta/virología , Replicación ViralRESUMEN
BACKGROUND: Subarachnoid hemorrhage (SAH) represents a form of cerebrovascular event characterized by a notable mortality and morbidity rate. Fibroblast growth factor 21 (FGF21), a versatile hormone predominantly synthesized by the hepatic tissue, has emerged as a promising neuroprotective agent. Nevertheless, the precise impacts and underlying mechanisms of FGF21 in the context of SAH remain enigmatic. METHODS: To elucidate the role of FGF21 in inhibiting the microglial cGAS-STING pathway and providing protection against SAH-induced cerebral injury, a series of cellular and molecular techniques, including western blot analysis, real-time polymerase chain reaction, immunohistochemistry, RNA sequencing, and behavioral assays, were employed. RESULTS: Administration of recombinant fibroblast growth factor 21 (rFGF21) effectively mitigated neural apoptosis, improved cerebral edema, and attenuated neurological impairments post-SAH. Transcriptomic analysis revealed that SAH triggered the upregulation of numerous genes linked to innate immunity, particularly those involved in the type I interferon (IFN-I) pathway and microglial function, which were notably suppressed upon adjunctive rFGF21 treatment. Mechanistically, rFGF21 intervention facilitated mitophagy in an AMP-activated protein kinase (AMPK)-dependent manner, thereby preventing mitochondrial DNA (mtDNA) release into the cytoplasm and dampening the activation of the DNA-sensing cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway. Conditional knockout of STING in microglia markedly ameliorated the inflammatory response and mitigated secondary brain injuries post-SAH. CONCLUSION: Our results present the initial evidence that FGF21 confers a protective effect against neuroinflammation-associated brain damage subsequent to SAH. Mechanistically, we have elucidated a novel pathway by which FGF21 exerts this neuroprotection through inhibition of the cGAS-STING signaling cascade.
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Factores de Crecimiento de Fibroblastos , Proteínas de la Membrana , Ratones Endogámicos C57BL , Mitofagia , Enfermedades Neuroinflamatorias , Nucleotidiltransferasas , Transducción de Señal , Hemorragia Subaracnoidea , Animales , Proteínas de la Membrana/metabolismo , Factores de Crecimiento de Fibroblastos/metabolismo , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/metabolismo , Hemorragia Subaracnoidea/patología , Enfermedades Neuroinflamatorias/metabolismo , Enfermedades Neuroinflamatorias/etiología , Mitofagia/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Nucleotidiltransferasas/metabolismo , Masculino , Ratones , ADN Mitocondrial/genética , ADN Mitocondrial/metabolismo , Microglía/metabolismo , Microglía/patología , Microglía/efectos de los fármacos , Apoptosis/efectos de los fármacosRESUMEN
The emergence of drug-resistant Enterobacteriaceae carrying plasmid-mediated ß-lactamase genes has become a significant threat to public health. Organisms in the Enterobacteriaceae family containing New Delhi metallo-ß-lactamase1 (NDM-1) and its variants, which are capable of hydrolyzing nearly all ß-lactam antibacterial agents, including carbapenems, are referred to as superbugs and distributed worldwide. Despite efforts over the past decade, the discovery of an NDM-1 inhibitor that can reach the clinic remains a challenge. Here, we identified oxidized glutathione (GSSG) as a metabolic biomarker for blaNDM-1 using a non-targeted metabolomics approach and demonstrated that GSSG supplementation could restore carbapenem susceptibility in Escherichia coli carrying blaNDM-1 in vitro and in vivo. We showed that exogenous GSSG promotes the bactericidal effects of carbapenems by interfering with intracellular redox homeostasis and inhibiting the expression of NDM-1 in drug-resistant E. coli. This study establishes a metabolomics-based strategy to potentiate metabolism-dependent antibiotic efficacy for the treatment of antibiotic-resistant bacteria.
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Antibacterianos , Carbapenémicos , Escherichia coli , Glutatión , beta-Lactamasas , Animales , Humanos , Ratones , Antibacterianos/farmacología , beta-Lactamasas/metabolismo , beta-Lactamasas/genética , Carbapenémicos/farmacología , Escherichia coli/genética , Escherichia coli/efectos de los fármacos , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/microbiología , Glutatión/metabolismo , Metabolómica , Pruebas de Sensibilidad Microbiana , Oxidación-Reducción/efectos de los fármacos , Farmacorresistencia BacterianaRESUMEN
Background: Magnesium sulfate, an intravenous adjuvant, has recently attracted immense attention in multimodal analgesia. Previous studies confirmed the crucial role of magnesium sulfate in postoperative pain and nociceptive hypersensitivity. However, the effect of magnesium sulfate in multimodal analgesia on the quality of recovery (QoR) for elderly patients has not been thoroughly studied. Therefore, the present experiment aimed to investigate the effect of continuous intravenous magnesium sulfate on the quality of postoperative recovery in elderly patients undergoing total knee arthroplasty (TKA). Patients and Methods: In this study, a total of 148 patients scheduled to undergo unilateral total knee arthroplasty were randomized into a magnesium sulfate group (Group M, n=68) and a control group (Group C, n=66) using a double-blind, randomized controlled trial. Before induction of anesthesia, Group M received intravenous magnesium sulfate (40 mg/kg) for 15 min, followed by a continuous infusion (15 mg/kg) until the end of the procedure. In the same manner, Group C received an infusion of the same amount of isotonic saline using the same method as the Group M. Results: Compared with Group C, Group M had significantly better QoR-15 scores on postoperative day 1(POD1) than Group C (P <0.05). Analysis of the dimensions of QoR-15 scores indicated that Group M exhibited notably reduced levels of pain, and higher levels of emotional state and physical comfort than Group C (P <0.05). Furthermore, Group C had significantly higher numerical rating scale (NRS) scores at POD1 than Group M (P <0.05). Conclusion: For elderly patients undergoing knee arthroplasty, magnesium sulfate can be used as an adjuvant in a multimodal analgesic regimen to reduce early postoperative pain and improve the quality of early postoperative recovery.
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Artroplastia de Reemplazo de Rodilla , Sulfato de Magnesio , Humanos , Anciano , Sulfato de Magnesio/uso terapéutico , Estudios Prospectivos , Analgésicos , Dolor Postoperatorio/tratamiento farmacológico , Método Doble Ciego , Analgésicos OpioidesRESUMEN
Background: Patients undergoing intestinal tumour surgery are fasted preoperatively for a series of bowel preparations, which makes it difficult to assess the patients' volume, posing a challenge to intraoperative fluid replacement. Besides, inappropriate fluid therapy can cause organ damage and affect the prognosis of patients, and it increases the burden of patients and has a certain impact on patients and families. Material and methods: The authors designed a single-centre, prospective, single-blinded, randomized, parallel-controlled trial. Fifty-four patients undergoing elective radical resection of colorectal cancer were selected and divided into two groups according to whether transesophageal echocardiography (TEE) was used or not during the operation, that is the goal-directed fluid therapy (GDFT) group (group T) guided by TEE and the restrictive fluid therapy group (group C). Fluid replacement was guided according to left ventricular end-diastolic volume index (LVEDVI) in group T and according to restrictive fluid replacement regimen in group C. Results: The first postoperative exhaust time and defecation time in group T [(45±21), (53±24) h] were significantly shorter (P<0.05) than those in group C [(63±26), (77±30) h]. There were no significant differences (P>0.05) in liquid intake time and postoperative nausea and vomiting incidences between the two groups. The total intraoperative fluid volume in group T was significantly higher (P<0.05) than that in group C. There was no significant difference (P>0.05) in urine volume between the two groups. There were no significant differences (P>0.05) in lactate content, mean arterial pressure, and heart rate at various time points between the two groups. The length of hospital stay in group C [(18±4) days] was significantly longer (P<0.05) than that in group T [(15±4) days]. Conclusions: For patients undergoing colorectal cancer surgery, fluid therapy by monitoring LVEDVI resulted in faster recovery of gastrointestinal function and shorter hospital stay.
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The landscape pattern determines water pollution source and sink processes and plays an important role in regulating river water quality. Due to scale effects, studies on the relationship between landscape pattern and river water quality showed variance at different scales. However, there is still a lack of integrated study on the scale effect of landscape pattern and river water quality dynamics. This study collected 4 041 data from results of previous publications to address the characteristics of landscape pattern and river water quality dynamics at different scales and to identify the key temporal and spatial scales as well as landscape pattern indices for regulating river water quality. The results indicated that, compared to precipitation events, base flow periods, and interannual scales, the high-flow period was the key temporal scale for linking landscape pattern on river water quality. Compared to the watershed scale, the landscape pattern of buffer zones had a greater impact on river water quality. The high-flow period-buffer zone scale was the key spatiotemporal coupling scale for linking landscape pattern and river water quality. Compared to croplands, water bodies, grasslands, and the overall landscape of the watershed, the landscape pattern of forests and urban areas had a greater impact on river water quality. Fragmentation degree was the most important landscape pattern factor regulating river water quality. In river water quality management, it is important to focus on the landscape configuration of buffer zones, increase forest area, reduce patch density of forests and water bodies, and decrease the aggregation degree of urban areas.
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This study evaluated a synergetic waste activated sludge treatment strategy with environmentally friendly zero-valent iron nanoparticles (Fe0) and peroxysulfate. To verify the feasibility of the synergistic treatment, Fe0, peroxysulfate, and the mixture of peroxysulfate and Fe0 (synergy treatment) were added to different sludge fermentation systems. The study demonstrated that the synergy treatment fermentation system displayed remarkable hydrolysis performance with 435.50 mg COD/L of protein and 197.67 mg COD/L of polysaccharide, which increased 1.13-2.85 times (protein) and 1.12-1.49 times (polysaccharide) for other three fermentation system. Additionally, the synergy treatment fermentation system (754.52 mg COD/L) exhibited a well acidification performance which was 1.35-41.73 times for other systems (18.08-557.27 mg COD/L). The synergy treatment fermentation system had a facilitating effect on the activity of protease, dehydrogenase, and alkaline phosphatase, which guaranteed the transformation of organic matter. Results also indicated that Comamonas, Soehngenia, Pseudomonas, and Fusibacter were enriched in synergy treatment, which was beneficial to produce SCFAs. The activation of Fe0 on peroxysulfate promoting electron transfer, improving the active groups, and increasing the enrichment of functional microorganisms showed the advanced nature of synergy treatment. These results proved the feasibility of synergy treatment with Fe0 and peroxysulfate to enhance waste activated sludge anaerobic fermentation.
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Microbiota , Aguas del Alcantarillado , Fermentación , Anaerobiosis , Ácidos Grasos Volátiles/metabolismo , Hierro/farmacología , Polisacáridos , Concentración de Iones de HidrógenoRESUMEN
A universal platform is developed for dropletizing single cell plate-based multiomic assays, consisting of three main pillars: a miniaturized open Heterogeneous Hydrogel reactor (abbreviated HetHydrogel) for multi-step biochemistry, its tunable permeability that allows Tn5 tagmentation, and single cell droplet barcoding. Through optimizing the HetHydrogel manufacturing procedure, the chemical composition, and cell permeation conditions, simultaneous high-throughput mitochondrial DNA genotyping and chromatin profiling at the single-cell level are demonstrated using a mixed-species experiment. This platform offers a powerful way to investigate the genotype-phenotype relationships of various mtDNA mutations in biological processes. The HetHydrogel platform is believed to have the potential to democratize droplet technologies, upgrading a whole range of plate-based single cell assays to high throughput format.
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ADN Mitocondrial , Hidrogeles , Análisis de la Célula Individual , Hidrogeles/química , ADN Mitocondrial/genética , Humanos , Animales , Mutación , MultiómicaRESUMEN
Endogenous partial denitrification (EPD) has drawn a lot of interest due to its abundant nitrite (NO2--N) accumulation capacity. However, the poor phosphate (PO43--P) removal rate of EPD restricts its promotion and application. In this study, the potentiality of various nano zero-valent iron (nZVI) concentrations (0, 20, 40, and 80 mg/L) on NO2--N accumulation and PO43--P removal in EPD systems had been investigated. Results showed that nZVI improved NO2--N accumulation and PO43--P removal, with the greatest nitrate-to-nitrite transformation ratio (NTR) and PO43--P removal rate of 97.74 % and 64.76 % respectively at the optimum nZVI level (80 mg/L). Microbial community analysis also proved that nZVI had a remarkable influence on the microbial community of EPD. Candidatus_Competibacter was contribute to NO2--N accumulation which was enriched from 24.74 % to 40.02 %. The enrichment of Thauera, Rhodobacteraceae, Pseudomonas were contributed to PO43--P removal. The chemistry of nZVI not only compensated for the deficiency of biological PO43--P removal, but also enhanced NO2--N enrichment. Therefore, nZVI had the huge potentiality to improve the operational performance of the EPD system.
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Nitratos , Nitritos , Fósforo , Hierro , Desnitrificación , Dióxido de Nitrógeno , Nitrógeno , Aguas del Alcantarillado , Reactores BiológicosRESUMEN
Programmable genome insertion (or knock-in) is vital for both fundamental and translational research. The continuously expanding number of CRISPR-based genome insertion strategies demonstrates the ongoing development in this field. Common methods for site-specific genome insertion rely on cellular double-strand breaks repair pathways, such as homology-directed repair, non-homologous end-joining, and microhomology-mediated end joining. Recent advancements have further expanded the toolbox of programmable genome insertion techniques, including prime editing, integrase coupled with programmable nuclease, and CRISPR-associated transposon. These tools possess their own capabilities and limitations, promoting tremendous efforts to enhance editing efficiency, broaden targeting scope and improve editing specificity. In this review, we first summarize recent advances in programmable genome insertion techniques. We then elaborate on the cons and pros of each technique to assist researchers in making informed choices when using these tools. Finally, we identify opportunities for future improvements and applications in basic research and therapeutics.
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Antimony (Sb) biomethylation is an important but uninformed process in Sb biogeochemical cycling. Methylated Sb species have been widely detected in the environment, but the gene and enzyme for Sb methylation remain unknown. Here, we found that arsenite S-adenosylmethionine methyltransferase (ArsM) is able to catalyze Sb(III) methylation. The stepwise methylation by ArsM forms mono-, di-, and trimethylated Sb species. Sb(III) is readily coordinated with glutathione, forming the preferred ArsM substrate which is anchored on three conserved cysteines. Overexpressing arsM in Escherichia coli AW3110 conferred resistance to Sb(III) by converting intracellular Sb(III) into gaseous methylated species, serving as a detoxification process. Methylated Sb species were detected in paddy soil cultures, and phylogenetic analysis of ArsM showed its great diversity in ecosystems, suggesting a high metabolic potential for Sb(III) methylation in the environment. This study shows an undiscovered microbial process methylating aqueous Sb(III) into the gaseous phase, mobilizing Sb on a regional and even global scale as a re-emerging contaminant.