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Microbial ammonia oxidation is the initial nitrification step used in biological nitrogen-removal during water treatment processes, and the discovery of complete ammonia-oxidizing (comammox) bacteria added a novel member to this functional group. It is important to identify and understand the predominant microorganisms responsible for ammonium removal in biotechnological process design and optimization. In this study, we used a full-scale bioreactor to treat ammonium in groundwater (9.3 ± 0.5 mg NH4+-N/L) and investigated the key ammonia-oxidizing prokaryotes present. The groundwater ammonium was stably and efficiently oxidized throughout ∼700 days of bioreactor operation. 16S rRNA gene amplicon sequencing of the bioreactor community showed a high abundance of Nitrospira (12.5-45.9%), with the dominant sequence variant (3.5-37.8%) most closely related to Candidatus Nitrospira nitrosa. Furthermore, analyses of amoA, the marker gene for ammonia oxidation, indicated the presence of two distinct comammox Nitrospira populations, however, the relative abundance of only one of these populations was strongly correlated to ammonia oxidation rates and was robustly expressed. After 380 days of operation copper wires were immersed into the reactor at 0.04-0.06 m2/m3 tank, which caused a gradual abundance increase of one discrete comammox Nitrospira population. However, further increase of the copper dosing (0.08 m2/m3 tank) inverted the most abundant ammonia-oxidizing population to Nitrosomonas sp. These results indicate that comammox Nitrospira were capable of efficient ammonium removal in groundwater without exogenous nutrients, but copper addition can stimulate comammox Nitrospira or lead to dominance of Nitrosomonas depending on dosage.In this study, a suite of natural wastewater sources is tested to understand the effects of wastewater composition and source on electrochemically driven nitrogen and phosphorus nutrient removal. Kinetics, electrode behavior, and removal efficiency were evaluated during electrochemical precipitation, whereby a sacrificial magnesium (Mg) anode was used to drive precipitation of ammonium and phosphate. The electrochemical reactor demonstrated fast kinetics in the natural wastewater matrices, removing up to 54% of the phosphate present in natural wastewater within 1 min, with an energy input of only 0.04 kWh.m-3. After 1 min, phosphate removal followed a zero-order rate law in the 1 min - 30 min range. The zero-order rate constant (k) appears to depend upon differences in wastewater composition, where a faster rate constant is associated with higher Cl- and NH4+ concentrations, lower Ca2+ concentrations, and higher organic carbon content. The sacrificial Mg anode showed the lowest corrosion resistance in the natources enables fast kinetics for phosphate removal at low energy input.The utilization of natural ores and/or mine waste as substrate in constructed wetlands (CWs) to enhance nutrient removal performance has been gaining high popularity recently. However, the knowledge regarding the long-term feasibility and key removal mechanisms, particularly the potential negative environmental effects of contaminants leached from mine waste is far insufficient. This study, for the first time, performed a critical assessment by using different CWs with three mine waste (coal gangue, iron ore and manganese ore) as substrates in a 385-day experiment treating wastewater with varying nutrient loadings. The results showed that the addition of mine waste in CWs increased removal of total phosphorus (TP) by 17-34%, and total nitrogen (TN) by 11-51%. The higher removal of TP is mainly attributed to the strong binding mechanism of phosphate with the oxides and hydroxides of Mn, Fe and/or Al, which are leached out of mine waste. Moreover, integration of mine waste in CWs also significantly stimulated biofilm establishment and enriched the relative abundance of key functional genes related to the nitrogen cycle, supporting the observed high-rate nitrogen removal. However, leaching of heavy metals (Fe, Mn, Cu and Cr) from the beded mine waste in the experimented CWs was monitored, which further influenced cytoplasmic enzymes and created oxidative stress damage to plants, resulting in a decline of nutrient uptake by plants.Bacillus subtilis immobilization in calcium alginate microparticles was investigated using two techniques droplet microfluidics-based in T-junction geometry composed with a double droplet generation system and conventional dripping system. Ro 61-8048 Alginate microparticles produced by microfluidic technology presented an average size of 68.35 µm with low polydispersity and immobilization efficiency around 86%. The cell response was evaluated in batch cultivation for 24 h, viewing lipase production compared to free cells. In this study, the batch cultivation with immobilized cells in alginate microparticles presented lipase production about 2.4 and 1.7 times higher than cultivation with cells immobilized cells by conventional technique and free cells cultivations. According to the results, this main novelty of the double T junction technique is an innovative contribution as a tool for cell immobilization on a laboratory scale, since the cultivation of immobilized cells in microparticles of small size and low polydispersity favors cell growth and increases the productivity of important metabolites of industrial biotechnology.Candida kefyr (Kluyveromyces marxianus), an ascomycetous environmental yeast, occasionally isolated from dairy products, represents an uncommon but emerging pathogen in immunocompromised patients. Herein, we present a case of C. kefyr pyelonephritis in a 41-year-old, previously immunocompetent, patient who was hospitalized in an COVID-19 ICU. Pyelonephritis was associated with caliectasis and obstruction due to possible fungus ball formation. Predisposing factors included ICU stay, use of broad spectrum antibiotics and steroids, central venous catheterization, mechanical ventilation and urologic manipulation. Susceptibility testing revealed high MIC values to amphotericin B. Infection was effectively controlled by prolonged administration of fluconazole without further surgical intervention. COVID-19 complicated with invasive candidiasis is an increasingly observed clinical situation that warrants high suspicion index and careful evaluation of laboratory data.Multiple myeloma is currently incurable, and the incidence rate is increasing year by year worldwide. Although in recent years the combined treatment plan based on proteasome inhibitors and immunomodulatory drugs has greatly improved the treatment effect of multiple myeloma, most patients still relapse and become resistant to current treatments. To solve this problem, scientists are committed to developing drugs with higher specificity, such as iberdomide, which is highly specific to ikaros and aiolos. This review aims to focus on the small molecular agents that are being researched/clinically used for the treatment of multiple myeloma, including the target mechanism, structure-activity relationship and application prospects of small molecular agents.Antibody-drug conjugates (ADCs) are targeted therapies, mainly used in oncology, consisting in a three-component molecular architecture combining a highly potent drug conjugated via a linker onto a monoclonal antibody (mAb), designed for the selective delivery of the drug to the tumor site. The linker is a key component, defining the ADC stability and mechanism of action, and particularly the drug release strategy. In this study, we have developed and synthesized a cleavable linker, which possesses an Asn-Pro-Val (NPV) sequence sensitive to the human neutrophil elastase (HNE), overexpressed in the tumor microenvironment. This linker permitted the site-specific conjugation of the cell-permeable drug, monomethyl auristatin E (MMAE), onto trastuzumab, using a disulfide re-bridging technology. The resulting ADC was then evaluated in vitro. This conjugate demonstrated retained antigen (Ag) binding affinity and exhibited high subnanomolar potency against Ag-positive tumor cells after internalization, suggesting an intracellular mechanism of linker cleavage. While no internalization and cytotoxic activity of this ADC was observed on Ag-negative cells in classical conditions, the supplementation of exogenous HNE permitted to restore a nanomolar activity on these cells, suggesting an extracellular mechanism of drug release in these conditions. This in vitro proof of concept tends to prove that the NPV sequence could allow a dual intra- and extracellular mechanism of drug release. This work represents a first step in the design of original ADCs with a new dual intra- and extracellular drug delivery system and opens the way to further experimentations to evaluate their full potential in vivo.

While cumulative loading of the pelvic floor during exercise appears to increase the risk of developing pelvic floor disorders, the pathophysiologic role of pelvic floor loading is poorly understood. link2 The aim of this exploratory study was to present a method for evaluating vibrational frequency damping of the female pelvic floor and to investigate the potential utility of this approach in a preliminary evaluation.

Female participants were instrumented with an intravaginal accelerometer and a hip-mounted accelerometer, then ran on a treadmill at 7km/h and 10km/h both before and after a 30-min self-selected pace. Displacement of the pelvic floor relative to the bony pelvis was calculated using double integration of the accelerometer data. Vibrational damping coefficients were calculated using a wavelet-based approach to determine the effect of continence status, parity, running speed and time on vibrational damping.

Seventeen women (n=10 reported regularly leaking urine while exercising, while n=7 reported not leaking) completed the running protocol. link3 No differences in vibrational damping were detected between continent and incontinent women when all frequency bands were evaluated together, however significant effects of parity, time, running speed and continence status were found within specific frequency bands. Parous women demonstrated less damping in the 25-40Hz band compared to nulliparae, damping in the 13-16Hz band was lower after the 30-min run, and incontinent women demonstrated lower damping in the 4.5-5.5Hz band than continent women when running at 7km/h.

Intra-vaginal vibrational damping may be useful in detecting biomechanical mechanisms associated with pelvic floor disorders experienced by females during exercise.

Intra-vaginal vibrational damping may be useful in detecting biomechanical mechanisms associated with pelvic floor disorders experienced by females during exercise.Replication-incompetent adenovirus (Ad) vectors have been widely used as gene delivery vehicles in both gene therapy studies and basic studies for gene function analysis due to their highly advantageous properties, which include high transduction efficiencies, relatively large capacities for transgenes, and high titer production. In addition, Ad vectors induce moderate levels of innate immunity and have relatively high thermostability, making them very attractive as potential vaccine vectors. Accordingly, it is anticipated that Ad vectors will be used in vaccines for the prevention of infectious diseases, including Ebola virus disease and acquired immune deficiency syndrome (AIDS). Much attention is currently focused on the potential use of an Ad vector vaccine for coronavirus disease 2019 (COVID-19). In this review, we describe the basic properties of an Ad vector, Ad vector-induced innate immunity and immune responses to Ad vector-produced transgene products. Development of novel Ad vectors which can overcome the drawbacks of conventional Ad vector vaccines and clinical application of Ad vector vaccines to several infectious diseases are also discussed.

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