The recent success of immunotherapies has highlighted the power of leveraging the immune system in the fight against cancer. In order for most immune‐based therapies to succeed, T cell subsets with ...the correct tumor‐targeting specificities must be mobilized. When such specificities are lacking, providing the immune system with tumor antigen material for processing and presentation is a common strategy for stimulating antigen‐specific T cell populations. While straightforward in principle, experience has shown that manipulation of the antigen presentation process can be incredibly complex, necessitating sophisticated strategies that are difficult to translate. Herein, the design of a biomimetic nanoparticle platform is reported that can be used to directly stimulate T cells without the need for professional antigen‐presenting cells. The nanoparticles are fabricated using a cell membrane coating derived from cancer cells engineered to express a co‐stimulatory marker. Combined with the peptide epitopes naturally presented on the membrane surface, the final formulation contains the necessary signals to promote tumor antigen‐specific immune responses, priming T cells that can be used to control tumor growth. The reported approach represents an emerging strategy that can be used to develop multiantigenic, personalized cancer immunotherapies.
Cancer cells are genetically engineered to express a co‐stimulatory marker that enables them to directly present their own antigens under an immunostimulatory context. Cell‐membrane‐coated nanoparticles sourced from these modified cells elicit antitumor immunity in vivo while bypassing the need for traditional cell‐mediated antigen presentation. This approach may ultimately enable the facile design of personalized artificial antigen presentation platforms.
Stretchable and conductive hydrogels have been intensively studied as wearable electronics to monitor the physiological activities of human bodies. However, it remains a challenge to fabricate robust ...hydrogels as sensors with complex 3D structures. Here, we designed a 3D printable ink from cellulose nanocrystals (CNCs), deep eutectic solvents (DESs), and ionically cross-linked polyacrylic acid (PAA). DESs composed of choline chloride and ethylene glycol served as a nonvolatile medium with high ionic conductivity. The dispersion of CNCs in a mixture of DESs, acrylic acid, and Al3+ ions formed ionogels with a reversible physical network for 3D printing. After the printing process, the ionogel was solidified by the photopolymerization of acrylic acid in the presence of Al3+ ions to form a second ionically cross-linked network. The first physical network of CNCs provides an energy-dissipating mechanism to make a strong and highly stretchable nanocomposite ionogel. When compared to hydrogels, we found that the DES/CNC nanocomposite ionogel was more stable in the air because of the low volatility of DESs. We further used the DES/CNC ink to 3D print an auxetic sensor with negative Poisson’s ratios so that the sensor provided a conformal contact with the skin during large deformation. In addition, the auxetic sensor could continuously monitor and identify different motions of the human body by the change in resistance. These results demonstrate a simple and rapid strategy to fabricate stable and sensitive strain sensors from cheap and renewable feedstock.
•Nitrate bio-reduction was achieved in membrane biofilm reactors using propane or butane as electron donors.•Limited oxygen was an important triggering factor for propane/butane-driven nitrate ...reduction.•Propane/butane oxidizers (Mycobacterium/Rhodococcus/Thauera) and denitrifiers were enriched.
Nitrate contamination has been commonly detected in water environments and poses serious hazards to human health. Previously methane was proposed as a promising electron donor to remove nitrate from contaminated water. Compared with pure methane, natural gas, which not only contains methane but also other short chain gaseous alkanes (SCGAs), is less expensive and more widely available, representing a more attractive electron source for removing oxidized contaminants. However, it remains unknown if these SCGAs can be utilized as electron donors for nitrate reduction. Here, two lab-scale membrane biofilm reactors (MBfRs) separately supplied with propane and butane were operated under oxygen-limiting conditions to test its feasibility of microbial nitrate reduction. Long-term performance suggested nitrate could be continuously removed at a rate of ∼40–50 mg N/L/d using propane/butane as electron donors. In the absence of propane/butane, nitrate removal rates significantly decreased both in the long-term operation (∼2–10 and ∼4–9 mg N/L/d for propane- and butane-based MBfRs, respectively) and batch tests, indicating nitrate bio-reduction was driven by propane/butane. The consumption rates of nitrate and propane/butane dramatically decreased under anaerobic conditions, but recovered after resupplying limited oxygen, suggesting oxygen was an essential triggering factor for propane/butane-based nitrate reduction. High-throughput sequencing targeting 16S rRNA, bmoX and narG genes indicated Mycobacterium/Rhodococcus/Thauera were the potential microorganisms oxidizing propane/butane, while various denitrifiers (e.g. Dechloromonas, Denitratisoma, Zoogloea, Acidovorax, Variovorax, Pseudogulbenkiania and Rhodanobacter) might perform nitrate reduction in the biofilms. Our findings provide evidence to link SCGA oxidation with nitrate reduction under oxygen-limiting conditions and may ultimately facilitate the design of cost-effective techniques for ex-situ groundwater remediation using natural gas.
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Anticancer vaccines train the body's own immune system to recognize and eliminate malignant cells based on differential antigen expression. While conceptually attractive, clinical efficacy is lacking ...given several key challenges stemming from the similarities between cancerous and healthy tissue. Ideally, an effective vaccine formulation would deliver multiple tumor antigens in a fashion that potently stimulates endogenous immune responses against those antigens. Here, it is reported on the fabrication of a biomimetic, nanoparticulate anticancer vaccine that is capable of delivering autologously derived tumor antigen material together with a highly immunostimulatory adjuvant. The two major components, tumor antigens and adjuvant, are presented concurrently in a fashion that maximizes their ability to promote effective antigen presentation and activation of downstream immune processes. Ultimately, it is demonstrated that the formulation can elicit potent antitumor immune responses in vivo. When combined with additional immunotherapies such as checkpoint blockades, the nanovaccine demonstrates substantial therapeutic effect. Overall, the work represents the rational application of nanotechnology for immunoengineering and can provide a blueprint for the future development of personalized, autologous anticancer vaccines with broad applicability.
A biomimetic, nanoparticulate anticancer vaccine is fabricated by coating membrane derived from cancer cells onto an immunostimulatory core. The resulting nanoformulation can promote immunity against multiple tumor antigens. When the nanovaccine is combined with checkpoint blockade therapy, significant control of tumor growth is achieved. This approach may ultimately be adapted toward designing potent autologous vaccines made from patient‐derived tumor material.
The current study aims to investigate the neurodevelopment of premature infants after intravitreal injections of bevacizumab (IVB) for the treatment of retinopathy of prematurity (ROP) up to the age ...of 2 years.
The study design was retrospective observational case series conducted at an institutional referral center. Infants with type 1 ROP were classified into 3 groups: laser only, IVB only, and a combination of IVB and laser treatment. Main Outcome Measures were neurodevelopmental outcomes of the patients after treatment were assessed by Bayley Scales for Infant Development.
Sixty-one patients who finished the neurodevelopmental survey were included. No detrimental effects on neurodevelopment were found in IVB group compared with the patients who received laser treatment only. The patients in the IVB + laser group had a higher incidence of significant mental (p = 0.028) and psychomotor (p = 0.002) impairment at 24 months than the patients in the laser group. The odds ratio of having severe psychomotor defects in the IVB + laser group was 5.3 compared with the laser group (p = 0.041). The causal source for the differences that were detected remained unknown due to lack of randomization in the study and accompanying bias in patient selection.
Two years after laser and/or intravitreal injections of bevacizumab for infants with retinopathy of prematurity, no difference on neurodevelopment for those who received only bevacizumab versus only laser treatment were found. Those infants who required rescue therapy with laser or bevacizumab injection after initial, unsuccessful treatment showed some detrimental, neurodevelopmental effects.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Reduction in methane emissions to the Earth's atmosphere is a critical strategy for tackling climate change. It is well established that anaerobic oxidation of methane (AOM) associated with sulfate ...reduction functions as an important methane sink in marine sediments. However, recent findings show that AOM uses diverse electron acceptors across a range of habitats, prompting examination of the potential role of AOM in mitigation of methane emissions and global climate change in non-marine environments. Methane is also a valuable energy source, widely used for production of electricity. Recent studies suggest that AOM could be used to produce liquid fuels/chemicals. The potential involvement of CO
2
in product formation is particularly exciting as methane bioconversion could act as a net sink of CO
2
. The discovery that AOM is able to transfer electrons to solid electron acceptors suggests that methane may be a suitable source of electrons for a bioelectrochemical, biosynthesis cell. In addition, AOM has been used for pollution control and environmental remediation, such as nitrogen removal from contaminated water. Herein, we review and discuss implications of the latest scientific discoveries in AOM for methane emissions from aquatic and terrestrial environments, and methane as a feedstock for various biotechnology platforms.
Anaerobic oxidation of methane (AOM) is a crucial bioprocess in global methane mitigation. Adoption of AOM in an engineered system provides an opportunity for the development of methane-based biotechnologies.
•Biogenic ROS triggered oxidative degradation of SMX in a methane-fed biofilm.•Active pMMO and AMO were associated with ROS production.•ROS mainly attacked aniline group of SMX with accumulation of ...3A5MI.•Methylosarcina and Ca. Nitrosotenuis likely collaborated as SMX degraders.
Although microorganisms carrying copper-containing membrane-bound monooxygenase (CuMMOs), such as particulate methane monooxygenase (pMMO) and ammonia monooxygenase (AMO), have been extensively documented for their capability to degrade organic micropollutants (OMPs), the underlying reactive mechanism remains elusive. In this study, we for the first time demonstrate biogenic reactive oxygen species (ROS) play important roles in the degradation of sulfamethoxazole (SMX), a representative OMP, within a methane-fed biofilm. Highly-efficient and consistent SMX biodegradation was achieved in a CH4-based membrane biofilm reactor (MBfR), manifesting a remarkable SMX removal rate of 1210.6 ± 39.0 μg·L−1·d−1. Enzyme inhibition and ROS clearance experiments confirmed the significant contribution of ROS, which were generated through the catalytic reaction of pMMO and AMO enzymes, in facilitating SMX degradation. Through a combination of density functional theory (DFT) calculations, electron paramagnetic resonance (EPR) analysis, and transformation product detection, we elucidated that the ROS primarily targeted the aniline group in the SMX molecule, inducing the formation of aromatic radicals and its progressive mineralization. In contrast, the isoxazole-ring was not susceptible to electrophilic ROS attacks, leading to accumulation of 3-amino-5-methylisoxazole (3A5MI). Furthermore, microbiological analysis suggested Methylosarcina (a methanotroph) and Candidatus Nitrosotenuis (an ammonia-oxidizing archaea) collaborated as the SMX degraders, who carried highly conserved and expressed CuMMOs (pMMO and AMO) for ROS generation, thereby triggering the oxidative degradation of SMX. This study deciphers SMX biodegradation through a fresh perspective of free radical chemistry, and concurrently providing a theoretical framework for the advancement of environmental biotechnologies aimed at OMP removal.
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Discussions on the positive effect of nano-sized metal addition to dark fermentation biohydrogen production have been raised but the real stimulation mechanism remains unclear. In this study, ...biohydrogen production enhancement by nanoparticle metal addition was tested using a strain of a known hydrogen producer, Clostridium pasteurianum. Gene expression and growth activity were evaluated. Biochemical hydrogen potential tests on the added TiO2 and Fe nanoparticles were performed at 35 °C with various metal concentrations (control and 50, 100, 200, 400, and 800 ppm). Comparison with the control showed that adding 50 ppm Fe nanoparticles could significantly increase the hydrogen production, which was expressed H2 gas volume, by 24.9%. The corresponding hydrogen production rate increased to 8.7 H2-L/L-d. This positive stimulation effect gradually decreased with increasing metal concentrations added. The effect eventually caused inhibition when the metal concentration reached 400 and 800 ppm. The highest maximum hydrogen production rate (Rmax) and the potential hydrogen production (P) in the simulation kinetic model were 45.2 mL/h and 255.7 mL, respectively. Despite increase in the gas production, metal addition did not increase the overall hydrogen yield (mol H2/mol xylose). Hence, this stimulation may not occur on the microorganism metabolism level. Analysis of gene expression indicated that addition of Fe nanoparticles did not remarkably improve the hydrogen enzyme activity of C. pasteurianum. Overall, hydrogen production stimulated by adding nano-metals was not directly related to enzyme activity improvement.
•Addition of magnetic hematite nanoparticle could increase hydrogen production of dark fermentation.•Addition of NP-Fe did not remarkably improve enzyme activity despite an improvement of hydrogen gas production.•Hydrogen production stimulated by adding nano-metals might due to the enhancement of electron transfer.
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