Imazethapyr (IM) is a chiral herbicide and a widely used racemic mixture. This report investigated the enantioselectivity between R- and S-IM in rice and explored its causative mechanism at the physiological and molecular levels. The results suggested that R-IM inhibited acetolactate synthase (ALS) activity to a greater extent than S-IM, which reduced the synthesis of branched-chain amino acids (BCAAs). Additionally, most other amino acids showed enantioselectivity. On the cellular level, R-IM showed stronger toxicity against protoplasts than S-IM. A gene transcription profile analysis showed that gene transcripts in many metabolic pathways, including amino acid metabolism, photosynthesis, starch and sugar metabolism, and the tricarboxylic acid cycle displayed enantioselectivity between the IM enantiomers. R-IM regulated more genes more strongly than S-IM. This study suggested that R-IM has stronger toxicity against plants than S-IM; this toxicity is caused not only by changing targeted enzyme activity and amino acid synthesis, but also by affecting gene transcription in other metabolic pathways directly or indirectly in an enantioselective manner.
Autoimmune diseases, allergies, transplant rejections, generation of antidrug antibodies, and chronic inflammatory diseases have impacted a large group of people across the globe. Conventional treatments and therapies often use systemic or broad immunosuppression with serious efficacy and safety issues. Tolerogenic vaccines represent a concept that has been extended from their traditional immune-modulating function to induction of antigen-specific tolerance through the generation of regulatory T cells. Without impairing immune homeostasis, tolerogenic vaccines dampen inflammation and induce tolerogenic regulation. However, achieving the desired potency of tolerogenic vaccines as preventive and therapeutic modalities calls for precise manipulation of the immune microenvironment and control over the tolerogenic responses against the autoantigens, allergens, and/or alloantigens. Engineered nano-/microparticles possess desirable design features that can bolster targeted immune regulation and enhance the induction of antigen-specific tolerance. Thus, particle-based tolerogenic vaccines hold great promise in clinical translation for future treatment of aforementioned immune disorders. In this review, we highlight the main strategies to employ particles as exciting tolerogenic vaccines, with a focus on the particles' role in facilitating the induction of antigen-specific tolerance. We describe the particle design features that facilitate their usage and discuss the challenges and opportunities for designing next-generation particle-based tolerogenic vaccines with robust efficacy to promote antigen-specific tolerance for immunotherapy.
Cellulose nanocrystals (CNCs) have attracted much interest due to their unique optical property, rich resource, environment friendliness, and templating potentials. CNCs have been reported as novel photonic humidity sensors, which are unfortunately limited by the dissolution and unideal moisture absorption of CNCs. We, in this study, developed a high-performance photonic humidity composite sensor that consisted of CNCs and polyacrylamide; chemical bonding was induced between the two components by using glutaraldehyde as a bridging agent. The composites inherited the chiral nematic structure of CNCs and maintained it well through a cycling test. A distinct color change was observed for these composites used as a humidity indicator; the change was caused by polyacrylamide swelling with water and thus enlarging the helical pitch of the chiral nematic structure. The composites showed no degradation of the sensing performance through cycling. The excellent cycling stability was attributed to the bonding between polyacrylamide and CNCs. This composite strategy can extend to the development of other photonic indicators.
Efficiency is crucial to the online recommender systems, especially for the ones which needs to deal with tens of millions of users and items. Because representing users and items as binary vectors for Collaborative Filtering (CF) can achieve fast user-item affinity computation in the Hamming space, in recent years, we have witnessed an emerging research effort in exploiting binary hashing techniques for CF methods. However, CF with binary codes naturally suffers from low accuracy due to limited representation capability in each bit, which impedes it from modeling complex structure of the data.
Abstract Background Cryptococcal meningitis (CM) is an inflammatory mycosis of the central nervous system caused by meninge infection or brain parenchyma with Cryptococcus species. It is associated with high morbidity and mortality, and patients with acquired immune deficiency syndrome are particularly susceptible. There have been increasing reports of CM in HIV-negative patients in China over the last few years. Case presentation A 31-year-old healthy Chinese male presented with fever and gradually developed headache, projectile vomiting, and other manifestations that were later confirmed as Cryptococcus gattii meningoencephalitis. However, multiple disease changes occurred during the course of treatment, and the regimen was accordingly modified after the diagnosis of post-infectious inflammatory response syndrome (PIIRS). The patient eventually recovered. Conclusion There has been a growing trend in the incidence of C. gattii meningoencephalitis in HIV-negative patients. It shows rapid onset and severe prognosis. This case report can provide a reference to treat PIIRS following CM in HIV-negative patients.
The investigation of enzyme reaction kinetics in nanoconfined spaces mimicking the conditions in living systems is of great significance. Here, a nanofluidics chip integrated with an electrochemical detector has been designed for studying "free state" enzyme reaction kinetics in nanoconfinement. The nanofluidics chip is fabricated using the UV-ablation technique developed in our group. The enzyme and substrate solutions are simultaneously supplied from two single streams into a nanochannel through a Y-shaped junction. The laminar flow forms in the front of the nanochannel, then the two liquids fully mix at their downstream where a homogeneous enzyme reaction occurs. The "free state" enzyme reaction kinetics in nanoconfinement can thus be investigated in this laminar flow based nanofluidics device. For demonstration, glucose oxidase (GOx) is chosen as the model enzyme, which catalyzes the oxidation of beta-D-glucose. The reaction product hydrogen peroxide (H2O2) can be electrochemically detected by a microelectrode aligning to the end of nanochannel. The steady-state electrochemical current responding to various glucose concentrations is used to evaluate the activity of the "free state" GOx under nanoconfinement conditions. The effect of liquid flow rate, enzyme concentration, and nanoconfinement on reaction kinetics has been studied in detail. Results show that the "free state" GOx activity increases significantly compared to the immobilized enzyme and bath system, and the GOx reaction rate in the nanochannel is two-fold faster than that in bulk solution, demonstrating the importance of "free state" and spatial confinement for the enzyme reaction kinetics. The present approach provides an effective method for exploiting the "free state" enzyme activity in nanospatial confinement.
In our study titled "Retinoids inhibit ferroptosis through their radical-trapping properties and RAR-SCD-mediated monounsaturated fatty acids generation", we compared the gene expression pattern (Figure 4) and abundance of lipids (Figure 5 and S5) between Cas-NC and RETSAT-KO A549 cells treated with DMSO, IKE, or RSL3 using RNA-Seq and pseudotargeted lipidomic analysis respectively.
Mycelial pellets are microbial particles formed during fungi culturing and their formation mechanisms are still under investigation. Spore aggregation is often considered as a crucial step for fungi to form mycelial pellets. In this work, the pellet formation processes of three fungi were investigated for proving the mycelial pellet formation without spores, and a marine-derived Aspergillus niger was selected as an example for the mechanism studies of mycelial pellet formation, and detailed processes of mycelium agglomeration and pellet formation were recorded. Experimental results showed that mycelial pellets can be formed directly from hyphae and the spore aggregation may not be an essential step. Moreover, the culture media pH had substantial effects on the pellet formation processes. Scanning electron microscope and infrared spectroscopy results indicated that the decrease of pelletization capacity was related to the change of extracellular polymeric substances. However, mycelium could not grow into mycelial pellets after adding 100 g/L talc into the culture media, while the spore inoculation method could still result in the formation of mycelial pellets under the same condition. This result indicated that although spore aggregation may not be essential, it is likely an enhancing factor for the mycelial pellet formation.
ABSTRACT In three Escherichia coli mutants, a change (Ala-51 to Val) in the gyrase A protein outside the standard quinolone resistance-determining region (QRDR) lowered the level of quinolone susceptibility more than changes at amino acids 67, 82, 84, and 106 did. Revision of the QRDR to include amino acid 51 is indicated.
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