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TIGIT is an immune checkpoint receptor that is expressed on subsets of activated T cells and natural killer (NK) cells. Several ligands for TIGIT, including poliovirus receptor (PVR), are expressed on cancer cells and mediate inhibitory signaling to suppress antitumor activities of the immune cells. Many studies support that the TIGIT signaling is a potential target for cancer immunotherapy. We developed an IgG4-type monoclonal antibody against human TIGIT, designated as MG1131, using a phage display library of single-chain variable fragments (scFvs). MG1131 interacts with TIGIT much more tightly than PVR does. The crystal structure of a scFv version of MG1131 bound to TIGIT was determined, showing that MG1131 could block the PVR-TIGIT interaction and thus the immunosuppressive signaling of TIGIT. Consistently, MG1131 is bound to TIGIT-expressing cells and interferes with PVR binding to these cells. Moreover, MG1131 increased NK cell-mediated tumor killing activities, inhibited immunosuppressive activity of regulatory T (Treg) cells from healthy donors, and restored interferon-γ secretion from peripheral blood mononuclear cells derived from multiple myeloma patients. MG1131 also increased T cell infiltration to the tumor site and inhibited tumor growth in mice. Collectively, these data indicate that MG1131 modulates the effector functions of T cells and NK cells positively and Treg cells negatively.

Abstract Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders that are highly heterogeneous in clinical symptoms as well as etiologies. Mutations in SHANK2 are associated with ASD and accordingly, Shank2 knockout mouse shows ASD-like behavioral phenotypes, including social deficits. Intriguingly, two lines of Shank2 knockout (KO) mouse generated by deleting different exons (exon 6–7 or exon 7) showed distinct cellular phenotypes. Previously, we compared gene expressions between Shank2 KOs lacking exon 6–7 (e6–7 KO) and KOs lacking exon 7 (e7 KO) by performing RNA-seq. In this study, we expanded transcriptomic analyses to identify novel transcriptional variants in the KO mice. We found prominent expression of a novel exon (exon 4′ or e4’) between the existing exons 4 and 5 in the Shank2 e6–7 KO model. Expression of the transcriptional variant harboring this novel exon was confirmed by RT-PCR and western blotting. These findings suggest that the novel variant may function as a modifier gene, which contributes to the differences between the two Shank2 mutant lines. Furthermore, our result further represents an example of genetic compensation that may lead to phenotypic heterogeneity among ASD patients with mutations in the same gene.

Abstract Background Effective control of shot-hole disease in flowering cherries is challenging because of multiple causative pathogens (bacteria and fungi). Bacillus species are well-known for their ability to control plant pathogens; therefore, biological control potential of a Bacillus isolate, B. velezensis 8–2, against SH disease on flowering cherry trees was investigated. Results This study revealed strong antimicrobial activity of Bacillus velezensis 8–2 against various plant pathogenic bacteria and fungi, particularly focusing on Xanthomonas arboricola pv. pruni (Xap) and Mycosphaerella cerasella (Mc), which cause shot-hole (SH) disease in flowering cherry trees. In vitro assays showed that the fermentation filtrate of B. velezensis 8–2 inhibited bacterial and fungal growth with minimum inhibitory concentrations of 1.25–10% and 2.5–10%, respectively. UPLC-Q–Orbitrap–MS analysis revealed that B. velezensis 8–2 produced antagonistic compounds, including polyketides (difficidin and oxydifficidin) and cyclic lipopeptides (iturin A, fengycin, and surfatin). To enhance antimicrobial activity, fermentation parameters for optimal production of two antibacterial and three antifungal compounds were investigated in a 5 L jar fermenter. By regulating the agitation speed to sustain the state of vegetative cells, the production period was extended by 20 h at 400 rpm, resulting in maximum yields of 86.6 μg/mL for difficidin and 150.0 μg/mL for oxydifficidin within a 72 h fermentation period. In a field trial, a 500-fold diluted 10% suspension concentrate formulation of B. velezensis 8–2 effectively inhibited the development of SH disease, demonstrating 66.6% disease control and a 90.2% disease symptoms reduction. Conclusions This is the first report to assess the disease control efficacy of B. velezensis for the biocontrol of SH disease in the field. These results suggest that the application of B. velezensis 8–2 could serve as a practical alternative for managing various bacterial and fungal diseases, including the management of SH disease in flowering cherry trees. Graphical Abstract

Lactic acid bacteria (LAB) are being used for probiotic and starter cultures to prevent global damage to microbial cells. To retain the benefits of LAB in the commercially used powdered form, highly efficient cryoprotective agents are required during the manufacturing process. This study suggests a novel cryoprotective agent derived from Jerusalem artichoke (JA; Helianthus tuberous L.) and describes the mechanism of cryoprotective effect improvement by sonication treatment. The cryoprotective effect of JA extract was verified by examining the viability of Leuconostoc mesenteroides WiKim33 after freeze-drying (FD). Sonication of JA extract improved the cryoprotective effect. Sonication reduced fructose and glucose contents, which increased the induction of critical damage during FD by 15.84% and 46.81%, respectively. The cryoprotective effects of JA and sonication-treated JA extracts were determined using the viable cell count of Leu. mesenteroides WiKim33. Immediately after FD and storage for 24 weeks, the viability of Leu. mesenteroides WiKim33 with JA extract was 82.8% and 76.3%, respectively, while that of the sonication-treated JA extract was 95.2% and 88.8%, respectively. Our results show that reduction in specific monosaccharides was correlated with improved cryoprotective effect. This study adopted sonication as a novel treatment for improving the cryoprotective effect and verified its efficiency.

Xanthophylls, a yellow pigment belonging to the carotenoid family, have attracted much attention for industrial applications due to their versatile nature. We report the isolation of a homo xanthophyll pigment-producing marine bacterium, identified as the Erythrobacter sp. SDW2 strain, from coastal seawater. The isolated Erythrobacter sp. SDW2 strain can produce 263 ± 12.9 mg/L (89.7 ± 5.4 mg/g dry cell weight) of yellow xanthophyll pigment from 5 g/L of glucose. Moreover, the xanthophyll pigment produced by the SDW2 strain exhibits remarkable antioxidative activities, confirmed by the DPPH (73.4 ± 1.4%) and ABTS (84.9 ± 0.7%) assays. These results suggest that the yellow xanthophyll pigment-producing Erythrobacter sp. SDW2 strain could be a promising industrial microorganism for producing marine-derived bioactive compounds with potential for foods, cosmetics, and pharmaceuticals.

This paper describes a novel chromatographic method for efficient removal of anionic dyes from aqueous solutions. Chitosan-coated Fe3O4 nanoparticles can easily be immobilized on a dextran gel column. Single elution of Evans Blue (EB) solution to the nanoadsorbent-incorporated columns provides high removal efficiency with a maximum adsorption capacity of 243.9 mg/g. We also investigated the influence of initial concentration and solution pH on the removal efficiency of EB. The electrostatic interaction between the adsorbent surface and negatively charged sulfate groups on EB molecules promotes the efficient adsorption of dyes. The equilibrium data matched well with the Langmuir isotherm model, which indicated monolayer dye adsorption onto the adsorbent surface. To extend the application of the current method, we performed further adsorption experiments using other anionic dyes of different colors (Cy5.5, Acid Yellow 25, Acid Green 25, and Acid Red 1). All of these molecules can efficiently be captured under continuous flow conditions, with higher removal efficiency obtained with more negatively charged dyes. These findings clearly demonstrate that the present approach is a useful method for the removal of anionic dye contaminants in aqueous media by adsorption.

As concerns about public health and environmental problems regarding contamination by toxic substances increase worldwide, the development of a highly effective and specific treatment method is imperative. Although physicochemical arsenic treatment methods have been developed, microbial in vivo remediation processes using live cell fabricated nanoparticles have not yet been reported. Herein, we report the development of magnetic iron nanoparticles immobilized an extremophilic microorganism, Deinococcus radiodurans R1, capable of removing toxic arsenic species. First, in vivo synthesis of magnetic iron nanoparticles was successfully achieved with the D. radiodurans R1 strain and characterized by scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX), dynamic light scattering (DLS), zeta-potential, Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) analysis. Second, the maximum removal capacity of the magnetic iron nanoparticle-immobilized D. radiodurans R1 strain (DR-FeNPs) for arsenic [As(V)] was evaluated under the optimized conditions. Finally, the removal capacity of DR-FeNPs in the presence of various competitive anions was also investigated to simulate the practical application. More than 98% of As(V) was efficiently removed by DR-FeNPs within 1 h, and the removal efficiency was stably maintained for up to 32 h (98.97%). Furthermore, the possibility of recovery of DR-FeNPs after use was also suggested using magnets as a proof-of-concept.

Fermentative production of aromatic polyesters from glucose has been unsuccessful. Here, the authors achieve the objective by one-step fermentation of metabolically engineered E. coli expressing a isocaprenoyl-CoA:2-hydroxyisocaproate CoA-transferase and an evolved polyhydroxyalkanoate synthase.

As concerns are increasing about drinking water contamination with heavy metals, we investigated the possible use of a pellicle (floating biofilm)-like biofilm-producing microorganism as a biosorbent for the treatment of Pb(II) in aqueous solutions. The bacterial pellicle-producing Methylobacterium hispanicum EM2 strain (EM2) was newly isolated from mine tailing soil, and we investigated its use as a biosorbent for treating a Pb(II)-contaminated aqueous solution. The EM2 strain was strongly resistant to Pb(II) up to a concentration of 800 mg/L, and achieved remarkable adsorption performance (adsorption rate and maximum adsorption capacity of 96% ± 3.2% and 79.84 mg/g, respectively) under optimal conditions (pH, biomass content, contact time, and initial Pb(II) concentration of 7.1 g/L, 60 min, and 10 mg/L, respectively). The adsorption of Pb(II) was characterized by scanning electron microscopy-energy dispersive x-ray spectroscopy and Fourier-transform infrared analysis. The equilibrium data matched the Freundlich isotherm model well, indicating the occurrence of multilayer adsorption of Pb(II) onto the heterogeneous surface of the EM2 strain, which was also consistent with the pseudo-second-order kinetic model (R2 = 0.98). The high Pb(II) removal efficiency was also confirmed by conducting an adsorption experiment using Pb(II)-contaminated industrial wastewater.

Increasing concerns regarding the adverse effects of radioactive iodine waste have inspired the development of a highly efficient and sustainable desalination process for the treatment of radioactive iodine-contaminated water. Because of the high affinity of silver towards iodine species, silver nanoparticles immobilized on a cellulose acetate membrane (Ag-CAM) and biogenic silver nanoparticles containing the radiation-resistant bacterium Deinococcus radiodurans (Ag-DR) were developed and investigated for desalination performance in removing radioactive iodines from water. A simple filtration of radioactive iodine using Ag-CAM under continuous in-flow conditions (approximately 1.5 mL/s) provided an excellent removal efficiency (>99%) as well as iodide anion-selectivity. In the bioremediation study, the radioactive iodine was rapidly captured by Ag-DR in the presence of high concentration of competing anions in a short time. The results from both procedures can be visualized by using single-photon emission computed tomography (SPECT) scanning. This work presents a promising desalination method for the removal of radioactive iodine and a practical application model for remediating radioelement-contaminated waters.