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GSK-3β plays a critical role in regulating the Wnt/β-catenin signaling pathway, and manipulating GSK-3β in dendritic cells (DCs) has been shown to improve the antitumor efficacy of DC vaccines. Since the inhibition of GSK-3β leads to the activation of β-catenin, we hypothesize that blocking GSK-3β in DCs negatively regulates DC-mediated CD8 T cell immunity and antitumor immunity. Using CD11c-GSK-3β−/− conditional knockout mice in which GSK-3β is genetically deleted in CD11c-expressing DCs, we surprisingly found that the deletion of GSK-3β in DCs resulted in increased antitumor immunity, which contradicted our initial expectation of reduced antitumor immunity due to the presumed upregulation of β-catenin in DCs. Indeed, we found by both Western blot and flow cytometry that the deletion of GSK-3β in DCs did not lead to augmented expression of β-catenin protein, suggesting that GSK-3β exerts its function independent of β-catenin. Supporting this notion, our single-cell RNA sequencing (scRNA-seq) analysis revealed that GSK-3β-deficient DCs exhibited distinct gene expression patterns with minimally overlapping differentially expressed genes (DEGs) compared to DCs with activated β-catenin. This suggests that the deletion of GSK-3β in DCs is unlikely to lead to upregulation of β-catenin at the transcriptional level. Consistent with enhanced antitumor immunity, we also found that CD11c-GSK-3β−/− mice exhibited significantly augmented cross-priming of antigen-specific CD8 T cells following DC-targeted vaccines. We further found that the deletion of GSK-3β in DCs completely abrogated memory CD8 T cell responses, suggesting that GSK-3β in DCs also plays a negative role in regulating the differentiation and/or maintenance of memory CD8 T cells. scRNA-seq analysis further revealed that although the deletion of GSK-3β in DCs positively regulated transcriptional programs for effector differentiation and function of primed antigen-specific CD8 T cells in CD11c-GSK-3β−/− mice during the priming phase, it resulted in significantly reduced antigen-specific memory CD8 T cells, consistent with diminished memory responses. Taken together, our data demonstrate that GSK-3β in DCs has opposite functions in regulating cross-priming and memory CD8 T cell responses, and GSK-3β exerts its functions independent of its regulation of β-catenin. These novel insights suggest that targeting GSK-3β in cancer immunotherapies must consider its dual role in CD8 T cell responses. [ABSTRACT FROM AUTHOR]

Soybean mosaic virus (SMV) is one of the main pathogens that can negatively affect soybean production and quality. To study the gene regulatory network of soybeans in response to SMV SC15, the resistant line X149 and susceptible line X97 were subjected to transcriptome analysis at 0, 2, 8, 12, 24, and 48 h post-inoculation (hpi). Differential expression analysis revealed that 10,190 differentially expressed genes (DEGs) responded to SC15 infection. Weighted gene co-expression network analysis (WGCNA) was performed to identify highly related resistance gene modules; in total, eight modules, including 2256 DEGs, were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of 2256 DEGs revealed that the genes significantly clustered into resistance-related pathways, such as the plant–pathogen interaction pathway, mitogen-activated protein kinases (MAPK) signaling pathway, and plant hormone signal transduction pathway. Among these pathways, we found that the flg22, Ca2+, hydrogen peroxide (H2O2), and abscisic acid (ABA) regulatory pathways were fully covered by 36 DEGs. Among the 36 DEGs, the gene Glyma.01G225100 (protein phosphatase 2C, PP2C) in the ABA regulatory pathway, the gene Glyma.16G031900 (WRKY transcription factor 22, WRKY22) in Ca2+ and H2O2 regulatory pathways, and the gene Glyma.04G175300 (calcium-dependent protein kinase, CDPK) in Ca2+ regulatory pathways were highly connected hub genes. These results indicate that the resistance of X149 to SC15 may depend on the positive regulation of flg22, Ca2+, H2O2, and ABA regulatory pathways. Our study further showed that superoxide dismutase (SOD) activity, H2O2 content, and catalase (CAT) and peroxidase (POD) activities were significantly up-regulated in the resistant line X149 compared with those in 0 hpi. This finding indicates that the H2O2 regulatory pathway might be dependent on flg22- and Ca2+-pathway-induced ROS generation. In addition, two hub genes, Glyma.07G190100 (encoding F-box protein) and Glyma.12G185400 (encoding calmodulin-like proteins, CMLs), were also identified and they could positively regulate X149 resistance. This study provides pathways for further investigation of SMV resistance mechanisms in soybean. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated that β-catenin in dendritic cells (DCs) serves as a key mediator in promoting both CD4 and CD8 T cell tolerance, although the mechanisms underlying how β-catenin exerts its functions remain incompletely understood. Here, we report that activation of β-catenin leads to the up-regulation of inhibitory molecule T-cell immunoglobulin and mucin domain 3 (Tim-3) in type 1 conventional DCs (cDC1s). Using a cDC1-targeted vaccine model with anti-DEC-205 engineered to express the melanoma antigen human gp100 (anti-DEC-205-hgp100), we demonstrated that CD11c-β-cateninactive mice exhibited impaired cross-priming and memory responses of gp100-specific CD8 T (Pmel-1) cells upon immunization with anti-DEC-205-hgp100. Single-cell RNA sequencing (scRNA-seq) analysis revealed that β-catenin in DCs negatively regulated transcription programs for effector function and proliferation of primed Pmel-1 cells, correlating with suppressed CD8 T cell immunity in CD11c-β-cateninactive mice. Further experiments showed that treating CD11c-β-cateninactive mice with an anti-Tim-3 antibody upon anti-DEC-205-hgp100 vaccination led to restored cross-priming and memory responses of gp100-specific CD8 T cells, suggesting that anti-Tim-3 treatment likely synergizes with DC vaccines to improve their efficacy. Indeed, treating B16F10-bearing mice with DC vaccines using anti-DEC-205-hgp100 in combination with anti-Tim-3 treatment resulted in significantly reduced tumor growth compared with treatment with the DC vaccine alone. Taken together, we identified the β-catenin/Tim-3 axis as a potentially novel mechanism to inhibit anti-tumor CD8 T cell immunity and that combination immunotherapy of a DC-targeted vaccine with anti-Tim-3 treatment leads to improved anti-tumor efficacy. [ABSTRACT FROM AUTHOR]

An asymmetric transfer hydrogenation of 2‐oxazolones in the presence of a chiral diamine ruthenium catalyst with potassium formate as a hydrogen source and potassium carbonate as an additive in 2,2,2‐trifluoroethanol is described. A series of chiral 2‐oxazolidinones were obtained with 29%–95% yields and 86%–>99% ee's. Furthermore, gram‐scale synthesis of chiral 2‐oxazolidinone and its downstream derivatizations demonstrate the practicality of this method. [ABSTRACT FROM AUTHOR]

This paper proposes a hybrid control scheme that combines fractional-order sliding-mode control (FOSMC) with radial basis function neural network adaptive damping passivity-based control (RBFPBC) for modular multilevel converters (MMC) under non-ideal operating conditions. According to the passive control theory, we establish the Euler–Lagrange (EL) models of positive and negative sequences based on the unbalanced grid. A passivity-based controller that satisfies the energy dissipation law is designed. To enable rapid convergence of the system energy storage function, a radial basis function neural network (RBFNN) is introduced to adjust the injection damping adaptively. Additionally, a fractional-order sliding-mode controller (FOSMC) is designed. The fractional-order sliding mode surface used can improve tracking performance, and effectively suppressed the undesirable chattering phenomenon compared to the traditional sliding-mode control (SMC). Finally, combining the two control methods can effectively solve the issue of passivity-based control (PBC) being too dependent on parameters. The proposed hybrid control scheme enhances the ability of the system to resist disturbances, and improves its overall robustness. Simulation results demonstrate the feasibility and effectiveness of this control method. [ABSTRACT FROM AUTHOR]

Simple Summary: Controlling epigenetic signals for mediating the homeostatic immune response in skin-residing Langerhans cells (LCs) ontogeny, maintenance, and function are largely not determined. Here, we demonstrated that the epigenetic regulator miR-23a not only plays an indispensable role for LC antigen uptake but is also crucial for bone marrow-derived LC repopulation during the inflammatory condition. During this process, miR-23a may regulate LC phagocytosis by mediating efferocytosis and endocytosis-mediated targets as well as LCs repopulation via targeting Fas and Bcl-2 family proapoptotic molecules. Instead, miR-23a did not demonstrate playing any role in LC development and postnatal homeostasis. Thus, the context-dependent regulatory role of miR-23a in LCs may represent an extra-epigenetic layer for incorporating TGF-β and PU.1-mediated regulation during steady-state and inflammation-induced repopulation. Langerhans cells (LCs) are skin-resident macrophage that act similarly to dendritic cells for controlling adaptive immunity and immune tolerance in the skin, and they are key players in the development of numerous skin diseases. While TGF-β and related downstream signaling pathways are known to control numerous aspects of LC biology, little is known about the epigenetic signals that coordinate cell signaling during LC ontogeny, maintenance, and function. Our previous studies in a total miRNA deletion mouse model showed that miRNAs are critically involved in embryonic LC development and postnatal LC homeostasis; however, the specific miRNA(s) that regulate LCs remain unknown. miR-23a is the first member of the miR-23a-27a-24-2 cluster, a direct downstream target of PU.1 and TGF-b, which regulate the determination of myeloid versus lymphoid fates. Therefore, we used a myeloid-specific miR-23a deletion mouse model to explore whether and how miR-23a affects LC ontogeny and function in the skin. We observed the indispensable role of miR-23a in LC antigen uptake and inflammation-induced LC epidermal repopulation; however, embryonic LC development and postnatal homeostasis were not affected by cells lacking miR23a. Our results suggest that miR-23a controls LC phagocytosis by targeting molecules that regulate efferocytosis and endocytosis, whereas miR-23a promotes homeostasis in bone marrow-derived LCs that repopulate the skin after inflammatory insult by targeting Fas and Bcl-2 family proapoptotic molecules. Collectively, the context-dependent regulatory role of miR-23a in LCs represents an extra-epigenetic layer that incorporates TGF-b- and PU.1-mediated regulation during steady-state and inflammation-induced repopulation. [ABSTRACT FROM AUTHOR]

Polyamide reverse osmosis membranes are indispensable for the worldwide clean water supply. Incorporation of nanomaterials into polyamide separation layer provides an evident methodology to enhance the water flux. However, the desalination performance would be compromised by the inadequate compatibility between the nanomaterial and the polyamide matrix. In this work, we propose a straightforward strategy to use covalent organic frameworks (COF) nanofibers as the efficient nanofiller for the fabrication of high flux polyamide membranes. The COF nanofibers featuring crystalline structures, large surface area and well‐defined micropores are synthesized by a surfactant‐mediated solvothermal method. It is found that the COF nanofibers are able to mediate the interfacial polymerization process via the controlled release of amine molecules. This creates the reduced thickness of the polyamide separation layer. Moreover, the rigid and permanent nanopores of COF could serve as additional channels for water permeation. Benefitting from the low thickness and the additional channels, thus fabricated membranes exhibit a significantly enhanced water flux, while maintaining a slightly improved NaCl rejection. Our work is expected to provide a new insight for the design and fabrication of advanced polyamide reverse osmosis membranes. [ABSTRACT FROM AUTHOR]

Organic solvent nanofiltration (OSN) has become increasingly important in petrochemical and pharmaceutical industries, demanding superior and robust membranes. Herein, we report advanced OSN processes by designing three‐dimensional covalent organic framework (3D COF) membranes through moderated interfacial crystallization. Nanoporous supports work as the moderator allowing the crystallization of 3D COF membranes. The 3D COF features sub‐nanometer and anti‐swelling channels, affording a sharp selectivity to fine targets with an exceptionally high and stable methanol permeance. Thus‐synthesized membrane exhibits a record stability against high‐concentration feeds and long‐term operation for ≈1000 h. Moreover, we unambiguously demonstrate that our membrane holds excellent practicality in purifying active pharmaceutical ingredients from organic liquids. This work reveals the great potential of distinctive 3D COFs in producing prominent OSN membranes for industrial applications. [ABSTRACT FROM AUTHOR]

Owing to the biological significance and great synthetic value of chiral lactones and their derivatives, increasing attention has been paid to developing effective synthetic methods for chiral lactones. We herein report an efficient asymmetric hydrogenation of benzo-fused ketoesters, γ-ketoesters and biaryl-bridged ketoesters catalyzed by chiral iridium complexes bearing ferrocene-based chiral ligands, furnishing a series of chiral lactones in superb yields and excellent enantioselectivities (up to 99% yields and up to 99% ee). [ABSTRACT FROM AUTHOR]

A heterostructured covalent organic framework (COF) membrane is synthesized via in situ linker exchange. Narrowed pores can be formed at the interface between two types of COFs by adjusting the linker exchange duration. The resultant COF membrane demonstrates a high rejection rate toward Na2SO4 of up to 97%. [ABSTRACT FROM AUTHOR]

Oxygen evolution reaction on a graphene sheet at negative potential is observed using surface plasmon resonance microscopy (SPRM). It is found that oxygen nanobubbles are evolved at negative potential due to the disproportion reaction of superoxide originated from the reduced dissolved oxygen, suggesting that graphene acts as a superoxide dismutase (SOD) mimic. SPRM reveals that the catalytic sites distribute at the edge and the bulk of graphene. Atomic force microscopy suggests that the active sites for bubble evolution in the bulk of graphene are located at internal edge originated from the holes in the graphene rather than the metal oxide residues remained on the graphene sheet. The metal oxide nanoparticles on the graphene sheet are not the direct active sites but also play important roles in promoting the catalysis by increasing the superoxide concentration through an electrocatalyzed Fenton reaction. This work also presents the first experimental evidence that the catalysis of graphene is generated from the edge effect in an in operando manner. The SPRM represents a universal tool to reveal the catalytic mechanism at microscale, and it is hoped to discover more exciting reactions on nanomaterials due to its label free feature, high sensitivity, and versatility to most of materials. [Display omitted] • Oxygen evolution reaction was observed at negative potential on a graphene sheet. • This reaction was imaged at microscale in an in-operando manner. • The edge of the graphene is the active site for oxygent nanobubbles evolution. • The metal oxides on the graphene sheet are not the active sites, but promote this reaction. [ABSTRACT FROM AUTHOR]

A novel synthetic route was developed for the construction of a chiral cis-hexahydro-γ-carboline derivative through Ir/ZhaoPhos-catalyzed asymmetric hydrogenation of corresponding tetrahydro-γ-carboline with high yields (up to 99% yield), excellent diastereoselectivities (up to >99 : 1 dr) and enantioselectivities (up to 99% ee), and high substrate-to-catalyst ratios (up to 5000). [ABSTRACT FROM AUTHOR]

A straightforward asymmetric transfer hydrogenation for accessing enantiomerically enriched secondary benzyl alcohols involving free phenolic hydroxyl group(s) under mild conditions was developed. Various of optical pure aryl alcohols with a remarkable functional group compatibility were achieved with 78%-97% yields, 84%->99% ee's and up to 10 000 TON. This rhodium-catalyzed reaction could be performed in a gram-scale without loss of the efficiency. Furthermore, the synthetic utility has also been demonstrated in the asymmetric synthesis of (S)-adrenaline and (S)-phenylephrine., (© 2024 Wiley‐VCH GmbH.)

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition characterized by painful nodules, abscesses, and scarring, predominantly affecting intertriginous regions and it is often underdiagnosed. This study aimed to utilize single cell RNA and cell-surface protein sequencing (CITE-Seq) to delineate the immune composition of circulating cells in Hidradenitis suppurativa (HS) peripheral blood compared to healthy controls. CITE-Seq was used to analyze the gene and protein expression profiles of peripheral blood mononuclear cells (PBMCs) from 9 HS and 29 healthy controls. The study identified significant differences cell composition between HS patients and healthy controls, including increased proportions of CD14+ and CD16+ monocytes, cDC2, plasmablasts, and proliferating CD4+ T cells in HS patients. Differential expression analysis revealed upregulation of inflammatory markers such as TNF, IL1B , and NF-κB in monocytes, as well as chemokines and cell adhesion molecules involved in immune cell recruitment and tissue infiltration. Pathway enrichment analysis highlighted the involvement of IL-17, IL-26 and TNF signaling pathways in HS pathogenesis. Machine learning identified key markers for diagnostics and therapeutic development. The findings also support the potential for machine learning models to aid in the diagnosis of HS based on immune cell markers. These insights may inform future therapeutic strategies targeting specific immune pathways in HS., Competing Interests: Conflict of Interest WL has received research grant funding from Abbvie, Amgen, Janssen, Leo, Novartis, Pfizer, Regeneron, and TRex Bio. CP has received honoraria and/or travel support from MSD, BMS, Pierre Fabre, MERCK, Sanofi, Almirall, AbbVie, Pelpharma, Amgen, DSD, Takeda, Pfizer, Novartis, Leo, Janssen, Astra Zeneca, and Boehringer Ingelheim. AW received honoraria and travel support from AbbVie, Amgen, Biogen, Janssen, Leo, Novartis, UCB and Sanofi. HN has received grant support from AbbVie; consulting fees from 23andme, Abbvie, Aristea Therapeutics, Nimbus Therapeutics, Medscape, Sonoma Biotherapeutics, DAVA Oncology, Boehringer Ingelheim, Union Chimique Belge’s (UCB) and Novartis; investigator fees from Pfizer; and holds shares in Radera, Inc. She is also an Associate Editor for JAMA Dermatology and Vice President of the Hidradenitis Suppurativa Foundation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Solar energy-driven reduction of CO 2 into fuels with H 2 O as a sacrificial agent is a challenging but desirable subject in photosynthesis. Covalent organic frameworks (COFs) are considered promising candidates for this subject because of their designable structures and functions. The coordination of transition metal ions into COFs is a feasible way to boost the photocatalytic activity. However, postsynthetic modification of COFs with metal ions often leads to a significant decrease in crystallinity and the specific surface area. Herein, we develop a one-pot synthesis of metal-coordinated (nonnoble metal) COFs with high crystallinity. HB-TAPT + Co with ordered and segregated D-A arrays is synthesized by combining 2,4,6-tris(4-aminophenyl)-1,3,5-triazine (TAPT, a strong electron-acceptor) with 2-hydroxy-1,3,5-benzenetricarbaldehyde (HB)-loaded Co 2+ (a strong electron-donor). The CO production when using HB-TAPT + Co under visible light irradiation for 4 h is 78.4 μmol g -1 , which is 3.2 times that of HB-TAPT + Co synthesized by the postsynthetic modification method and 2.65 times that of HB-TAPT without the metal ions. HB-TAPT + Co also has good recycling stability in photocatalytic CO 2 reduction. Additionally, experimental results have demonstrated that the crystallinities of these metal-coordinated materials contribute greatly to the conversion of CO 2 in the photoreaction with H 2 O. This work provides a new protocol for improving the CO 2 photoreduction performance by coordinating metal ions to COFs while maintaining the original crystallinity through a one-pot synthesis method.

Organic solvent nanofiltration (OSN) has become increasingly important in petrochemical and pharmaceutical industries, demanding superior and robust membranes. Herein, we report advanced OSN processes by designing three-dimensional covalent organic framework (3D COF) membranes through moderated interfacial crystallization. Nanoporous supports work as the moderator allowing the crystallization of 3D COF membranes. The 3D COF features sub-nanometer and anti-swelling channels, affording a sharp selectivity to fine targets with an exceptionally high and stable methanol permeance. Thus-synthesized membrane exhibits a record stability against high-concentration feeds and long-term operation for ≈1000 h. Moreover, we unambiguously demonstrate that our membrane holds excellent practicality in purifying active pharmaceutical ingredients from organic liquids. This work reveals the great potential of distinctive 3D COFs in producing prominent OSN membranes for industrial applications., (© 2022 Wiley-VCH GmbH.)

Asymmetric hydrogenation of tetrasubstituted alkenes remains a formidable challenge in asymmetric catalysis. We report herein an unprecedented Rh-catalyzed enantioselective and diastereoselective hydrogenation of easily accessed α,β-disubstituted unsaturated lactams to afford synthetically valuable chiral lactams with 1,2-consecutive stereocenters. The reaction could be performed on the gram scale, and the products could be concisely transformed to enantiomerically pure trans -3,4-disubstituted piperidines, which are prevalent structural units in medicinal agents.