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A controlled growth of two‐dimensional (2D) π‐conjugated metal‐organic frameworks (MOFs) on solid substrates can open exciting opportunities for the application of 2D MOFs as optoelectronic devices. Some factors like solvent composition and type of substrates are known to influence the properties of solution‐processed 2D MOF crystals; however, a mechanistic understanding of how interactions between solvent, substrate, and precursors affect heterogeneous nucleation has been limited. Here, it is reported that the structure of Ni‐catecholate (Ni‐CAT‐1) MOFs at a solid–liquid interface is controlled by solvent–substrate and solvent–MOF precursor interactions. Specifically, the structure of the MOF film can be controlled by varying the affinity of the solvent to the substrate. As a fraction of N,N‐dimethylformamide (DMF) in a binary solvent mixture of water and DMF increases, the arrangement of Ni‐CAT‐1 crystals varies from vertically aligned nanorods to the graphite substrate to less ordered nanorods with the lower initial nucleation number density of Ni‐CAT‐1 crystals on the surface. [ABSTRACT FROM AUTHOR]

Hierarchical nucleation pathways are ubiquitous in the synthesis of minerals and materials. In the case of zeolites and metal–organic frameworks, pre‐organized multi‐ion "secondary building units" (SBUs) have been proposed as fundamental building blocks. However, detailing the progress of multi‐step reaction mechanisms from monomeric species to stable crystals and defining the structures of the SBUs remains an unmet challenge. Combining in situ nuclear magnetic resonance, small‐angle X‐ray scattering, and atomic force microscopy, we show that crystallization of the framework silicate, cyclosilicate hydrate, occurs through an assembly of cubic octameric Q38 polyanions formed through cross‐linking and polymerization of smaller silicate monomers and other oligomers. These Q38 are stabilized by hydrogen bonds with surrounding H2O and tetramethylammonium ions (TMA+). When Q38 levels reach a threshold of ≈32 % of the total silicate species, nucleation occurs. Further growth proceeds through the incorporation of [(TMA)x(Q38)⋅n H2O](x−8) clathrate complexes into step edges on the crystals. [ABSTRACT FROM AUTHOR]

Two‐dimensional (2D) conductive metal‐organic frameworks (MOF) represent a unique class of electrode materials with high capacity and power density. Understanding molecular mechanisms and pathways for heterogeneous nucleation of 2D π‐conjugated MOFs is highly desirable for controlling the structure and properties of conductive MOFs on solid substrates. Herein, a systematic study of nucleation and growth of 2D π‐conjugated Ni‐catecholate (Ni‐CAT‐1) MOFs on highly oriented pyrolytic graphite (HOPG) and copper substrates is reported. It is discovered that the nucleation density and growth kinetics of the MOF film can be controlled by varying substrate interactions with the organic linker. Specifically, π–π interactions between the linker and the HOPG dictate lower nucleation density, whereas π–metal interactions between the linker and the copper substrate dictate faster nucleation and higher nucleation densities. These studies reveal the key mechanism for Ni‐CAT‐1 nucleation on different surfaces and provide insights into interfacial control over the growth of other 2D π‐conjugated MOF films on solid substrates to inform synthesis of functional materials. [ABSTRACT FROM AUTHOR]

Amelogenin constitutes ~90% of the enamel matrix in the secretory stage of amelogenesis, a still poorly understood process that results in the formation of the hardest and most mineralized tissue in vertebrates—enamel. Most biophysical research with amelogenin uses recombinant protein expressed in Escherichia coli. In addition to providing copious amounts of protein, recombinant expression allows 13C‐ and 15N‐labeling for detailed structural studies using NMR spectroscopy. However, native amelogenin is phosphorylated at one position, Ser‐16 in murine amelogenin, and there is mounting evidence that Ser‐16 phosphorylation is important. Using a modified genetic code expansion protocol we have expressed and purified uniformly 13C‐, 15N‐labeled murine amelogenin (pS16M179) with ~95% of the protein being correctly phosphorylated. Homogeneous phosphorylation was achieved using commercially available, enriched, 13C‐, 15N‐labeled media, and protein expression was induced with isopropyl β‐D‐1‐thiogalactopyranoside at 310 K. Phosphoserine incorporation was verified from one‐dimensional 31P NMR spectra, comparison of 1H‐15N HSQC spectra, Phos‐tag SDS PAGE, and mass spectrometry. Phosphorus‐31 NMR spectra for pS16M179 under conditions known to trigger amelogenin self‐assembly into nanospheres confirm nanosphere models with buried N‐termini. Lambda phosphatase treatment of these nanospheres results in the dephosphorylation of pS16M179, confirming that smaller oligomers and monomers with exposed N‐termini are in equilibrium with nanospheres. Such 13C‐, 15N‐labeling of amelogenin with accurately encoded phosphoserine incorporation will accelerate biomineralization research to understand amelogenesis and stimulate the expanded use of genetic code expansion protocols to introduce phosphorylated amino acids into proteins. [ABSTRACT FROM AUTHOR]

While bio‐inspired synthesis offers great potential for controlling nucleation and growth of inorganic particles, precisely tuning biomolecule–particle interactions is a long‐standing challenge. Herein, we used variations in peptoid sequence to manipulate peptoid–Au interactions, leading to the synthesis of concave five‐fold twinned, five‐pointed Au nanostars via a process of repeated particle attachment and facet stabilization. Ex situ and liquid‐phase TEM observations show that a balance between particle attachment biased to occur near the star points, preferential growth along the [100] direction, and stabilization of (111) facets is critical to forming star‐shaped particles. Molecular simulations predict that interaction strengths between peptoids and distinct Au facets differ significantly and thus can alter attachment kinetics and surface energies to form the stars. This work provides new insights into how sequence‐defined ligands affect particle growth to regulate crystal morphology. [ABSTRACT FROM AUTHOR]

The transcription factor forkhead box P3 (FOXP3) is essential for the development of regulatory T cells (Tregs) and their function in immune homeostasis. Previous studies have shown that in natural Tregs (nTregs), FOXP3 can be regulated by polyubiquitination and deubiquitination. However, the molecular players active in this pathway, especially those modulating FOXP3 by deubiquitination in the distinct induced Treg (iTreg) lineage, remain unclear. Here, we identify the ubiquitin‐specific peptidase 44 (USP44) as a novel deubiquitinase for FOXP3. USP44 interacts with and stabilizes FOXP3 by removing K48‐linked ubiquitin modifications. Notably, TGF‐β induces USP44 expression during iTreg differentiation. USP44 co‐operates with USP7 to stabilize and deubiquitinate FOXP3. Tregs genetically lacking USP44 are less effective than their wild‐type counterparts, both in vitro and in multiple in vivo models of inflammatory disease and cancer. These findings suggest that USP44 plays an important role in the post‐translational regulation of Treg function and is thus a potential therapeutic target for tolerance‐breaking anti‐cancer immunotherapy. Synopsis: The ubiquitin‐specific peptidase 44 (USP44) interacts with FOXP3 and stabilizes the transcription factor by removing K48‐linked ubiquitin modifications. USP44 is essential for the establishment of fully functional regulatory T cells. USP44 is a deubiquitinase for FOXP3 and is up‐regulated via TGF‐beta signaling.USP44 cooperates with USP7 to stabilize FOXP3.Tregs with USP44 deficiency are less effective suppressors than wild type controls. [ABSTRACT FROM AUTHOR]

ZIF‐8 was synthesized in supercritical carbon dioxide (scCO2). In situ powder X‐ray diffraction, ex situ microscopy, and simulations provide an encompassing view of the formation of ZIF‐8 and intermediary ZnO@ZIF‐8 composites in this nontraditional solvent. Time‐resolved imaging exposed divergent physicochemical reaction pathways from previous studies of the growth of anisotropic ZIF‐8 core@shell structures in traditional solvents. Synthetically relevant physiochemical properties of scCO2 were integrated into classical nucleation theory, relating interfacial forces, calculated through DFTB+ based molecular dynamics (MD), with 3D nucleation outcomes. The kinetics of crystallization were examined and displayed a characteristic signature of time‐ and temperature‐dependent mechanisms over the extent of the reaction. Lastly, it is shown that subtle factors, such as the extent of reaction and the size/shape of sacrificial templates can tailor ZIF‐8 composition and size, eliciting control over hierarchical porosity in a nonconventional green solvent. [ABSTRACT FROM AUTHOR]

The aim of our study was to assess the associations of HSP90AB1 copy number variations (CNVs) with systemic lupus erythematosus (SLE) risk and glucocorticoids (GCs) efficacy, as well as the relationship between HSP90AB1 single‐nucleotide polymorphisms (SNPs) and GCs efficacy. HSP90AB1 CNVs and SLE risk were analysed in 519 patients and 538 controls. Patients treated with GCs were followed up for 12 weeks and were divided into sensitive and insensitive groups to investigate the effects of CNVs (419 patients) and SNPs (457 patients) on the efficacy of GCs. Health‐related quality of life (HRQoL) was also measured by SF‐36 at baseline and week 12 to explore the relationship between CNVs/SNPs and HRQoL improvements in Chinese SLE patients. Our results indicated a statistically significant association between HSP90AB1 CNVs and SLE (PBH = 0.039), and this association was more pronounced in the female subgroup (PBH = 0.039). However, we did not detect association of HSP90AB1 CNVs/SNPs with efficacy of GCs. But we found a marginal association between SNP rs13296 and improvement in Role‐emotional, while this association was not strong enough to survive in the multiple testing corrections. Collectively, our findings suggest that the copy number of HSP90AB1 is associated with SLE susceptibility. But copy number and polymorphisms of HSP90AB1 may not be associated with efficacy of GCs. [ABSTRACT FROM AUTHOR]

Abstract: Although the rechargeable lithium–oxygen (Li–O2) batteries have extremely high theoretical specific energy, the practical application of these batteries is still limited by the instability of their carbon‐based air‐electrode, Li metal anode, and electrodes, toward reduced oxygen species. Here a simple one‐step in situ electrochemical precharging strategy is demonstrated to generate thin protective films on both carbon nanotubes (CNTs), air‐electrodes and Li metal anodes simultaneously under an inert atmosphere. Li–O2 cells after such pretreatment demonstrate significantly extended cycle life of 110 and 180 cycles under the capacity‐limited protocol of 1000 mA h g−1 and 500 mA h g−1, respectively, which is far more than those without pretreatment. The thin‐films formed from decomposition of electrolyte during in situ electrochemical precharging processes in an inert environment, can protect both CNTs air‐electrode and Li metal anode prior to conventional Li–O2 discharge/charge cycling, where reactive reduced oxygen species are formed. This work provides a new approach for protection of carbon‐based air‐electrodes and Li metal anodes in practical Li–O2 batteries, and may also be applied to other battery systems. [ABSTRACT FROM AUTHOR]

Abstract: The dysregulation of NLRP3 inflammasome can cause uncontrolled inflammation and drive the development of a wide variety of human diseases, but the medications targeting NLRP3 inflammasome are not available in clinic. Here, we show that tranilast (TR), an old anti‐allergic clinical drug, is a direct NLRP3 inhibitor. TR inhibits NLRP3 inflammasome activation in macrophages, but has no effects on AIM2 or NLRC4 inflammasome activation. Mechanismly, TR directly binds to the NACHT domain of NLRP3 and suppresses the assembly of NLRP3 inflammasome by blocking NLRP3 oligomerization. In vivo experiments show that TR has remarkable preventive or therapeutic effects on the mouse models of NLRP3 inflammasome‐related human diseases, including gouty arthritis, cryopyrin‐associated autoinflammatory syndromes, and type 2 diabetes. Furthermore, TR is active ex vivo for synovial fluid mononuclear cells from patients with gout. Thus, our study identifies the old drug TR as a direct NLRP3 inhibitor and provides a potentially practical pharmacological approach for treating NLRP3‐driven diseases. [ABSTRACT FROM AUTHOR]

Crystallization by particle attachment is widely observed in both natural and synthetic environments. Although this form of nonclassical crystallization is generally described by oriented attachment, random aggregation of building blocks to give single-crystal products is also observed, but the mechanism of crystallographic realignment is unknown. We herein reveal that random attachment during aggregation-based growth initially produces a nonoriented growth front. Subsequent evolution of the orientation is driven by the inherent surface stress applied by the disordered surface layer and results in single-crystal formation by grain-boundary migration. This mechanism is corroborated by measurements of orientation rate versus external stress, which demonstrated a predictive relationship between the two. These findings advance our understandings about aggregation-based growth via nanocrystal blocks and suggest an approach to material synthesis that takes advantage of stress-induced coalignment. [ABSTRACT FROM AUTHOR]

Aim The dysfunction of T regulatory cells is important for the pathogenesis of systemic lupus erythematosus ( SLE). Glucocorticoid-induced tumor necrosis factor receptor family-related protein ( GITR) is expressed at low levels on resting responder T lymphocytes (Tresps) and is up-regulated on T regulatory cells (Tregs) and activated T cells, diminishing suppressive activity of Tregs and/or leading to resistance to suppression of Tregs by activated effector T cells. We aimed to explore whether SLE patients had an aberrant expression of GITR on Tregs and responder T cells (Tresps) and the regulation by glucocorticoids. Methods The surface GITR expression on Tregs and Tresps cells were analyzed by flow cytometry in 32 patients and 15 normal controls. Purified Tregs or Tresps were cultured with glucocorticoid. Apoptosis of the cells were determined by the staining of Annexin V. Results Systemic lupus erythematosus patients had higher levels of GITR expressed on CD4+ CD25+, CD4+ CD25high and CD4+ CD25+ CD127low/− Tregs as well as on CD4+ CD25− Tresps compared to healthy controls. The expression of GITR on Tregs and Tresps were positively correlated with score of SLE disease activity index ( SLEDAI). In vitro glucocorticoid induced GITR expression on purified Tresp cells, but not on Tregs, and almost all of the GITR positive cells induced by glucocorticoid encountered apoptosis. Conclusion Aberrant expression of GITR may contribute to SLE pathogenesis. Glucocorticoid may achieve its therapeutic effect partly by inducing GITR expression on Tresps rather than Tregs, which initiates the apoptosis of Tresp cells in SLE patients. [ABSTRACT FROM AUTHOR]

Facet Stabilization, Five-Fold Twinned Au Star, Particle Attachment, Sequence-Defined Peptoids Frontispiz: Peptoid-Directed Formation of Five-Fold Twinned Au Nanostars through Particle Attachment and Facet Stabilization Keywords: Facet Stabilization; Five-Fold Twinned Au Star; Particle Attachment; Sequence-Defined Peptoids EN Facet Stabilization Five-Fold Twinned Au Star Particle Attachment Sequence-Defined Peptoids 1 1 1 03/23/22 20220328 NES 220328 B Nanopartikel b Die peptoiddirigierte Bildung von verzwillingten Au-Nanosternen durch Partikelanlagerung und Facettenstabilisierung wird im Forschungsartikel von James J. DeYoreo, Chun-Long Chen et al. vorgestellt (e202201980). [Extracted from the article]

Regulatory T cells (Tregs) are crucial mediators of immune control. The characteristic gene expression and suppressive functions of Tregs depend considerably on the stable expression and activity of the transcription factor FOXP3. Transcriptional regulation of the Foxp3 gene has been studied in depth, but both the expression and function of this factor are also modulated at the protein level. However, the molecular players involved in posttranslational FOXP3 regulation are just beginning to be elucidated. Here, we found that TRAF6‐deficient Tregs were dysfunctional in vivo; mice with Treg‐restricted deletion of TRAF6 were resistant to implanted tumors and displayed enhanced anti‐tumor immunity. We further determined that FOXP3 undergoes K63‐linked ubiquitination at lysine 262 mediated by the E3 ligase TRAF6. In the absence of TRAF6 activity or upon mutation of the ubiquitination site, FOXP3 displayed aberrant, perinuclear accumulation and disrupted regulatory function. Thus, K63‐linked ubiquitination by TRAF6 ensures proper localization of FOXP3 and facilitates the transcription factor's gene‐regulating activity in Tregs. These results implicate TRAF6 as a key posttranslational, Treg‐stabilizing regulator that may be targeted in novel tolerance‐breaking therapies. Synopsis: Transcription factor FOXP3 is key for development and function of regulatory T cells (Tregs) subject to both transcriptional and posttranscriptional regulation. K63‐linked ubiquitination of FOXP3 by TRAF6 E3 ligase provides a new mechanism to regulate Treg function. Deletion of TRAF6 in Tregs impairs Treg suppressive function and immune homeostasis and anti‐tumour immunity in mice.TRAF6 catalyses K63‐linked ubiquitination of FOXP3 at Lysine 262.The zinc finger and leucine zipper domains of FOXP3 are required for its TRAF6‐mediated ubiquitination.TRAF6‐mediated K63‐ubiquitination promotes nuclear accumulation of FOXP3 and Tregs function. [ABSTRACT FROM AUTHOR]

Die Selbstanordnung von Nanopartikeln ist ein Schlüsselprozess bei der Bildung von Einkristallen durch aggregationsinduziertes Kristallwachstum. Wie R. Tang und Mitarbeiter in ihrer Zuschrift auf S. 13028 ff. mittels hochauflösender Transmissionselektronenmikroskopie nachweisen, aggregieren zunächst Nanopartikel regellos auf der Oberfläche eines vorliegenden Einkristalls. Anschließend drängen Oberflächenkräfte die Kristallkorngrenze vom Kristallinneren an die Oberflächenschicht, um die Anordnung der regellos anhaftenden Nanopartikel zu induzieren, die so schließlich in den Einkristall integriert werden. [ABSTRACT FROM AUTHOR]

Self‐alignment of nanoparticles is a key process in the formation of single crystals through aggregation‐based crystal growth. In their Communication on page 12836 ff., R. Tang and co‐workers demonstrate by using high‐resolution transmission electron microscopy random aggregation of nanoparticles on the surface of a bulk single crystal. Subsequently, surface stress drives the grain boundary to migrate from the crystal bulk to the random surface layer to induce realignment of the randomly attached nanoparticles, which are then integrated into the single crystal. [ABSTRACT FROM AUTHOR]