Solvent-Free Synthesis Enables Encapsulation of Subnanometric FeOx Clusters in Pure Siliceous Zeolites for Efficient Catalytic Oxidation Reactions.

Metal/metal oxide clusters possess a higher count of unsaturated coordination sites than nanoparticles, providing multiatomic sites that single atoms do not. Encapsulating metal/metal oxide clusters within zeolites is a promising approach for synthesizing and stabilizing these clusters. The unique feature endows the metal clusters with an exceptional catalytic performance in a broad range of catalytic reactions. However, the encapsulation of stable FeOx clusters in zeolite is still challenging, which limits the application of zeolite-encapsulated FeOx clusters in catalysis. Herein, we design a modified solvent-free method to encapsulate FeOx clusters in pure siliceous MFI zeolites (Fe@MFI). It is revealed that the 0.3-0.4 nm subnanometric FeOx clusters are stably encapsulated in the 5/6-membered rings intersectional voids of the pure siliceous MFI zeolites. The encapsulated Fe@MFI catalyst with a Fe loading of 1.4 wt % demonstrates remarkable catalytic activity and recycle stability in the direct oxidation of methane, while also promoting the direct oxidation of cyclohexane, surpassing the performance of conventional zeolite-supported Fe catalysts.

The Effectiveness of Indigenous Knowledge-Based Lifestyle Interventions in Preventing Obesity and Type 2 Diabetes Mellitus in Indigenous Children in Canada: A Systematic Review.

Background: Indigenous children in Canada have high rates of obesity and type 2 diabetes mellitus (T2DM). Culturally appropriate interventions, guided by an Indigenous knowledge-based view of health, are crucial to target these conditions. The objective of this systematic review was to assess the impact of indigenous Knowledge-based lifestyle interventions on the prevention of obesity and T2DM in Indigenous children in Canada. Methods: Database searches were conducted from inception until February 22, 2022. The main outcomes were changes in Body Mass Index (BMI) z-score and the development of T2DM. The other outcomes included adiposity, metabolic, and lifestyle determinants of health. The GRADE approach was used to assess confidence in the evidence. Results: Four non-randomized controlled trials (non-RCTs) and six uncontrolled studies were identified. Peer-led interventions led to a reduction in BMI z-score and waist circumference. GRADE assessment revealed very low quality of evidence due to a lack of randomization and small sample sizes. There were no diabetes-specific reported programs. Conclusion: Limited evidence from non-randomized studies suggest that peer-led indigenous Knowledge-based lifestyle interventions improve BMI z-score and central adiposity. There is a need for community-owned and adequately powered randomized studies for interventions that aim to treat and prevent obesity and T2DM in Indigenous children in Canada. Systematic Review Registration: PROSPERO CRD42017072781.

Barriers and Facilitators to Delivering Inpatient Cardiac Rehabilitation: A Scoping Review.

Objective: The purpose of this scoping review was to summarize the literature on barriers and facilitators that influence the provision and uptake of inpatient cardiac rehabilitation (ICR). Methods: A literature search was conducted using PsycINFO, MEDLINE, EMBASE, CINAHL and AgeLine. Studies were included if they were published in English after the year 2000 and focused on adults who were receiving some form of ICR (eg, exercise counselling and training, education for heart-healthy living). For studies meeting inclusion criteria, descriptive data on authors, year, study design, and intervention type were extracted. Results: The literature search resulted in a total of 44,331 publications, of which 229 studies met inclusion criteria. ICR programs vary drastically and often focus on promoting physical exercises and patient education. Barriers and facilitators were categorized through patient, provider and system level factors. Individual characteristics and provider knowledge and efficacy were categorized as both barriers and facilitators to ICR delivery and uptake. Team functioning, lack of resources, program coordination, and inconsistencies in evaluation acted as key barriers to ICR delivery and uptake. Key facilitators that influence ICR implementation and engagement include accreditation and professional associations and patient and family-centred practices. Conclusion: ICR programs can be highly effective at improving health outcomes for those living with CVDs. Our review identified several patient, provider, and system-level considerations that act as barriers and facilitators to ICR delivery and uptake. Future research should explore how to encourage health promotion knowledge amongst ICR staff and patients.

Unique (100) Surface Configuration Enables Promising Oxygen Reduction Performance for Pt3Co Nanodendrite Catalysts.

Selective exposure of active surfaces of Pt-based electrocatalysts has been demonstrated as an effective strategy to improve Pt utilization and promote oxygen reduction reaction (ORR) activity in fuel cell application. However, challenges remain in stabilizing those active surface structures, which often suffer undesirable degradation and poor durability along with surface passivation, metal dissolution, and agglomeration of Pt-based electrocatalysts. To overcome the aforementioned obstacles, we here demonstrate the unique (100) surface configuration enabling active and stable ORR performance for bimetallic Pt3Co nanodendrite structures. Using elaborate microscopy and spectroscopy characterization, it is revealed that the Co atoms are preferentially segregated and oxidized at the Pt3Co(100) surface. In situ X-ray absorption spectroscopy (XAS) shows that such (100) surface configuration prevents the oxygen chemisorption and oxide formation on active Pt during the ORR process. Thus, the Pt3Co nanodendrite catalyst shows not only a high ORR mass activity of 730 mA/mg at 0.9 V vs RHE, which is 6.6-fold higher than that of the Pt/C, but also impressively high stability with 98% current retention after the acceleration degradation test in acid media for 5000 cycles, far exceeding the Pt or Pt3Co nanoparticles. Density functional theory (DFT) calculation also confirms the lateral and structural effects from the segregated Co and oxides on the Pt3Co(100) surface in reducing the catalyst oxophilicity and the free energy for the formation of an OH intermediate in the ORR.

Probing the Roles of Indium Oxides on Copper Catalysts for Enhanced Selectivity during CO2-to-CO Electrochemical Reduction.

The electrochemical CO2 reduction reaction (CO2RR) provides an alternative protocol to producing industrial chemicals with renewable electricity sources, and the highly selective, durable, and economic catalysts should expedite CO2RR applications. Here, we demonstrate a composite Cu-In2O3 catalyst in which a trace amount of In2O3 decorated on Cu surface greatly improves the selectivity and stability for CO2-to-CO reduction as compared to the counterparts (Cu or In2O3), realizing a CO faradaic efficiency (FECO) of 95% at -0.7 V (vs RHE) and no obvious degradation within 7 h. In situ X-ray absorption spectroscopy reveals that In2O3 undergoes the redox reaction and preserves the metallic state of Cu during the CO2RR process. Strong electronic interaction and coupling occur at the Cu/In2O3 interface which serves as the active site for selective CO2RR. Theoretical calculation confirms the roles of In2O3 in preventing oxidation and altering the electronic structure of Cu to assist COOH* formation and demote CO* adsorption at the Cu/In2O3 interface.

Pt-Mediated Interface Engineering Boosts the Oxygen Reduction Reaction Performance of Ni Hydroxide-Supported Pd Nanoparticles.

Fuel cells are considered potential energy conversion devices for utopia; nevertheless, finding a highly efficacious and economical electrocatalyst for the oxygen reduction reaction (ORR) is of great interest. By keeping this in view, we have proposed a novel design of a trimetallic nanocatalyst (NC) comprising atomic Pt clusters at the heterogeneous Ni(OH)2-to-Pd interface (denoted NPP-70). The as-prepared material surpasses the commercial J.M.-Pt/C (20 wt %) catalyst by ∼ 166 and ∼19 times with exceptionally high specific and mass activities of 16.11 mA cm-2 and 484.8 mA mgPt-1 at 0.90 V versus reversible hydrogen electrode (RHE) in alkaline ORR (0.1 M KOH), respectively. On top of that, NPP-70 NC retains nearly 100% performance after 10k accelerated durability test (ADT) cycles. The results of physical characterization and electrochemical analysis confirm that atomic-scale Pt clusters induce strong lattice strain (compressive) at the Ni(OH)2-to-Pd interface, which triggers the electron relocation from Ni to Pt atoms. Such charge localization is vital for O2 splitting on surface Pt atoms, followed by the relocation of OH- ions from the Pd surface. Besides, a sharp fall down in ORR performance (mass activity is 37 mA mgPt-1 at 0.90 V versus RHE) is observed when the Pt clusters are decorated on the surface of NiOx and Pd (denoted NPP-RT). In situ partial fluorescence yield mode X-ray absorption spectroscopy (PFY-XAS) was employed to reveal the ORR pathways on both configurations. The obtained results demonstrate that interface engineering can be a potential approach to boost the electrocatalytic activity of metal hydroxide/oxide-supported Pd nanoparticles and in turn allow Pd to be a promising alternative for commercial Pt catalysts.

Ultrastable Fe-N-C Fuel Cell Electrocatalysts by Eliminating Non-Coordinating Nitrogen and Regulating Coordination Structures at High Temperatures.

Pyrolyzed Fe-N-C materials have attracted considerable interest as one of the most active noble-metal-free electrocatalysts for the oxygen reduction reaction (ORR) in proton exchange membrane fuel cells (PEMFCs). Despite significant progress is made in improving their catalytic activity during past decades, the Fe-N-C catalysts still suffer from fairly poor electrochemical and storage stability, which greatly hurdles their practical application. Here, an effective strategy is developed to greatly improve their catalytic stability in PEMFCs and storage stability by virtue of previously unexplored high-temperature synthetic chemistry between 1100 and 1200 °C. Pyrolysis at this rarely adopted temperature range not only enables the elimination of less active nitrogen-doped carbon sites that generate detrimental peroxide byproduct but also regulates the coordination structure of Fe-N-C from less stable D1 (O-FeN4 C12 ) to a more stable D2 structure (FeN4 C10 ). The optimized Fe-N-C catalyst exhibits excellent stability in PEMFCs (>80% performance retention after 30 h under H2 /O2 condition) and no activity loss after 35 day storage while maintaining a competitive ORR activity and PEMFC performance.

Co-Existence of Atomic Pt and CoPt Nanoclusters on Co/SnOx Mix-Oxide Demonstrates an Ultra-High-Performance Oxygen Reduction Reaction Activity.

An effective approach for increasing the Noble metal-utilization by decorating the atomic Pt clusters (1 wt.%) on the CoO2@SnPd2 nanoparticle (denoted as CSPP) for oxygen reduction reaction (ORR) is demonstrated in this study. For the optimum case when the impregnation temperature for Co-crystal growth is 50 °C (denoted as CSPP-50), the CoPt nanoalloys and Pt-clusters decoration with multiple metal-to-metal oxide interfaces are formed. Such a nanocatalyst (NC) outperforms the commercial Johnson Matthey-Pt/C (J.M.-Pt/C; 20 wt.% Pt) catalyst by 78-folds with an outstanding mass activity (MA) of 4330 mA mgPt-1 at 0.85 V vs. RHE in an alkaline medium (0.1 M KOH). The results of physical structure inspections along with electrochemical analysis suggest that such a remarkable ORR performance is dominated by the potential synergism between the surface anchored Pt-clusters, CoPt-nanoalloys, and adjacent SnPd2 domain, where Pt-clusters offer ideal adsorption energy for O2 splitting and CoPt-nanoalloys along with SnPd2 domain boost the subsequent desorption of hydroxide ions (OH-).

The production technology of mineral soda alumina glass: A perspective from microstructural analysis of glass beads in Iron Age Taiwan.

Mineral soda alumina (m-Na-Al) glass is a common glass production group found around the Indo-Pacific region. In Iron Age Taiwan, its presence dates back to the early 1st millennium AD. This research discusses m-Na-Al glass beads excavated from Iron Age sites in Taiwan. No production sites for m-Na-Al have been found, but microstructural analysis suggests m-Na-Al glass appears to originate around South Asia and is exchanged widely. SEM-EDS and EPMA were used to analyse red, orange, yellow, green and blue m-Na-Al glass. The microstructure of the glass shows the presence of plagioclase and alkali feldspar relics in the glass, suggesting a low manufacturing temperature. Copper-based colourants are identified in red, orange, blue and green glass, while lead tin oxide is used in yellow and green glass. It appears that various types of copper-containing raw materials were procured by craftspeople, and a self-reduction process for producing red and orange glass is tentatively proposed. Additionally, the microstructure of yellow glass reveals different colouring paths were used. These results increase our understanding of the selection of raw materials, and provide an impetus for further research on the cross craft interaction between glass and copper production.

Stable Pd-Cu Hydride Catalyst for Efficient Hydrogen Evolution.

Pd has been regarded as one of the alternatives to Pt as a promising hydrogen evolution reaction (HER) catalyst. Strategies including Pd-metal alloys (Pd-M) and Pd hydrides (PdHx) have been proposed to boost HER performances. However, the stability issues, e.g., the dissolution in Pd-M and the hydrogen releasing in PdHx, restrict the industrial application of Pd-based HER catalysts. We here design and synthesize a stable Pd-Cu hydride (PdCu0.2H0.43) catalyst, combining the advantages of both Pd-M and PdHx structures and improving the HER durability simultaneously. The hydrogen intercalation is realized under atmospheric pressure (1.0 atm) following our synthetic approach that imparts high stability to the Pd-Cu hydride structure. The obtained PdCu0.2H0.43 catalyst exhibits a small overpotential of 28 mV at 10 mA/cm2, a low Tafel slope of 23 mV/dec, and excellent HER durability due to its appropriate hydrogen adsorption free energy and alleviated metal dissolution rate.

Enhanced CO2 Electrochemical Reduction Performance over Cu@AuCu Catalysts at High Noble Metal Utilization Efficiency.

The electrochemical CO2 reduction reaction (CO2RR) represents a viable alternative to help close the anthropogenic carbon cycle and convert intermittent electricity from renewable energy sources to chemical energy in the form of value-added chemicals. The development of economic catalysts possessing high faradaic efficiency (FE) and mass activity (MA) toward CO2RR is critical in accelerating CO2 utilization technology. Herein, an elaborate Au-Cu catalyst where an alloyed AuCu shell caps on a Cu core (Cu@AuCu) is developed and evaluated for CO2-to-CO electrochemical conversion. Specific roles of Cu and Au for CO2RR are revealed in the alloyed core-shell structure, respectively, and a compositional-dependent volcano-plot is disclosed for the Cu@AuCu catalysts toward selective CO production. As a result, the Au2-Cu8 alloyed core-shell catalyst (only 17% Au content) achieves an FECO value as high as 94% and an MACO of 439 mA/mgAu at -0.8 V (vs RHE), superior to the values for pure Au, reflecting its high noble metal utilization efficiency.

Tri-atomic Pt clusters induce effective pathways in a Cocore-Pdshell nanocatalyst surface for a high-performance oxygen reduction reaction.

The crux of the hot topic concerning the widespread replacement of fuel cells (FCs) with traditional petrochemical energy is to balance improving the oxygen reduction reaction (ORR) and reducing the cost. The present study employs density functional theory (DFT) to investigate the effect of Pt ensemble size regulation from a single atom to full coverage on the physio-chemical properties, oxygen adsorption energies and overall ORR efficiency of bimetallic nanocatalysts (NCs) with a Cocore-Pdshell structure. Our results reveal that the electronegativity difference and lattice strain between neighboring heteroatoms are enhanced to trigger a synergetic effect in local domains, with the Pt cluster size reduced from nanometers to subnanometers. They induce a directed and tunable charge relocation mechanism from deep Co to topmost Pt to optimize the adsorption energies of O2/O* and achieve excellent ORR kinetics performance with minimum Pt usage but maximum Pt atom utilization (i.e., Pt1 to Pt3) compared with benchmark Pt(111). Such a dependency between the cluster size and corresponding ORR performance for the established Co@Pd-Ptn system can be applied to accurately guide the experimental synthesis of ordered heterogeneous catalysts (e.g., other core@shell-clusters structures) toward low Pt, high efficiency and green economy.

Thousands of induced germline mutations affecting immune cells identified by automated meiotic mapping coupled with machine learning.

Forward genetic studies use meiotic mapping to adduce evidence that a particular mutation, normally induced by a germline mutagen, is causative of a particular phenotype. Particularly in small pedigrees, cosegregation of multiple mutations, occasional unawareness of mutations, and paucity of homozygotes may lead to erroneous declarations of cause and effect. We sought to improve the identification of mutations causing immune phenotypes in mice by creating Candidate Explorer (CE), a machine-learning software program that integrates 67 features of genetic mapping data into a single numeric score, mathematically convertible to the probability of verification of any putative mutation-phenotype association. At this time, CE has evaluated putative mutation-phenotype associations arising from screening damaging mutations in ∼55% of mouse genes for effects on flow cytometry measurements of immune cells in the blood. CE has therefore identified more than half of genes within which mutations can be causative of flow cytometric phenovariation in Mus musculus The majority of these genes were not previously known to support immune function or homeostasis. Mouse geneticists will find CE data informative in identifying causative mutations within quantitative trait loci, while clinical geneticists may use CE to help connect causative variants with rare heritable diseases of immunity, even in the absence of linkage information. CE displays integrated mutation, phenotype, and linkage data, and is freely available for query online.

SLFN2 protection of tRNAs from stress-induced cleavage is essential for T cell-mediated immunity.

Reactive oxygen species (ROS) increase in activated T cells because of metabolic activity induced to support T cell proliferation and differentiation. We show that these ROS trigger an oxidative stress response that leads to translation repression. This response is countered by Schlafen 2 (SLFN2), which directly binds transfer RNAs (tRNAs) to protect them from cleavage by the ribonuclease angiogenin. T cell-specific SLFN2 deficiency results in the accumulation of tRNA fragments, which inhibit translation and promote stress-granule formation. Interleukin-2 receptor ß (IL-2Rß) and IL-2Rγ fail to be translationally up-regulated after T cell receptor stimulation, rendering SLFN2-deficient T cells insensitive to interleukin-2's mitogenic effects. SLFN2 confers resistance against the ROS-mediated translation-inhibitory effects of oxidative stress normally induced by T cell activation, permitting the robust protein synthesis necessary for T cell expansion and immunity.

Dominant atopy risk mutations identified by mouse forward genetic analysis.

BACKGROUND: Atopy, the overall tendency to become sensitized to an allergen, is heritable but seldom ascribed to mutations within specific genes. Atopic individuals develop abnormally elevated IgE responses to immunization with potential allergens. To gain insight into the genetic causes of atopy, we carried out a forward genetic screen for atopy in mice. METHODS: We screened mice carrying homozygous and heterozygous N-ethyl-N-nitrosourea (ENU)-induced germline mutations for aberrant antigen-specific IgE and IgG1 production in response to immunization with the model allergen papain. Candidate genes were validated by independent gene mutation. RESULTS: Of 31 candidate genes selected for investigation, the effects of mutations in 23 genes on papain-specific IgE or IgG1 were verified. Among the 20 verified genes influencing the IgE response, eight were necessary for the response, while 12 repressed IgE. Nine genes were not previously implicated in the IgE response. Fifteen genes encoded proteins contributing to IgE class switch recombination or B-cell receptor signaling. The precise roles of the five remaining genes (Flcn, Map1lc3b, Me2, Prkd2, and Scarb2) remain to be determined. Loss-of-function mutations in nine of the 12 genes limiting the IgE response were dominant or semi-dominant for the IgE phenotype but did not cause immunodeficiency in the heterozygous state. Using damaging allele frequencies for the corresponding human genes and in silico simulations (Monte Carlo) of undiscovered atopy mutations, we estimated the percentage of humans with heterozygous atopy risk mutations. CONCLUSIONS: Up to 37% of individuals may be heterozygous carriers for at least one dominant atopy risk mutation.

CO-Reductive and O2-Oxidative Annealing Assisted Surface Restructure and Corresponding Formic Acid Oxidation Performance of PdPt and PdRuPt Nanocatalysts.

Formic acid oxidation reaction (FAOR) at anode counterpart incurs at substantial high overpotential, limiting the power output efficiency of direct formic acid fuel cells (DFAFCs). Despite intense research, the lack of high-performance nanocatalysts (NCs) for FAOR remains a challenge in realizing DFAFC technologies. To surmount the overpotential losses, it is desirable to have NCs to trigger the FAOR as close to the reversible conditions (i.e. with over-potential loss as close to zero as possible). Herein, Pd-based binary and ternary NCs consisting of PdPt and PdRuPt have been synthesized via the polyol reduction method on the carbon support. As prepared PdPt and PdRuPt NCs were further subjected to heat treatment (annealed) in CO (namely PdPt-CO and PdRuPt-CO) and O2 (namely PdPt-O2 and PdRuPt-O2) atmosphere at 473 K temperature. By cross-referencing results of electron microscopy and X-ray spectroscopy together with electrochemical analysis, the effects of heat treatment under CO-reductive and O2-oxidative conditions towards FAOR were schematically elucidated. Of special relevance, the mass activity (MA) of PdPt-CO, PdPt-O2, PdRuPt-CO, and PdRuPt-O2 NCs is 1.7/2.0, 1.3/2.2, 1.1/5.5, and 0.9/4.7 Amg-1 in the anodic/cathodic scan, respectively, which is 2~4-folds improved comparative to of as-prepared PdPt (1.0/1.9 Amg-1 in anodic/cathodic scan, respectively) and PdRuPt (0.9/1.4 Amg-1 in anodic/cathodic scan, respectively) NCs. Meanwhile, after chronoamperometric (CA) stability test up to 2000 s, PdPt-CO (72 mAmg-1) and PdRuPt-CO (213 mAmg-1) NCs exhibit higher MA compared to as-prepared PdPt (54 mAmg-1) and PdRuPt (62 mAmg-1) NCs, which is attributed to the increase of surface Pt composition, especially for PdRuPt-CO NC. Besides, the stability of PdPt-O2 (15 mAmg-1) and PdRuPt-O2 (22 mAmg-1) NCs is deteriorated as compared to that of as-prepared NCs due to severe oxidation in O2 atmosphere. Of utmost importance, we developed a ternary PdRuPt catalyst with ultra-low Pt content (~2 wt.%) and significantly improved FAOR performance than pure Pt catalysts. Moreover, we demonstrated that the FAOR performance can be further enhanced by more than 30% via a unique CO annealing treatment.

High Durability of Pt3Sn/Graphene Electrocatalysts toward the Oxygen Reduction Reaction Studied with In Situ QEXAFS.

To prevent the corrosion of carbon and to enhance corrosion resistance, charge transfer, and mass transfer, graphene, which exhibits a high surface area and good conductivity, was used as an electrocatalyst support for a fuel cell. Pt3Sn/G electrocatalysts for the oxygen reduction reaction (ORR) were prepared with alcohol reduction. The characterization of synthesized catalysts was analyzed according to the energy-dispersive spectrometer (EDS), X-ray diffraction (XRD), high-resolution transmission electron microscope (HRTEM), and extended X-ray absorption fine structure (EXAFS). The electrochemical performance was analyzed with cyclic-voltammetry (CV), linear sweep voltammetry (LSV), and accelerated degradation test (ADT) measurements. The Pt3Sn/G electrocatalysts showed more positive onset potential and larger ORR mass activity than commercial Pt/C catalysts after 5000 cycles of ADT, indicating that in an acidic environment, Pt3Sn/G is more chemically stable than Pt/C. Graphene has effective acid tolerance, is more stable against corrosion, and shows increased stability through preventing PtSn nanoparticles from detaching from the surface. According to the in situ quick EXAFS (QEXAFS) under a CV test to clarify the potential-dependent state of the Pt3Sn/G electrocatalyst, the results show that the electrode surface is reproducible; there is no perceptible change in the oxidation state of the Pt3Sn/G electrocatalyst. The radial distribution function (RDF) of the EXAFS spectra shows that the adsorption and desorption of H+ and OH- cause no structural change in the Pt3Sn crystallites. This work provides insight into the reaction mechanism of proton electroreduction and hydrogen adsorption on a Pt3Sn/G electrocatalyst surface.

Optimization of Pt-Oxygen-Containing Species Anodes for Ethanol Oxidation Reaction: High Performance of Pt-AuSnOx Electrocatalyst.

Pt-oxygen-containing species (Pt-OCS) catalysts, in which OCS (e.g., metal-oxides) are decorated on a Pt surface, possess enhanced ethanol oxidation reaction (EOR) activity and stability compared with pure Pt and are promising in practical applications of direct ethanol fuel cells. We investigate the promotion roles of Pt-OCS electrocatalysts toward the EOR via a combination of density functional theory (DFT) calculations and experiments, providing a rational design strategy for Pt-OCS catalysts. It is revealed that Pt-AuO and Pt-SnO excel in EOR activity and stability, respectively, among the DFT screening of various Pt-OCS systems, and this is confirmed by the following experiments. Moreover, an optimized Pt-AuSnO catalyst is proposed by DFT calculations, taking advantage of both Pt-AuO and Pt-SnO. The as-prepared Pt-AuSnO catalyst delivers an EOR activity that is 9.7 times higher than that of Pt and shows desired stability. These findings are expected to elucidate the mechanistic insights into Pt-OCS materials and lead to advanced EOR electrocatalysts.

Mutual inhibition between Prkd2 and Bcl6 controls T follicular helper cell differentiation.

T follicular helper cells (TFH) participate in germinal center (GC) development and are necessary for B cell production of high-affinity, isotype-switched antibodies. In a forward genetic screen, we identified a missense mutation in Prkd2, encoding the serine/threonine kinase protein kinase D2, which caused elevated titers of immunoglobulin E (IgE) in the serum. Subsequent analysis of serum antibodies in mice with a targeted null mutation of Prkd2 demonstrated polyclonal hypergammaglobulinemia of IgE, IgG1, and IgA isotypes, which was exacerbated by the T cell-dependent humoral response to immunization. GC formation and GC B cells were increased in Prkd2-/- spleens. These effects were the result of excessive cell-autonomous TFH development caused by unrestricted Bcl6 nuclear translocation in Prkd2-/- CD4+ T cells. Prkd2 directly binds to Bcl6, and Prkd2-dependent phosphorylation of Bcl6 is necessary to constrain Bcl6 to the cytoplasm, thereby limiting TFH development. In response to immunization, Bcl6 repressed Prkd2 expression in CD4+ T cells, thereby committing them to TFH development. Thus, Prkd2 and Bcl6 form a mutually inhibitory positive feedback loop that controls the stable transition from naïve CD4+ T cells to TFH during the adaptive immune response.

Bariatric interventions in obesity treatment and prevention in pediatric acute lymphoblastic leukemia: a systematic review and meta-analysis.

Most children are surviving acute lymphoblastic leukemia (ALL) today. Yet, the emergence of cardiometabolic comorbidities in this population may impact long-term outcomes including the quality of life and lifespan. Obesity is a major driver of cardiometabolic disorders in the general population, and in ALL patients it is associated with increased risk of hypertension, dysglycemia, and febrile neutropenia when compared with lean ALL patients undergoing therapy. This systematic review aims to assess the current evidence for bariatric interventions to manage obesity in children with ALL. The primary outcome for this systematic review was the change in BMI z-score with implementation of the interventions studied. Literature searches were conducted in several databases. Ten publications addressing the study question were included in this review, and five studies were used in the meta-analysis to assess the impact of the bariatric interventions on obesity. The BMI z-score did not change significantly with the interventions. However, the quality of evidence was low, which precluded the recommendation of their use. In conclusion, prospective, rigorous, adequately powered, and high-quality longitudinal studies are urgently needed to deliver effective lifestyle interventions to children with ALL to treat and prevent obesity. These interventions, if successful, may improves cardiometabolic health outcomes and enhance the quality of life and life expectancy in children with ALL.