A randomized double-blinded trial to assess recurrence of systemic allergic reactions following COVID-19 mRNA vaccination.

BACKGROUND: Systemic allergic reactions (sARs) following coronavirus disease 2019 (COVID-19) mRNA vaccines were initially reported at a higher rate than after traditional vaccines. OBJECTIVE: We aimed to evaluate the safety of revaccination in these individuals and to interrogate mechanisms underlying these reactions. METHODS: In this randomized, double-blinded, phase 2 trial, participants aged 16 to 69 years who previously reported a convincing sAR to their first dose of COVID-19 mRNA vaccine were randomly assigned to receive a second dose of BNT162b2 (Comirnaty) vaccine and placebo on consecutive days in a blinded, 1:1 crossover fashion at the National Institutes of Health. An open-label BNT162b2 booster was offered 5 months later if the second dose did not result in severe sAR. None of the participants received the mRNA-1273 (Spikevax) vaccine during the study. The primary end point was recurrence of sAR following second dose and booster vaccination; exploratory end points included biomarker measurements. RESULTS: Of 111 screened participants, 18 were randomly assigned to receive study interventions. Eight received BNT162b2 second dose followed by placebo; 8 received placebo followed by BNT162b2 second dose; 2 withdrew before receiving any study intervention. All 16 participants received the booster dose. Following second dose and booster vaccination, sARs recurred in 2 participants (12.5%; 95% CI, 1.6 to 38.3). No sAR occurred after placebo. An anaphylaxis mimic, immunization stress-related response (ISRR), occurred more commonly than sARs following both vaccine and placebo and was associated with higher predose anxiety scores, paresthesias, and distinct vital sign and biomarker changes. CONCLUSIONS: Our findings support revaccination of individuals who report sARs to COVID-19 mRNA vaccines. Distinct clinical and laboratory features may distinguish sARs from ISRRs.

Carbazole-based artificial light-harvesting system for photocatalytic cross-coupling dehydrogenation reaction.

A carbazole-based artificial light-harvesting system (LHS) was successfully fabricated based on the supramolecular assembly of AIE-enhanced donor (CTD), water-soluble phosphate-pillar[5]arene (WPP5), and eosin Y (ESY) acceptor. The formed WPP5-CTD possessed remarkable AIE emission, featuring an ideal energy donor for light harvesting. After encapsulation of ESY, the energy of WPP5-CTD was efficiently transferred to ESY in WPP5-CTD-ESY, and the antenna effect was 38.5, which was much higher than that of recently reported LHSs. Notably, WPP5-CTD-ESY was successfully utilized as a photocatalyst to realize the cross-coupling dehydrogenation reaction of diphenylphosphine oxide and benzothiazole derivatives, suggesting great potential for aqueous photocatalytic applications of this LHS.

PLCG2-associated immune dysregulation (PLAID) comprises broad and distinct clinical presentations related to functional classes of genetic variants.

BACKGROUND: Pathogenic variants of phospholipase C gamma 2 (PLCG2) cause 2 related forms of autosomal-dominant immune dysregulation (ID), PLCγ2-associated antibody deficiency and immune dysregulation (PLAID) and autoinflammatory PLAID (APLAID). Since describing these conditions, many PLCG2 variants of uncertain significance have been identified by clinical sequencing of patients with diverse features of ID. OBJECTIVE: We sought to functionally classify PLCG2 variants and explore known and novel genotype-function-phenotype relationships. METHODS: Clinical data from patients with PLCG2 variants were obtained via standardized questionnaire. PLCG2 variants were generated by mutagenesis of enhanced green fluorescent protein (EGFP)-PLCG2 plasmid, which was overexpressed in Plcg2-deficient DT-40 B cells. B-cell receptor-induced calcium flux and extracellular signal-regulated kinase phosphorylation were assayed by flow cytometry. In some cases, stimulation-induced calcium flux was also measured in primary patient cells. RESULTS: Three-fourths of PLCG2 variants produced functional alteration of B-cell activation, in vitro. Thirteen variants led to gain of function (GOF); however, most functional variants defined a new class of PLCG2 mutation, monoallelic loss of function (LOF). Susceptibility to infection and autoinflammation were common with both GOF and LOF variants, whereas a new phenotypic cluster consisting of humoral immune deficiency, autoinflammation, susceptibility to herpesvirus infection, and natural killer cell dysfunction was observed in association with multiple heterozygous LOF variants detected in both familial and sporadic cases. In some cases, PLCG2 variants produced greater effects in natural killer cells than in B cells. CONCLUSIONS: This work expands the genotypic and phenotypic associations with functional variation in PLCG2, including a novel form of ID in carriers of heterozygous loss of PLCG2 function. It also demonstrates the need for more diverse assays for assessing the impact of PLCG2 variants on human disease.

LIM and Cysteine-Rich Domains 1 Promotes Transforming Growth Factor ß1-Induced Epithelial-Mesenchymal Transition in Human Kidney 2 Cells.

Renal fibrosis is the major pathologic manifestation of chronic kidney disease (CKD). LIM and cysteine-rich domains 1 (LMCD1) is upregulated in the kidney tissue from patients with CKD and the transforming growth factor ß1 (TGF-ß1)-treated human renal tubular epithelial cell line human kidney 2 (HK-2) (Gene Expression Omnibus: GSE66494 and GSE23338). Previously, we have demonstrated that the knockdown of LMCD1 ameliorated renal fibrosis in mice by blocking the activation of the extracellular signal-regulated kinase pathway. In this study, we sought to further investigate whether LMCD1 affects TGF-ß1-induced epithelial-mesenchymal transition (EMT) of kidney tubular epithelial cells and its potential role in the TGF-ß1/Smad signaling pathway. First, we confirmed that LMCD1 expression was increased in the fibrotic kidneys of patients with CKD compared with that in normal kidneys and that LMCD1 was predominantly localized in the renal tubules. LMCD1 and mesenchymal markers were upregulated in obstructed kidney tissues of mice at 21 days after unilateral ureteral obstruction surgery compared with the tissues in sham mice. Next, we demonstrated that TGF-ß1 significantly increased LMCD1 expression through Smad-mediated transcription in HK-2 cells in vitro. In turn, LMCD1 acted as a transcriptional coactivator of E2F transcription factor 1 to promote the transcription of TGF-ß1. Moreover, TGF-ß1 increased the interaction between LMCD1 and Smad ubiquitination regulatory factor 2 (Smurf2) and accelerated Smurf2-mediated LMCD1 degradation via the ubiquitination system. The knockdown of LMCD1 inhibited TGF-ß1-induced EMT in both HK-2 cells and unilateral ureteral obstruction mice. Our results indicate a positive feedback loop between TGF-ß1 and LMCD1 for EMT induction in HK-2 cells and that Smurf2 acts as a negative regulator in this process by accelerating LMCD1 degradation.

Multifunctional anthraquinone-sulfonic potassium salts passivate the buried interface for efficient and stable planar perovskite solar cells.

SnO2-based planar perovskite solar cells (PSCs) are considered as potential photovoltaic candidates due to their simple structures and cost-effective preparation processes. However, the extensive defects accumulated at the buried interface between perovskite and SnO2 greatly hinder the further improvement of PSC efficiency and stability. Herein, the potassium salt of anthraquinone-1,8-disulfonate (ASPS) is used as a novel multifunctional interfacial modifier to improve the carrier transport performance at the buried interface and optimize the quality of the upper perovskite light absorber layer (PVK) in PSCs. Owing to the synergistic effect of sulfonic acid groups, carbonyl groups and potassium ions in ASPS, the accumulated defects at the buried interface are passivated, the energy level arrangement of the interface is optimized, and the crystalline quality and optoelectronic properties of the PVK films are improved. As a result, the power conversion efficiency (PCE) improved significantly from 21.36% for the controlled device to 23.96% for the ASPS-modified device. Furthermore, the unencapsulated ASPS-modified device also exhibited better storage stability and thermal stability than the controlled device.

High-Efficiency CsPbI2Br Perovskite Solar Cells with over 83% Fill Factor by Synergistic Effects of a Multifunctional Additive.

All-inorganic CsPbI2Br with outstanding thermal stability and excellent photoelectric properties is considered as a promising candidate for photovoltaic applications. However, the efficiency of CsPbI2Br perovskite solar cells (PSCs) is still much lower than that of their organic-inorganic hybrid counterparts or CsPbI3-based devices. Herein, we obtained an optimized CsPbI2Br PSC (0.09 cm2) with a champion efficiency of 17.38% and a record fill factor of 83.6% by introducing potassium anthraquinone-1,8-disulfonate (DAD) in the precursor solution. The synergistic effect between the electronegative functional groups and K+ ions in the DAD structure can not only effectively regulate the crystallization growth process to improve the crystalline quality and stability of photo-active CsPbI2Br but also optimize the energy level alignment and passivate the defects to improve the carrier transport properties. The efficiency of the corresponding large-area device (5 cm × 5 cm with an active area of 19.25 cm2) reached 13.20%. Moreover, the optimized CsPbI2Br PSC exhibited negligible hysteresis and enhanced long-term storage stability as well as thermal stability. Our method produces more stable photo-active CsPbI2Br with excellent photoelectric properties for industrial applications or perovskite/silicon tandem cells.

Water-soluble phosphate-pillar[5]arene (WPP5)-based artificial light-harvesting system for photocatalytic cross-coupling dehydrogenation.

A novel water-soluble phosphate-pillar[5]arene (WPP5)-based artificial light-harvesting system (LHS) was successfully fabricated through the supramolecular assembly of phenyl-pyridyl-acrylonitrile derivative (PBT), WPP5, and organic pigment Eosin Y (ESY). Initially, after host-guest interaction, WPP5 could bind well with PBT and form WPP5 âŠƒ PBT complexes in water, which further assembled into WPP5 âŠƒ PBT nanoparticles. WPP5 âŠƒ PBT nanoparticles performed an outstanding aggregation-induced emission (AIE) capability because of the J-aggregates of PBT in WPP5 âŠƒ PBT nanoparticles, which were appropriate as fluorescence resonance energy transfer (FRET) donors for artificial light-harvesting. Moreover, due to the emission region of WPP5 âŠƒ PBT overlapped well with the UV-Vis absorption of ESY, the energy of WPP5 âŠƒ PBT (donor) could be significantly transferred to ESY (acceptor) via FRET process in WPP5 âŠƒ PBT-ESY nanoparticles. Notably, the antenna effect (AEWPP5⊃PBT-ESY) of WPP5 âŠƒ PBT-ESY LHS was determined to be 30.3, which was much higher than that of recent artificial LHSs for photocatalytic cross-coupling dehydrogenation (CCD) reactions, suggesting a potential application in photocatalytic reaction. Furthermore, through the energy transfer from PBT to ESY, the absolute fluorescence quantum yields performed a remarkable increase from 14.4% (for WPP5 âŠƒ PBT) to 35.7% (for WPP5 âŠƒ PBT-ESY), further confirming their FRET processes in WPP5 âŠƒ PBT-ESY LHS. Subsequently, in order to output the harvested energy for catalytic reactions, WPP5 âŠƒ PBT-ESY LHSs were used as photosensitizers to catalyze the CCD reaction of benzothiazole and diphenylphosphine oxide. Compared to free ESY group (21%), a significant cross-coupling yield of 75% in WPP5 âŠƒ PBT-ESY LHS was observed, because more UV region energy of PBT was transferred to ESY for CCD reaction, which suggested more potential in improving the catalytic activity of organic pigment photosensitizers in aqueous systems.

Influenza vaccination reveals sex dimorphic imprints of prior mild COVID-19.

Acute viral infections can have durable functional impacts on the immune system long after recovery, but how they affect homeostatic immune states and responses to future perturbations remain poorly understood1-4. Here we use systems immunology approaches, including longitudinal multimodal single-cell analysis (surface proteins, transcriptome and V(D)J sequences) to comparatively assess baseline immune statuses and responses to influenza vaccination in 33 healthy individuals after recovery from mild, non-hospitalized COVID-19 (mean, 151 days after diagnosis) and 40 age- and sex-matched control individuals who had never had COVID-19. At the baseline and independent of time after COVID-19, recoverees had elevated T cell activation signatures and lower expression of innate immune genes including Toll-like receptors in monocytes. Male individuals who had recovered from COVID-19 had coordinately higher innate, influenza-specific plasmablast, and antibody responses after vaccination compared with healthy male individuals and female individuals who had recovered from COVID-19, in part because male recoverees had monocytes with higher IL-15 responses early after vaccination coupled with elevated prevaccination frequencies of 'virtual memory'-like CD8+ T cells poised to produce more IFNγ after IL-15 stimulation. Moreover, the expression of the repressed innate immune genes in monocytes increased by day 1 to day 28 after vaccination in recoverees, therefore moving towards the prevaccination baseline of the healthy control individuals. By contrast, these genes decreased on day 1 and returned to the baseline by day 28 in the control individuals. Our study reveals sex-dimorphic effects of previous mild COVID-19 and suggests that viral infections in humans can establish new immunological set-points that affect future immune responses in an antigen-agnostic manner.

A multifunctional chemical linker in a buried interface for stable and efficient planar perovskite solar cells.

The buried interface between a perovskite (PVK) light absorbing layer and an electron transport layer (ETL) plays an utmost important role in further improving the efficiency and stability of planar perovskite solar cells (PSCs). The interfacial properties greatly affect charge transport, perovskite crystal growth, and device stability. Herein, a variable structure broad-spectrum UV-284 absorber agent 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid (HMBS) is introduced into PSCs based on SnO2 ETLs as an efficient multifunctional chemical linker to modify the buried interface properties. HMBS used to modify SnO2 can simultaneously suppress the surface trap states of ETLs, optimize the ETL/PVK interface energy level arrangement, and improve the crystallization quality of the upper perovskite films. Meanwhile, as an efficient UV absorber, HMBS can also greatly reduce the damage caused by UV light to perovskite films and thus improve the stability of devices. Consequently, HMBS-modified PSCs exhibit champion efficiencies of 23.42% (0.09 cm2) and 20.63% (1.00 cm2) along with remarkably enhanced UV stability. This work emphasizes the importance of appropriate interface treatment strategies for buried interface modification and provides an effective method for fabricating efficient and UV resistant perovskite photovoltaic devices.

Orthogonal Design of Supramolecular Prodrug Vesicles via Water-Soluble Pillar[5]arene and Betulinic Acid Derivative for Dual Chemotherapy.

Supramolecular prodrug vesicles with efficient property for dual chemotherapy have been successfully constructed based on the orthogonal self-assembly between a water-soluble pillar[5]arene host (WP5) and a betulinic acid guest (BA-D) as well as doxorubicin (DOX). Under the acidic microenvironment of cancer cells, both the encapsulated anticancer drug DOX and prodrug BA-D can be effectively released from DOX-loaded WP5⊃BA-D prodrug vesicles for combinational chemotherapy. Furthermore, bioexperiments indicate that DOX-loaded prodrug vesicles can obviously enhance the anticancer efficiency based on the cooperative effect of DOX and BA-D, while remarkably reducing the systematic toxicity in tumor-mice, displaying great potential applications in combinational chemotherapy for cancer treatments.

Influenza vaccination and single cell multiomics reveal sex dimorphic immune imprints of prior mild COVID-19.

Viral infections can have profound and durable functional impacts on the immune system. There is an urgent need to characterize the long-term immune effects of SARS-CoV-2 infection given the persistence of symptoms in some individuals and the continued threat of novel variants. Here we use systems immunology, including longitudinal multimodal single cell analysis (surface proteins, transcriptome, and V(D)J sequences) from 33 previously healthy individuals after recovery from mild, non-hospitalized COVID-19 and 40 age- and sex-matched healthy controls with no history of COVID-19 to comparatively assess the post-infection immune status (mean: 151 days after diagnosis) and subsequent innate and adaptive responses to seasonal influenza vaccination. Identification of both sex-specific and -independent temporally stable changes, including signatures of T-cell activation and repression of innate defense/immune receptor genes (e.g., Toll-like receptors) in monocytes, suggest that mild COVID-19 can establish new post-recovery immunological set-points. COVID-19-recovered males had higher innate, influenza-specific plasmablast, and antibody responses after vaccination compared to healthy males and COVID-19-recovered females, partly attributable to elevated pre-vaccination frequencies of a GPR56 expressing CD8+ T-cell subset in male recoverees that are "poised" to produce higher levels of IFNγ upon inflammatory stimulation. Intriguingly, by day 1 post-vaccination in COVID-19-recovered subjects, the expression of the repressed genes in monocytes increased and moved towards the pre-vaccination baseline of healthy controls, suggesting that the acute inflammation induced by vaccination could partly reset the immune states established by mild COVID-19. Our study reveals sex-dimorphic immune imprints and in vivo functional impacts of mild COVID-19 in humans, suggesting that prior COVID-19, and possibly respiratory viral infections in general, could change future responses to vaccination and in turn, vaccines could help reset the immune system after COVID-19, both in an antigen-agnostic manner.

Dual Functions of Performance Improvement and Lead Leakage Mitigation of Perovskite Solar Cells Enabled by Phenylbenzimidazole Sulfonic Acid.

With the continuous improvement of performance of lead-based perovskite solar cells (PSCs), the potential harm of water-soluble lead ion (Pb2+ ) to environment and public health is emerging as a major obstacle to their commercialization. Herein, an amphoteric phenylbenzimidazole sulfonic acid (PBSA) that is almost insoluble in water is added to the perovskite precursor to simultaneously regulate crystallization growth, passivate defects, and mitigate lead leakage of high-performance PSCs. Through systematic research, it is found that PBSA can not only regulate the crystallization of perovskite grains to form the film, but also passivate the defects of annealed films mainly due to the strong interaction between the functional groups in PBSA and Pb2+ , which greatly improves the crystallinity and stability of perovskite films. Consequently, the highest power conversion efficiency of 23.27% is achieved in 0.09 cm2 devices and 15.31% is obtained for large-area modules with an aperture area of 19.32 cm2 , along with negligible hysteresis and improved stability. Moreover, the leakage of lead ions from unpackaged devices is effectively prevented owing to the strong coupling between PBSA molecules and water-soluble Pb2+ to form insoluble complexes in water, which is of great significance to promote the application of optoelectronic devices based on lead-based perovskite materials.

Attenuation of Circulating Trimethylamine N-Oxide Prevents the Progression of Cardiac and Renal Dysfunction in a Rat Model of Chronic Cardiorenal Syndrome.

Chronic heart failure (HF) frequently causes progressive decline in kidney function, known as cardiorenal syndrome-2 (CRS2). Current treatment options for CRS2 remain unacceptably limited. Trimethylamine-N-oxide (TMAO), a metabolite of gut microbiota, has recently been implicated in the pathogenesis of both HF and chronic kidney disease. Here we examined whether circulating TMAO is elevated in CRS2 and if so, whether attenuation of circulating TMAO would ameliorate the progression of CRS2. Sprague-Dawley rats underwent surgery for myocardial infarction (MI) or sham (week 0) followed by subtotal (5/6) nephrectomy (STNx) or sham at week 4 to induce CRS2 or control. At week 6, MI + STNx rats and control rats received vehicle or 1.0% 3,3-Dimethyl-1-butanol (DMB, a TMAO inhibitor) treatment for 8 weeks. Compared with control rats, MI + STNx rats exhibited elevated serum TMAO at week 6, which was increased further at week 14 but was attenuated by DMB treatment. MI + STNx rats showed cardiac dysfunction as assessed by echocardiography and renal dysfunction as evidenced by increased serum creatinine and urinary kidney injury molecule-1 and decreased creatinine clearance at week 6. The cardiac and renal dysfunction in MI + STNx rats was exacerbated at week 14 but was prevented by DMB treatment. Molecular and histological studies revealed myocyte hypertrophy and increases in interstitial myocardial fibrosis and gene expression of pro-hypertrophic and pro-fibrotic markers in both heart and kidney at week 14, which were accompanied by elevated gene expression of proinflammatory cytokines. The changes in molecular and histological parameters observed in MI + STNx rats were significantly reduced by DMB treatment. These findings suggest that rats with CRS2 have elevated circulating TMAO, which is associated with the exacerbation of cardiac and renal dysfunction. Attenuation of circulating TMAO can ameliorate cardiac and renal injury and prevents the progression of CRS2.

The Preparation of a Water-Soluble Phospholate-Based Macrocycle for Constructing Artificial Light-Harvesting Systems.

On the basis of cyclotrixylohydroquinoylene (CTX), a novel water-soluble phospholate-based CTX derivative (WPCTX) was prepared with facile synthetic procedure and satisfying yield. Several model guest molecules were selected to investigate WPCTX's host-guest properties. Based on the study of the host and model guest complexation, a tetraphenylethylene derivative from model guest was employed as a guest molecule (G) to form WPCTX⊃G nanoparticles (NPs) with WPCTX through further supramolecular self-assembly in water. Moreover, a hydrophobic fluorescent dye, Eosin Y(ESY) or Nile red (NiR), was encapsulated in WPCTX⊃G NPs to construct two types of artificial light-harvesting systems. Their high antenna effect demonstrated such NPs successfully mimicked light-harvesting systems in nature.

Epicutaneous Staphylococcus aureus induces IL-36 to enhance IgE production and ensuing allergic disease.

IgE induced by type 2 immune responses in atopic dermatitis is implicated in the progression of atopic dermatitis to other allergic diseases, including food allergies, allergic rhinitis, and asthma. However, the keratinocyte-derived signals that promote IgE and ensuing allergic diseases remain unclear. Herein, in a mouse model of atopic dermatitis-like skin inflammation induced by epicutaneous Staphylococcus aureus exposure, keratinocyte release of IL­36α along with IL-4 triggered B cell IgE class-switching, plasma cell differentiation, and increased serum IgE levels-all of which were abrogated in IL-36R-deficient mice or anti-IL­36R-blocking antibody-treated mice. Moreover, skin allergen sensitization during S. aureus epicutaneous exposure-induced IL-36 responses was required for the development of allergen-specific lung inflammation. In translating these findings, elevated IL­36 cytokines in human atopic dermatitis skin and in IL­36 receptor antagonist-deficiency patients coincided with increased serum IgE levels. Collectively, keratinocyte-initiated IL­36 responses represent a key mechanism and potential therapeutic target against allergic diseases.

Fabrication of porous polymer coating layers with selective wettability on filter papers via the breath figure method and their applications in oil/water separation.

A comb-like amphiphilic polymer (PBTF), composed of hydrophobic backbones and hydrophilic side chains, was employed to grow honeycomb coating layers in situ on a filter paper via directly casting a polymer solution and by the subsequent dynamic breath figure (BF) method. Through regulating the hydrophilic polymer side chain density and the solution concentration, a continuous honeycomb coating layer contouring to the filter paper surface profile, in addition to possessing a water contact angle (WCA) as high as 146°, was successfully fabricated. The present study also finds that increasing the hydrophilic side chain density will turn PBTF into a surfactant-like polymer, and thus, endow the PBTF solution with the capacity of numerous micro-nano-sized water droplets, rather than simply stabilizing the ordered water droplet arrays on the surface of the solution. With vast nano-sized water droplets in it, the once transparent PBTF solution changed into a translucent nano-emulsion, which demonstrates a strong Tyndall effect. While casting such nano-emulsion on a filter paper and then subjecting to the BF process, the polymeric solute takes both nano-emulsion intrinsic nano-sized water droplets and solvent evaporation-induced water droplets as templates and self-assembles into a bird-nest-like three-dimensional porous microstructure, which possesses micro-nano-sized communicating pores. By regulating the water content in the nano-emulsion, the bird-nest-like structure can be uniformly formed on the surface of the filter paper, which revealed a WCA of 152°. The coated filter papers possess selective wettability, and meanwhile, maintain the inherent permeability of the substrates, which therefore can be directly utilized as oil/water separation materials.

Stoichiometry-Controlled Chirality Induced by Co-assembly of Tetraphenylethylene Derivative, γ-CD, and Water-Soluble Pillar[5]arene.

A stoichiometry-controlled chirality induction was successfully achieved through coassemblies of amphiphilic tetraphenylethylene derivative TPEA, γ-cyclodextrin (γ-CD), and water-soluble pillar[5]arene WP5 in aqueous solution. Stoichiometric variation of WP5 was found to be an effective strategy to induce topological transition between the pseudo[4]rotaxane and the vesicular form. Interestingly, the formation of pseudo[4]rotaxane triggered dual chirality induction from chiral γ-CD to TPEA (negative ICD1), and then, to dynamically racemic WP5 (positive ICD2), whereas both ICD1 and ICD2 were silent in the vesicular form.

Inherited SLP76 deficiency in humans causes severe combined immunodeficiency, neutrophil and platelet defects.

The T cell receptor (TCR) signaling pathway is an ensemble of numerous proteins that are crucial for an adequate immune response. Disruption of any protein involved in this pathway leads to severe immunodeficiency and unfavorable clinical outcomes. Here, we describe an infant with severe immunodeficiency who was found to have novel biallelic mutations in SLP76. SLP76 is a key protein involved in TCR signaling and in other hematopoietic pathways. Previous studies of this protein were performed using Jurkat-derived human leukemic T cell lines and SLP76-deficient mice. Our current study links this gene, for the first time, to a human immunodeficiency characterized by early-onset life-threatening infections, combined T and B cell immunodeficiency, severe neutrophil defects, and impaired platelet aggregation. Hereby, we characterized aspects of the patient's immune phenotype, modeled them with an SLP76-deficient Jurkat-derived T cell line, and rescued some consequences using ectopic expression of wild-type SLP76. Understanding human diseases due to SLP76 deficiency is helpful in explaining the mixed T cell and neutrophil defects, providing a guide for exploring human SLP76 biology.

An efficient artificial light-harvesting system with tunable emission in water constructed from a H-bonded AIE supramolecular polymer and Nile Red.

With the aid of CTAB amphiphile, water-phase artificial light-harvesting systems were fabricated as nanoparticles by the self-assembly of two low-molecular-weight organic molecules: a UPy-functionalized TPE derivative 1 with both supramolecular polymerization and AIE capabilities as a donor and a fluorescent chromophore NiR as an acceptor. Owing to the flexibility of supramolecular self-assembly, tunable emissions including white-light emission could be easily realized with high energy transfer efficiency and the antenna effect.